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Title:
COMPOSITIONS DECREASING ACTIVITY OF HORMONE-SENSITIVE LIPASE
Document Type and Number:
WIPO Patent Application WO/2003/051842
Kind Code:
A2
Abstract:
Carbamates and related compounds of formula R1R2NCO-Y or R1R2NCS-Y wherein R1 and R2 may form a ring, are inhibitors of hormone sensitive lipase and are useful for the treatment of any disorder where it is desirable to modulate the plasma level of free fatty acids, glycerol, LDL-cholesterol, HDL-cholesterol, insulin and/or glucose; and or modulate intracellular triacylglycerol and cholesterol stores, intracellular level of fatty acids, fatty acid esters such as diacylglycerols, phosphatidic acids, long chain acyl-CoA’s as well as citrate or malonyl-CoA; and or increase insulin sensitivity; and or modulate insulin secretion from pancreatic beta cells. More particularly said disorders are selected from the group consisting of insulin resistance, diabetes type 1, hyperglycemia, dislipidemia, obesity, abnormalities of lipoprotein metabolism and any combinations thereof.

Inventors:
EBDRUP SOEREN
HANSEN HOLGER CLAUS
VEDSOE PER
CORNELIS DE JONG JOHANNES
JACOBSEN POUL
Application Number:
PCT/DK2002/000853
Publication Date:
June 26, 2003
Filing Date:
December 13, 2002
Export Citation:
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Assignee:
NOVO NORDISK AS (DK)
International Classes:
C07D249/08; A61K31/16; A61K31/27; A61K31/275; A61K31/341; A61K31/343; A61K31/352; A61K31/37; A61K31/381; A61K31/40; A61K31/401; A61K31/4015; A61K31/4035; A61K31/4045; A61K31/407; A61K31/41; A61K31/415; A61K31/4155; A61K31/4164; A61K31/4184; A61K31/4192; A61K31/4196; A61K31/423; A61K31/426; A61K31/428; A61K31/437; A61K31/44; A61K31/4402; A61K31/4406; A61K31/4409; A61K31/4439; A61K31/444; A61K31/445; A61K31/451; A61K31/4545; A61K31/455; A61K31/465; A61K31/47; A61K31/4709; A61K31/472; A61K31/4725; A61K31/473; A61K31/495; A61K31/496; A61K31/498; A61K31/4995; A61K31/50; A61K31/505; A61K31/5375; A61K31/5377; A61K31/541; A61K31/55; A61K31/551; A61K31/63; A61K45/00; A61P1/04; A61P1/18; A61P3/04; A61P3/06; A61P3/10; A61P5/50; A61P9/04; A61P9/06; A61P9/10; A61P9/12; A61P17/06; A61P21/04; A61P25/16; A61P25/22; A61P25/24; A61P25/28; A61P27/02; A61P29/00; A61P31/04; A61P31/18; A61P35/00; A61P43/00; C07C39/367; C07C233/25; C07C233/26; C07C233/60; C07C269/00; C07C271/58; C07C275/34; C07C303/34; C07C303/38; C07C307/06; C07C311/04; C07C311/17; C07C311/21; C07C311/29; C07C311/40; C07C317/22; C07C323/20; C07D207/325; C07D207/36; C07D207/40; C07D207/404; C07D209/08; C07D209/32; C07D209/48; C07D211/40; C07D211/88; C07D213/61; C07D213/63; C07D213/64; C07D213/643; C07D213/65; C07D213/68; C07D213/69; C07D213/70; C07D213/74; C07D213/75; C07D213/82; C07D213/84; C07D215/14; C07D215/20; C07D215/22; C07D217/06; C07D217/24; C07D221/14; C07D231/12; C07D231/14; C07D231/16; C07D231/18; C07D233/54; C07D233/60; C07D233/70; C07D233/84; C07D235/18; C07D235/26; C07D237/14; C07D239/22; C07D239/34; C07D239/38; C07D241/18; C07D241/44; C07D249/04; C07D249/12; C07D249/18; C07D253/04; C07D257/04; C07D261/12; C07D261/20; C07D263/52; C07D277/20; C07D277/24; C07D277/34; C07D277/68; C07D285/00; C07D285/01; C07D295/18; C07D295/20; C07D295/205; C07D295/26; C07D307/16; C07D307/28; C07D307/52; C07D307/89; C07D311/16; C07D311/18; C07D333/16; C07D333/32; C07D333/34; C07D333/40; C07D401/04; C07D401/12; C07D401/14; C07D403/12; C07D405/12; C07D405/14; C07D409/04; C07D409/12; C07D413/12; C07D417/12; C07D471/04; C07D471/06; C07D487/08; C07D487/18; C07D491/10; C07D513/04; C07D521/00; (IPC1-7): C07D213/00
Domestic Patent References:
WO2000069810A12000-11-23
WO2002020483A12002-03-14
WO2002006189A22002-01-24
WO1999062870A11999-12-09
WO2002038153A12002-05-16
WO2001021584A12001-03-29
WO2000063208A12000-10-26
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WO2000054759A22000-09-21
WO2001021602A12001-03-29
WO2002012210A12002-02-14
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WO2001047923A12001-07-05
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Foreign References:
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Other References:
DATABASE WPI Section Ch, Week 199709 Derwent Publications Ltd., London, GB; Class B03, AN 1997-100136 XP002230558 & WO 97/01533 A (GREEN CROSS CORP) 16 January 1997 (1997-01-16)
SCHMIDT F ET AL: "Glucuronide prodrugs of hydroxy compounds for antibody directed enzyme prodrug therapy (adept): a phenol nitrogen mustard carbamate" BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, OXFORD, GB, vol. 7, no. 8, 22 April 1997 (1997-04-22), pages 1071-1076, XP004136187 ISSN: 0960-894X
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Claims:
CLAIMS
1. Use of a compound of the general formula I wherein R'is selected from hydrogen, C16alkyl, C26alkenyl and C310cycloalkyl, each of which is optionally substituted with one or more substituents independently selected from hy droxy, sulfanyl, oxo, halogen, amino, cyano and nitro; and R2 is selected from C16alkyl, C26alkenyl, aryl, heteroaryl, C38heterocyclyl and C310 cycloalkyl, each of which is optionally substituted with one or more substituents independ ently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C16alkyl, C26 alkenyl, aryl, heteroaryl, C38heterocyclyl and C310cycloalkyl, wherein each of hydroxy, sul fanyl, sulfo, amino, C16alkyl, C26alkenyl, aryl, heteroaryl, C38heterocyclyl and C310 cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C16alkyl, C26alkenyl, aryl, heteroaryl, C38heterocyclyl and C3 10cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C16alkyl, C26alkenyl, aryl, heteroaryl, C38heterocyclyl and C310cycloalkyl is op tionally substituted with one or more substituents independently selected from hydroxy, sul fanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1 6alkyl, C2. 6alkenyl, aryl, heteroaryl, C3 8 heterocyclyl and C310cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1 6alkyl, C26alkenyl, aryl, heteroaryl, C38heterocyclyl andC3locycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C16alkyl, C26alkenyl, aryl, heteroaryl, C38heterocyclyl and C3 cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1 6alkyl, C2 6alkenyl, aryl, heteroaryl, C38heterocyclyl and C3 10cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1 6alkyl, C2 6alkenyl, perhalomethyl and perhalomethoxy ; and wherein R2 is optionally covalently bound to R'by an ether, thioether, CC or CN bond, to form a ring system with the Natom to which R'and R2 are bound; and X is O or S ; and L is a group such thatC (=X) L is a hydrolysable group; or a pharmaceutical acceptable salt thereof, or a pharmaceutical acceptable solvate thereof, or any tautomeric forms, stereoisomers, mixture of stereoisomers including a racemic mix ture, or polymorphs for inhibition of the lipolytic activity of hormonesensitive lipase against triacylglycerols, dia cylglycerols, cholesterol acyl esters or steroid acyl esters.
2. Use of a compound of the general formula I wherein R'is selected from hydrogen, C1 6alkyl, C2 6alkenyl and C3 10cycloalkyl, each of which is optionally substituted with one or more substituents independently selected from hy droxy, sulfanyl, oxo, halogen, amino, cyano and nitro; and R2 is selected from C16alkyl, C26alkenyl, aryl, heteroaryl, C38heterocyclyl and C3 10 cycloalkyl, each of which is optionally substituted with one or more substituents independ ently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C16alkyl, C26 alkenyl, aryl, heteroaryl, C38heterocyclyl and C310cycloalkyl, wherein each of hydroxy, sul fanyl, sulfo, amino, C16alkyl, C26alkenyl, aryl, heteroaryl, C38heterocyclyl and C3 10 cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1 6alkyl, C26alkenyl, aryl, heteroaryl, C3 8heterocyclyl and C3 10cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C16alkyl, C26alkenyl, aryl, heteroaryl, C38heterocyclyl and C3 10cycloalkyl is op tionally substituted with one or more substituents independently selected from hydroxy, su I fanyl, sulfo, oxo, halogen, amino, cyano, nitro, C16alkyl, C26alkenyl, aryl, heteroaryl, C38 heterocyclyl and C310cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C16alkyl, C2 6alkenyl, aryl, heteroaryl, C3 8heterocyclyl and C3 10cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C16alkyl, C26alkenyl, aryl, heteroaryl, C38heterocyclyl and C3 10cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1 6alkyl, C2 6alkenyl, aryl, heteroaryl, C3 8heterocyclyl and C3 10cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1 6alkyl, C2 6alkenyl, perhalomethyl and perhalomethoxy ; and wherein R2 is optionally covalently bound to R'by an ether, thioether, CC or CN bond, to form a ring system with the Natom to which R'and R2 are bound; and X is O or S; and L is a group such thatC (=X) L is a hydrolysable group; or a pharmaceutically acceptable salt thereof, or a pharmaceutical acceptable solvate thereof, or any tautomeric forms, stereoisomers, mixture of stereoisomers including a racemic mix ture, or polymorphs for the preparation of a medicament for the treatment of any disorder where it is desirable to modulate the plasma level of free fatty acids, glycerol, LDLcholesterol, HDLcholesterol, in sulin and/or glucose ; and/or modulate intracellular triacylglycerol and cholesterol ester stores, intracellular level of fatty acids, fatty acid esters such as diacylglycerols, phosphatidic acids, long chain acylCoA's as well as citrate or malonylCoA ; and/or increase insulin sensitivity in adipose tissue, skeletal muscle, liver or pancreatic ß cells ; and/or modulate insulin secretion from pancreatic 3 cells.
3. Use of a compound of the general formula I according to claim 1 for the preparation of a pharmaceutical medicament.
4. Use of a compound of the general formula (I) according to claim 1 for the preparation of a medicament for the treatment of insulin resistance, diabetes type 1, diabetes type 2, meta bolic syndrome X, impaired glucose tolerance, hyperglycemia, dyslipidemia, obesity, abnor malities of lipoprotein metabolism and any combination thereof.
5. The use according to any one of claims 14, wherein X is O.
6. The use according to any one of claims 15, wherein the group L comprises an O, via which L is bound to the C in formula (I).
7. The use according to any one of claims 15, wherein the group L comprises a N, via which L is bound to the C in formula (I).
8. The use according to any one of claims 15, wherein the group L is selected from the group consisting of wherein Y is O or S; and Ra1, Ra2, Ra3, Ra4, Ra5 and Ra6 are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C16alkyl, C26alkenyl, aryl, heteroaryl, C38heterocyclyl, or C3 10cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C16alkyl, C26alkenylalkyl, aryl, heteroaryl, C3$heterocyclyl and C3 1ocycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C16alkyl, C26alkenyl, aryl, heteroaryl, C3_8heterocyclyl and C310cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C16alkyl, C26alkenyl, aryl, heteroaryl, C38 heterocyclyl and C310cycloalkyl is optionally substituted with one or more substituents inde pendently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C16alkyl, C26alkenyl, aryl, heteroaryl, C3$heterocyclyl and C310cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, Cl6alkyl, C26alkenyl, aryl, heteroaryl, C38heterocyclyl and C310 cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C16alkyl, C26alkenyl, aryl, heteroaryl, C38heterocyclyl and C31ocYcloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, Cl6alkyl, C26alkenyl, aryl, heteroaryl, C3$heterocyclyl and C31ocycloalkyl is op tionally substituted with one or more substituents independently selected from hydroxy, sul fanyl, sulfo, oxo, halogen, amino, cyano, nitro, C16alkyl, C26alkenyl, perhalomethyl and perhalomethoxy.
9. The use according to claim 8, wherein at least one of Ra1, Ra2, Ra3, Ra4, Ra5 and Ra6 is F.
10. The use according to any one of claims 16, wherein the group L is an optionally substi tutedOphenyl, via which L is bound to the C in formula (I).
11. The use according to any one of claims 110, wherein R'and R2 are covalently bound to each other so that the group R'NR2forms a piperazine, said piperazine being bound to the C in formula (I).
12. The use according to any one of claims 110, wherein R1 and R2 are covalently bound to each other so that the group R'NR2 forms a piperidine, said piperidine being bound to the C in fornula (I).
13. The use according to any one of claims 110, wherein R'is selected from the group con sisting of C16alkyl, C26alkenyl and C310cycloalkyl, each of which is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano and nitro.
14. The use according to any one of claims 110, wherein R'is methyl.
15. The use according to any one of claims 110, wherein R2 is phenyl.
16. The use according to any one of claims 110, wherein R2 is a heteroaryl.
17. The use according to any one of claims 110, wherein R'is methyl and R2 is phenyl.
18. The use according to any one of claims 16, wherein the group L is an optionally substi tutedOphenyl via which L is bound to the C in formula (I), and R'and R2 are covalently bound to each other so that the group R'NR2 forms a piperazine, said piperazine being bound to the C in fornula (I).
19. The use according to any one of claims 16, wherein the group L is an optionally substi tutedOphenyl via which L is bound to the C in formula (I), and R, and W are covalently bound to each other so that the group R'NR2 forms a piperidine, said piperidine being bound to the C in fornula (I).
20. The use according to any one of claims 16, wherein the group L is an optionally substi tutedOphenyl via which L is bound to the C in formula (I), and R'is methyl and R is phenyl.
21. The use according to any one of claims 120, wherein pKa of the group L is between 4 and 12, between 6 and 12, between 7 and 12, between 8 and 12, preferably between 8.5 to 11. 5, and most preferable between 9.0 to 11.0.
22. The use according to any one of claims 121, wherein administration of said compound is by the oral route.
23. The use according to any one of claims 121, wherein administration of said compound is by the nasal, transdermal, pulmonal, or parenteral route.
24. A method of treating any disorder where it is desirable to inhibit the lipolytic activity of hormonesensitive lipase against triacylglycerols, diacylglycerols, cholesterol acyl esters or steroid acyl esters, wherein said method comprises the use according to any one of claims 1 23.
25. A method of treating any disorder where it is desirable to modulate the plasma level of free fatty acids or to modulate the handling, storage and oxidation of intracellular fatty acid and cholesterol, wherein said method comprises the use according to any one of claims 1 23.
26. The method according to any one of claims 2425, wherein said disorder is selected from the group consisting of insulin resistance, diabetes type 1, diabetes type 2, metabolic syn drome X, impaired glucose tolerance, hyperglycemia, dyslipidemia, obesity, abnormalities of lipoprotein metabolism and any combination thereof.
27. A pharmaceutical composition comprising a compound of formula I wherein R'is selected from hydrogen, C14alkyl, C26alkenyl and C3 10cycloalkyl, each of which is optionally substituted with one or more substituents independently selected from hy droxy, sulfanyl, oxo, halogen, amino, cyano and nitro; and R2 is selected from C16alkyl, C26alkenyl, aryl, heteroaryl, C38heterocyclyl and C310 cycloalkyl, each of which is optionally substituted with one or more substituents independ ently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C16alkyl, C26 alkenyl, aryl, heteroaryl, C38heterocyclyl and C310cycloalkyl, wherein each of hydroxy, sul fanyl, sulfo, amino, C16alkyl, C26alkenyl, aryl, heteroaryl, C38heterocyclyl and C310 cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C14alkyl, C26alkenyl, aryl, heteroaryl, C3heterocyclyl and C3 10cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, Cl6alkyl, C26alkenyl, aryl, heteroaryl, C38heterocyclyl andC3locycloalkyl is op tionally substituted with one or more substituents independently selected from hydroxy, sul fanyl, sulfo, oxo, halogen, amino, cyano, nitro, C16alkyl, C26alkenyl, aryl, heteroaryl, C38 heterocyclyl and C3 10cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1 6alkyl, C26alkenyl, aryl, heteroaryl, C3$heterocyclyl and C3 1ocycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C_6alkyl, C2alkenyl, aryl, heteroaryl, C38heterocyclyl and Cs cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1 6alkyl, C24alkenyl, aryl, heteroaryl, C3 8heterocyclyl and C3 10cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C16alkyl, C26alkenyl, perhalomethyl and perhalomethoxy ; and wherein R2 is optionally covalently bound to R'by an ether, thioether, CC or CN bond, to form a ring system with the Natom to which R'and R2 are bound; and X is O or S; and L is a group such thatC (=X) L is a hydrolysable group; or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof, or any tautomeric forms, stereoisomers, mixture of stereoisomers including a racemic mix ture, or polymorphs.
28. The pharmaceutical composition according to claim 27, wherein X is O.
29. The pharmaceutical composition according to any one of claims 2728, wherein the group L comprises an O, via which L is bound to the C in formula (I).
30. The pharmaceutical composition according to any one of claims 2728, wherein the group L comprises a N, via which L is bound to the C in formula (I).
31. The pharmaceutical composition according to any one of claims 2729, wherein the group L is selected from the group consisting of wherein Y is O or S; and Ra1, Ra2, Ra3, Ra4, Ra5 and Ras are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C16alkyl, C26alkenyl, aryl, heteroaryl, C38heterocyclyl, or C3 10cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C16alkyl, C26alkenyl, aryl, heteroaryl, C34heterocyclyl and C310cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, Cl6alkyl, C26alkenyl, aryl, heteroaryl, C38heterocyclyl and C310cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C16alkyl, C26alkenyl, aryl, heteroaryl, C38 heterocyclyl and C310cycloalkyl is optionally substituted with one or more substituents inde pendently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C16alkyl, C26alkyl, aryl, heteroaryl, C38heterocyclyl and C310cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C16alkyl, C26alkenyl, aryl, heteroaryl, C38heterocyclyl and C310 cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C16alkyl, C26alkenyl, aryl, heteroaryl, C34heterocyclyl and C310cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C16alkyl, C26alkenyl, aryl, heteroaryl, C38heterocyclyl and C310cycloalkyl is op tionally substituted with one or more substituents independently selected from hydroxy, sul fanyl, sulfo, oxo, halogen, amino, cyano, nitro, C16alkyl, C24alkenyl, perhalomethyl and perhalomethoxy.
32. The pharmaceutical composition according to claim 31, wherein at least one of Ra1, Ra2, Ra3, Ra4 Ra5 and Ras is F.
33. The pharmaceutical composition according to any one of claims 2729, wherein the group L is an optionally substitutedOphenyl, via which L is bound to the C in formula (I).
34. The pharmaceutical composition according to any one of claims 2733, wherein R'and R2 are covalently bound to each other so that the group R'NR2 forms a piperazine, said piperazine being bound to the C in fornula (I).
35. The pharmaceutical composition according to any one of claims 2733, wherein R'and R2 are covalently bound to each other so that the group R'NR2forms a piperidine, said piperidine being bound to the C in fornula (I).
36. The pharmaceutical composition according to any one of claims 2733, wherein R'is se lected from the group consisting of C16alkyl, C26alkenyl and C310cycloalkyl, each of which is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano and nitro.
37. The pharmaceutical composition according to any one of claims 2733, wherein R'is methyl.
38. The pharmaceutical composition according to any one of claims 2733, wherein R2 is phenyl.
39. The pharmaceutical composition according to any one of claims 2733, wherein R2 is a heteroaryl.
40. The pharmaceutical composition according to any one of claims 2733, wherein R'is methyl and R2 is phenyl.
41. The pharmaceutical composition according to any one of claims 2729, wherein the group L is an optionally substitutedOphenyl via which L is bound to the C in formula (I), and R1 and R2 are covalently bound to each other so that the group R1NR2 forms a piperazine, said piperazine being bound to the C in fornula (I).
42. The pharmaceutical composition according to any one of claims 2729, wherein the group L is an optionally substitutedOphenyl via which L is bound to the C in formula (I), and R1 and R2 are covalently bound to each other so that the group R'NR forms a piperidine, said piperidine being bound to the C in fornula (I).
43. The pharmaceutical composition according to any one of claims 2729, wherein the group L is an optionally substitutedOphenyl via which L is bound to the C in formula (I), and R'is methyl and R2 is phenyl.
44. The pharmaceutical composition according to any one of claims 2743, wherein pKa of the group L is between 4 and 12, between 6 and 12, between 7 and 12, between 8 and 12, preferably between 8.5 to 11.5, and most preferable between 9.0 to 11.0.
45. The pharmaceutical composition according to any one of claims 2744, which is for oral administration.
46. The pharmaceutical composition according to any one of claims 2744, which is for administration by the nasal, transdermal, pulmonal, or parenteral route.
Description:
USE OF COMPOUNDS FOR DECREASING ACTIVITY OF HORMONE-SENSITIVE Li- PASE.

FIELD OF THE INVENTION The present invention relates to compounds, compositions containing them, and their use for treating medical disorders where it is desirable to modulate the activity of hor- mone-sensitive lipase.

BACKGROUND OF THE INVENTION The overall energy homeostasis of a mammalian system requires a high degree of regulation to ensure the availability of the appropriate substrate at the appropriate time. Plasma glucose levels rise during the post-prandial state, to return to pre-prandial levels within 2-3 hours.

During these 2-3 hours, insulin promotes glucose uptake by skeletal muscle and adipose tis- sue and decreases the release of free fatty acids (FFA) from adipocytes, to ensure that the two substrates do not compete with each other. When plasma glucose levels fall, an eleva- tion in plasma FFA is necessary to switch from glucose to fat utilization by the various tis- sues.

In individuals with insulin resistance, FFA levels do not fall in response to insulin, as they do in normal individuals, preventing the normal utilization of glucose by skeletal muscle, adipose and liver. Furthermore, there is a negative correlation between insulin sensitivity and plasma FFA levels.

Hormone-sensitive lipase (HSL) is an enzyme, expressed primarily in adipocytes, that ca- talyses the conversion of triglycerides to glycerol and fatty acids. It is through the regulation of this enzyme that the levels of circulating FFA are modulated. Insulin leads to the inactiva- tion of HSL with a subsequent fall in plasma FFA levels during the post-prandial state, fol- lowed by the activation of the enzyme when the insulin concentration falls and catechola- mines rise during the post-absorptive period. The activation of HSL leads to an increase in plasma FFA, as they become the main source of energy during fasting.

The activation-inactivation of HSL is primarily mediated through the cAMP-protein kinase A and AMP-dependent kinase pathways. There are compounds like nicotinic acid and its de- rivatives, that decrease the activation of HSL via these pathways and cause a decrease in lipolysis that leads to a reduction in the FFA levels. These drugs have a beneficial effect in the utilization of glucose and in the normalization of the excess triglyceride synthesis seen in patients with elevated FFA. However, since these pathways are used by other processes in the body, these drugs have severe side effects.

We have found compounds that specifically inhibit the lipolytic activity of HSL and lead to a decrease in plasma FFA levels. These compounds can be used to treat disorders where a decreased level of plasma FFA is desired, such as insulin resistance, syndrome X, dyslipi- demia, abnormalities of lipoprotein metabolism.

One object of the present invention is to provide compounds and pharmaceutical composi- tions that inhibit the lipolytic activity of HSL. A further object is to provide compounds which have good pharmaceutical properties such as solubility, bioavailability etc.

DEFINITIONS The following is a detailed definition of the terms used to describe the compounds of the invention.

"Halogen"designates an atom selected from the group consisting of F, Cl, Br and 1.

The term"C14-alkyl"in the present context designates a saturated, branched or straight hydro- carbon group having from 1 to 6 carbon atoms. Representative examples include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, iso- pentyl, neopentyl, tert-pentyl, n-hexyl, isohexyl and the like.

The term"C24-alkyl"in the present context designates a saturated, branched or straight hydro- carbon group having from 2 to 6 carbon atoms. Representative examples include, but are not limited to, ethyl, n-propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, tert-pentyl, n-hexyl, isohexyl and the like.

The term"C1-alkoxy"in the present context designates a group 4-C14-alkyl wherein Cl-6-alkyl is as defined above. Representative examples include, but are not limited to, methoxy, eth- oxy, n-propoxy, isopropoxy, butoxy, isobutoxy, sec-butoxy, tert-butoxy, n-pentoxy, isopen- toxy, neopentoxy, tert-pentoxy, n-hexoxy, isohexoxy and the like.

The term"Cm-alkoxy'in the present context designates a group-0-CI-6-alkyl wherein Cl-alkyl is a saturated, branched or straight hydrocarbon group having from 3-6 carbon atoms. Repre- sentative examples of C3-alkoxy include, but are not limited to, n-propoxy, isopropoxy, bu- toxy, isobutoxy, sec-butoxy, tert-butoxy, n-pentoxy, isopentoxy, neopentoxy, tert-pentoxy, n- hexoxy, isohexoxy and the like.

The term"C24-alkenyl"as used herein, represent an olefinically unsaturated branched or straight hydrocarbon group having from 2 to 6 carbon atoms and at least one double bond.

Examples of such groups include, but are not limited to, vinyl, 1-propenyl, 2-propenyl, allyl, iso-propenyl, 1, 3-butadienyl, 1-butenyl, hexenyl, pentenyl and the like.

The term "C3-10-cycloalkyl" as used herein represents a saturated mono-, bi-, tri-or spirocar- bocyclic group having from 3 to 10 carbon atoms. Representative examples are cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclononyl, cyclodecyl, bicy- do [3.2. 1] octyl, spiro [4.5] decyl, norpinyl, norbonyl, norcaryl, adamantyl and the like.

The term"C34-heterocyclyl"as used herein represents a saturated 3 to 8 membered ring containing one or more heteroatoms selected from nitrogen, oxygen and sulfur. Representa- tive examples are pyrrolidyl, piperidyl, piperazinyl, morpholinyl, thiomorpholinyl, aziridinyl, tetrahydrofuranyl and the like.

The term"aryl"as used herein represents a carbocyclic aromatic ring system being either monocyclic, bicyclic, or polycyclic, such as phenyl, biphenyl, naphthyl, anthracenyl, phenan- threnyl, fluorenyl, indenyl, pentalenyl, azulenyl, biphenylenyl and the like. Aryl is also in- tended to include the partially hydrogenated derivatives of the carbocyclic aromatic systems enumerated above. Non-limiting examples of such partially hydrogenated derivatives are 1,2, 3, 4-tetrahydronaphthyl, 1, 4-dihydronaphthyl and the like.

The term"aryloxy"as used herein represents an aryl which is linked via an oxygen atom, e. g. phenoxy, 1-naphthyloxy, 2-naphthyloxy and the like.

The term"heteroaryl"as used herein represents a heterocyclic aromatic ring system contain- ing one or more heteroatoms selected from nitrogen, oxygen and sulfur such as furyl, thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, isoxazolyl, isothiazolyl, 1,2, 3-triazolyl, 1,2, 4-triazolyl, pyranyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, 1,2, 3-triazinyl, 1,2, 4-triazinyl, 1,3, 5- triazinyl, 1,2, 3-oxadiazolyl, 1,2, 4-oxadiazolyl, 1,2, 5-oxadiazolyl, 1,3, 4-oxadiazolyl, 1,2, 3-thiadiazolyl, 1,2, 4-thiadiazolyl, 1,2, 5-thiadiazolyl, 1,3, 4-thiadiazolyl, tetrazolyl, thiadiazinyl, indolyl, isoindolyl, benzofuranyl, benzothiophenyl (thianaphthenyl), indazolyl, benzimidazolyl, benzthiazolyl, ben- zisothiazolyl, benzoxazolyl, benzisoxazolyl, purinyl, quinazolinyl, quinolizinyl, quinolinyl ; iso- quinolinyl, quinoxalinyl, naphthyridinyl, pteridinyl, carbazolyl, azepinyl, diazepinyl, acridinyl and the like. Heteroaryl is also intended to include the partially hydrogenated derivatives of the heterocyclic systems enumerated above. Non-limiting examples of such partially hydro- genated derivatives are 2, 3-dihydrobenzofuranyl, 3, 4-dihydroisoquinolinyl, pyrrolinyl, pyra- zolinyl, indolinyl, oxazolidinyl, oxazolinyl, oxazepinyl and the like.

The term"perhalomethyl"as used herein designates a methyl moiety substituted with three halogen atoms. Non-limiting examples of perhalomethyl are CF3, CCI3, and CF2CI.

The term"perhalomethoxy"as used herein designates a perhalomethyl linked via an oxygen atom, e. g.-O-CF3,-O-CCI3, and-O-CF2CI The term"ring system"as used herein includes aromatic as well as non-aromatic ring moieties, which may be monocyclic, bicyclic or polycyclic, and they encompass moieties with zero, one or more hetereatoms selected from nitrogen, oxygen and sulphur. Non-limiting examples of such ring systems are aryl, C3-8-heterocyclyl and heteroaryl.

The term"heterocyclic system"as used herein includes aromatic as well as non-aromatic ring moieties, which may be monocyclic, bicyclic or polycyclic, and containing in their ring structure one or more heteroatoms selected from nitrogen, oxygen and sulfur. Non-limiting examples of such heterocyclic systems are C3 8-heterocyclyl and heteroaryl.

Certain of the above defined terms may occur more than once in the structural formulae, and upon such occurrence each term shall be defined independently of the other.

The term"optionally substituted"as used herein means that the groups in question are either unsubstituted or substituted with one or more of the substituents specified. When the groups in question are substituted with more than one substituent the substituents may be the same or different.

The term"optionally covalently bound"as used herein means that the substituents in ques- tion are either not covalently bound to each other or the substituents are directly connected to each other by a covalent bond. A non-limiting example of such optionally covalently bound substituents is-NR1R2 wherein R1 is ethyl and R2 is propyl which provided that the substitu- ents, ethyl and propyl, are optionally covalently bound may be ethyl-propyl-amino, 1- piperidyl, 3-methyl-1-pyrrolidyl or 2, 3-dimethyl-1-azetidyl.

The term"hydrolysable group"as used herein means a group which can be hydrolyse at certain chemical conditions, i. e. an internal covalent bond in the group can be cleaved to give two compounds. A hydrolysable group does not have to be hydrolyse during carrying out the present invention. For instance, the hydrolysable group-C (=X) -L can be hydrolyse to give the products-C (=X) OH and HL, which means that the covalent bond between-C (X) and L is cleaved. Examples of hydrolysable groups are carbamates, esters and amides.

The terms"disease","condition"and"disorder"as used herein are used interchangeably to specifiy a state of a patient which is not the normal physiological state of man.

The term"treatment"as used herein means the management and care of a patient having developed a disease, condition or disorder, as well as the management and care of an indi- vidual at risk of developing the disease, condition or disorder prior to the clinical onset of said disease, condition or disorder. The purpose of treatment is to combat the disease, condition or disorder, as well as to to combat the development of the disease, condition or disorder.

Treatment includes the administration of the active compounds to prevent or delay the onset of the symptoms or complications and to eliminate or control the disease, condition or disor- der as well as to alleviate the symptoms or complications associated with the disease, condi- tion or disorder.

The term"effective amount"as used herein means a dosage which is sufficient in order for the treatment of the patient to be effective compared with no treatment.

The term"modulate"as used herein means to influence, i. e. to modulate a parameter means to influence that parameter in a desired way. Examples are to modulate insulin secretion from beta cells and to modulate the plasma level of free fatty acids.

The term"medicament"as used herein means a pharmaceutical composition suitable for administration of the pharmaceutical active compound to a patient.

The term"pharmaceutically acceptable"as used herein means suited for normal pharmaceu- tical applications, i. e. giving rise to no adverse events in patients etc.

DESCRIPTION OF THE INVENTION The present invention relates to the use of a compound of the general formula I wherein R'is selected from hydrogen, C1-6-alkyl, C2-6-alkenyl and C3-10-cycloalkyl, each of which is optionally substituted with one or more substituents independently selected from hy- droxy, sulfanyl, oxo, halogen, amino, cyano and nitro; and R2 is selected from Cl-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl andC3-10- cycloalkyl, each of which is optionally substituted with one or more substituents independ- ently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6- alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3 10-cycloalkyl, wherein each of hydroxy, sul- fanyl, sulfo, amino, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10- cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1 6-alkyl, C2 6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, Cl-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl andC3-lo-cycloalkyl is op- tionally substituted with one or more substituents independently selected from hydroxy, sul- fanyl, sulfo, oxo, halogen, amino, cyano, nitro, Ct 6-alkyl, C2-alkenyl, aryl, heteroaryl, C34- heterocyclyl and C3 10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl,

C2-6-alkenyl, aryl, heteroaryl, C3$-heterocyclyl and C3 10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and Cs- 10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1 6-alkyl, C2 6-alkenyl, aryl, heteroaryl, C3 8-heterocyclyl and C3 10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, perhalomethyl and perhalomethoxy ; and wherein R2 is optionally covalently bound to R'by an ether, thioether, C-C or C-N bond, to form a ring system with the N-atom to which R'and R2 are bound; and X is O or S; and L is a group such that-C (=X) -L is a hydrolysable group; or a pharmaceutical acceptable salt thereof, or a pharmaceutically acceptable solvate thereof, or any tautomeric forms, stereoisomers, mixture of stereoisomers including a racemic mix- ture, or polymorphs for inhibition of the lipolytic activity of hormone-sensitive lipase against triacylglycerols, dia- cylglycerols, cholesterol acyl esters or steroid acyl esters.

Another aspect of the invention relates to use of a compound of the general formula I wherein R'is selected from hydrogen, C1-6-alkyl, C2-6-alkenyl and C3-10-cycloalkyl, each of which is optionally substituted with one or more substituents independently selected from hy- droxy, sulfanyl, oxo, halogen, amino, cyano and nitro; and R2 is selected from C1 6-alkyl, C2 6-alkenyl, aryl, heteroaryl, C3 8-heterocyclyl and C3 10- cycloalkyl, each of which is optionally substituted with one or more substituents independ- ently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-

alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3 10-cycloalkyl, wherein each of hydroxy, sul- fanyl, sulfo, amino, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3 10- cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1 8-alkyl, C26-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3 10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl is op- tionally substituted with one or more substituents independently selected from hydroxy, sul- fanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3$-heterocyclyl and C3 10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1 6-alkyl, C26-alkenyl, aryl, heteroaryl, C3 8-heterocyclyl and Cs- -cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1 6-alkyl, C2 6-alkenyl, aryl, heteroaryl, C3 8-heterocyclyl and C3 10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, Cl-6-alkyl, C2-6-alkenyl, perhalomethyl and perhalomethoxy ; and wherein R2 is optionally covalently bound to R'by an ether, thioether, C-C or C-N bond, to form a ring system with the N-atom to which R'and R2 are bound; and X is O or S; and L is a group such that-C (=X) -L is a hydrolysable group; or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof, or any tautomeric forms, stereoisomers, mixture of stereoisomers including a racemic mix- ture, or polymorphs for the preparation of a medicament for the treatment of any disorder where it is desirable to modulate the plasma level of free fatty acids, glycerol, LDL-cholesterol, HDL-cholesterol, in- sulin and/or glucose ; and/or

modulate intracellular triacylglycerol and cholesterol ester stores, intracellular level of fatty acids, fatty acid esters such as diacylglycerols, phosphatidic acids, long chain acyl-CoA's as well as citrate or malonyl-CoA ; and/or increase insulin sensitivity in adipose tissue, skeletal muscle, liver or pancreatic ß cells ; and/or modulate insulin secretion from pancreatic p cells.

Another aspect of the invention is the use of a compound of the general formula I for the preparation of a pharmaceutical medicament.

In one embodiment the present invention relates to the use of a compound of the general formula (I) for the preparation of a medicament for the treatment of insulin resistance, diabe- tes type 1, diabetes type 2, metabolic syndrome X, impaired glucose tolerance, hyperglyce- mia, dyslipidemia, obesity, abnormalities of lipoprotein metabolism and any combination thereof.

Another aspect of the invention is pharmaceutical compositions comprising a compound of formula I wherein R'is selected from hydrogen, C1 6-alkyl, C2 6-alkenyl and C3 10-cycloalkyl, each of which is optionally substituted with one or more substituents independently selected from hy- droxy, sulfanyl, oxo, halogen, amino, cyano and nitro; and R2 is selected from C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10- cycloalkyl, each of which is optionally substituted with one or more substituents independ- ently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1 6-alkyl, C26- alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3 10-cycloalkyl, wherein each of hydroxy, sul- fanyl, sulfo, amino, C1 6-alkyl, C24-alkenyl, aryl, heteroaryl, C3 8-heterocyclyl and C3 10- cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1 6-alkyl, C26-alkenyl, aryl,

heteroaryl, C3. 8-heterocyclyl and C3 10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, CI-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl andC3-10-cycloalkyl is op- tionally substituted with one or more substituents independently selected from hydroxy, sul- fanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3 8- heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C24-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3- 10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3$-heterocyclyl and C3 10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, perhalomethyl and perhalomethoxy ; and wherein R2 is optionally covalently bound to R'by an ether, thioether, C-C or C-N bond, to form a ring system with the N-atom to which R'and R2 are bound; and X is O or S ; and L is a group such that-C (=X) -L is a hydrolysable group; or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate thereof, or any tautomeric forms, stereoisomers, mixture of stereoisomers including a racemic mix- ture, or polymorphs.

In another embodiment, the invention is concerned with pharmaceutical compositions con- taining a compound of formula (I) and uses of the compounds of formula (I), wherein X is 0.

In another embodiment, the invention is concerned with pharmaceutical compositions com- prising a compound of formula (I) and uses of the compounds of formula (I), wherein X is 0.

In another embodiment, the invention is concerned with pharmaceutical compositions con- taining a compound of formula (I) and uses of the compounds of formula (I), wherein the group L contains an 0, via which L is bound to the C in formula (I).

In another embodiment, the invention is concerned with pharmaceutical compositions com- prising a compound of formula (I) and uses of the compounds of formula (I), wherein the group L contains an 0, via which L is bound to the C in formula (I).

In another embodiment, the invention is concerned with pharmaceutical compositions con- taining a compound of formula (I) and uses of the compounds of formula (I), wherein the group L contains a N, via which L is bound to the C in formula (I).

In another embodiment, the invention is concerned with pharmaceutical compositions com- prising a compound of formula (I) and uses of the compounds of formula (I), wherein the group L contains a N, via which L is bound to the C in formula (I).

In another embodiment, the invention is concerned with pharmaceutical compositions con- taining a compound of formula (I) and uses of the compounds of formula (I), wherein the group L is selected from the group consisting of

wherein Y is O or S; and Ra1, Ra2, Ra3, Ra4, Ra5 and Ra6 are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C14-alkyl, C2-6-alkenyl, aryl, heteroaryl, C34-heterocyclyl, or C3 10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3 10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl,

wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl and C3 10-cycloalkyl is optionally substituted with one or more substituents inde- pendently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-lo- cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3 10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3$-heterocyclyl and C3 10-cycloalkyl is op- tionally substituted with one or more substituents independently selected from hydroxy, sul- fanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, perhalomethyl and perhalomethoxy.

In another embodiment, the invention is concerned with pharmaceutical compositions con- taining a compound of formula (I) and uses of the compounds of formula (I), wherein at least one of Ra1, Ra2, Ra3, Ra4 Ra5 and Ra6 is F.

In another embodiment, the invention is concerned with pharmaceutical compositions con- taining a compound of formula (I) and uses of the compounds of formula (I), wherein the group L is an optionally substituted-O-phenyl, via which L is bound to the C in formula (I).

In another embodiment, the invention is concerned with pharmaceutical compositions con- taining a compound of formula (I) and uses of the compounds of formula (I), wherein R'and R2 are covalently bound to each other so that the group R'-N-R2 forms a piperazine, said piperazine being bound to the C in formula (I).

In another embodiment, the invention is concerned with pharmaceutical compositions con- taining a compound of formula (I) and uses of the compounds of formula (I), wherein R'and R2 are covalently bound to each other so that the group R'-N-R2forms a piperidine, said piperidine being bound to the C in fornula (I).

In another embodiment, the invention is concerned with pharmaceutical compositions con- taining a compound of formula (I) and uses of the compounds of formula (I), wherein R1 is selected from the group consisting of C1-6-alkyl, C2-6-alkenyl and C3 10-cycloalkyl, each of which is optionally substituted with one or more substituents independently selected from hy- droxy, sulfanyl, oxo, halogen, amino, cyano and nitro.

In another embodiment, the invention is concerned with pharmaceutical compositions con- taining a compound of formula (I) and uses of the compounds of formula (I), wherein R, is methyl.

In yet another embodiment, the invention is concerned with pharmaceutical compositions containing a compound of formula (I) and uses of the compounds of formula (I), wherein R1 is phenyl.

In another embodiment, the invention is concerned with pharmaceutical compositions con- taining a compound of formula (I) and uses of the compounds of formula (I), wherein R2 is a heteroaryl.

In another embodiment, the invention is concerned with pharmaceutical compositions con- taining a compound of formula (I) and uses of the compounds of formula (I), wherein R'is methyl and R2 is phenyl.

In another embodiment, the invention is concerned with pharmaceutical compositions con- taining a compound of formula (I) and uses of the compounds of formula (I), wherein the group L is an optionally substituted-O-phenyl via which L is bound to the C in formula (I), and R'and R2 are covalently bound to each other so that the group R'-N-R2 forms a piperazine, said piperazine being bound to the C in fornula (I).

In another embodiment, the invention is concerned with pharmaceutical compositions con- taining a compound of formula (I) and uses of the compounds of formula (I), wherein the group L is an optionally substituted-O-phenyl via which L is bound to the C in formula (1), and R1 and R2 are covalently bound to each other so that the group R'-N-R2 forms a piperidine, said piperidine being bound to the C in fornula (I).

In another embodiment, the invention is concerned with pharmaceutical compositions con- taining a compound of formula (I) and uses of the compounds of formula (I), wherein the group L is an optionally substituted-O-phenyl via which L is bound to the C in formula (I), and R'is methyl and R2 is phenyl.

In another embodiment, the invention is concerned with pharmaceutical compositions con- taining a compound of formula (I) and uses of the compounds of formula (I), wherein pKa of the group L is between 4 and 12, between 6 and 12, between 7 and 12, between 8 and 12, preferably between 8.5 to 11.5, and most preferable between 9.0 to 11.0.

In another embodiment, the invention is concerned with pharmaceutical compositions con- taining the compounds of formula (I) and uses of the compounds of formula (I), wherein ad- ministration of said compound is by oral administration

In another embodiment, the invention is concerned with pharmaceutical compositions con- taining the compounds of formula (I) and uses of the compounds of formula (I), the nasal, transdermal, pulmonal, or parenteral route.

Another aspect of the invention is a method of treating any disorder where it is desirable to inhibit the lipolytic activity of hormone-sensitive lipase against triacylglycerols, diacylglyc- erols, cholesterol acyl esters or steroid acyl esters, wherein said method comprises the use as described above.

In another embodiment, the invention is concerned with a method of treating any disorder where it is desirable to modulate the plasma level of free fatty acids or to modulate the han- dling, storage and oxidation of intracellular fatty acid and cholesterol, wherein said method comprises the use as described above.

In another embodiment, the invention is concerned with said method, wherein said disorder is selected from the group consisting of insulin resistance, diabetes type 1, diabetes type 2, metabolic syndrome X, impaired glucose tolerance, hyperglycemia, dyslipidemia, obesity, abnormalities of lipoprotein metabolism and any combination thereof.

The present invention also relates to compounds of the general formula 11 wherein R'is selected from Cl-6-alkyl, C2-6-alkenyl and C3 10-cycloalkyl, each of which is op- tionally substituted with one or more substituents independently selected from hydroxy, sul- fanyl, oxo, halogen, amino, cyano and nitro; and R2 is selected from C1^-alkyl, C2 6-alkenyl, aryl, heteroaryl, C3 8-heterocyclyl and C3 10- cycloalkyl, each of which is optionally substituted with one or more substituents independ- ently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6- alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sul- fanyl, sulfo, amino, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3 10- cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3$-heterocyclyl and C3-10-CYCloalkyl, wherein each of hydroxy, sulfanyl, sulfo,

amino, C-alkyl, C2 6-alkenyl, aryl, heteroaryl, C3 8-heterocyclyl and C3 10-cycloalkyl is op- tionally substituted with one or more substituents independently selected from hydroxy, sul- fanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1 6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3$-heterocyclyl and C3 10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3- -cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1 6-alkyl, C2 6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3 10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, perhalomethyl and perhalomethoxy ; and wherein R2 is optionally covalently bound to R'by an ether, thioether, C-C or C-N bond, to form a ring system with the N-atom to which R'and R2are bound; and R3 is selected from hydroxy, sulfanyl, sulfo, amino, C1 6-alkyl, C2 6-alkenyl, aryl, heteroaryl, C3 8-heterocyclyl and C3-10-cycloalkyl, each of which is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1 6-alkyl, C2 6-alkenyl, aryl, heteroaryl, C3 8- heterocyclyl and C3-10-cycloalkyl is optionally substituted with one or more substituents inde- pendently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3$-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10- cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl andC3-10-CYCloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl is op- tionally substituted with one or more substituents independently selected from hydroxy, sul- fanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1 6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl andC3-lo-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, perhalomethyl and perhalomethoxy ; and

X is O or S; or a pharmaceutically acceptable salt thereof, or a pharmaceutical acceptable solvate thereof, or any tautomeric forms, stereoisomers, mixture of stereoisomers including a racemic mix- ture, or polymorphs.

In an aspect of the invention, compounds are of the general formula III wherein R1a and R2a are independently selected from C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3 10-cycloalkyl, each of which is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl C3-6- heterocyclyl and C3 10-cycloalkyl is optionally substituted with one or more substituents inde- pendently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano and nitro, Ci-e- alkyl, C24-alkenyl, aryl, heteroaryl, C3 8-heterocyclyl and C3-10-cycloalkyl, wherein each of hy- droxy, sulfanyl, sulfo, amino, C14-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3- 10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, perhalomethyl and perha- methoxy ; and wherein Ruz is optionally covalently bound to R2a by an ether, thioether, C-C or C-N bond, to form a ring system with the N-atom to which R1a and R2a are bound; and Raa, R5a, R6a and R7a are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3- 10-cycloalkyl, each of which is optionally substituted by one or more substituents selected from hydroxy, sulfanyl, sulfo, oxo, amino, cyano, nitro, Cl-6-alkyl, C2-6-alkenyl, aryl, heteroaryl,

C3 8-heterocyclyl and C3 10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6- alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl is optionally substi- tuted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, perhalomethyl and perhalomethoxy ; and A1a is N or C-R8a ; A2a is N or C-R9a ; A3a is N or C-R10a; A4a is N or C-R11a ; and A5a is N or C- R12a ; and wherein Roba, R9a, R10a, R11a and R12a are independently selected from hydrogen, hydroxy, sul- fanyl, sulfo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3 8- heterocyclyl and C3 10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, Cl-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3$-heterocyclyl and C3 10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3- 10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3 10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, Cl-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3 10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl and C3 10-cycloalkyl is optionally substituted with one or more substituents inde- pendently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, perha- lomethyl and perhalomethoxy.

In one embodiment, the invention is concerned with compounds of formula (III), wherein R2a is phenyl, optionally substituted by halogen or methyl.

In another embodiment, the invention in concerned with compounds of formula (III), wherein Rla is selected from methyl and ethyl, optionally substituted by one or more halogen.

In another embodiment, the invention in concerned with compounds of formula (III), wherein R1a and R2a are covalently bound so as to form a ring system with the N-atom to which they are bound, wherein said ring system is a piperidine, piperazine, morpholine, or thiomor- pholine.

In another embodiment, the invention in concerned with compounds of formula (III), wherein R4a, R5a, R6a and R7a are independently selected from hydrogen, F, CI, C1-6-alkyl, C1-6-alkoxy,

-C(=O) NH2, -NHC (=O)-OH,-S (=0) 2-NH2,-NH-S (=0) 2-OH, hydroxy, amino and perha-<BR> <BR> <BR> <BR> <BR> lomethyl.

In another embodiment, the invention in concerned with compounds of formula (III), wherein A1a,A2a,A3a,A4a and A5a are independently selected from N, CH, CF, C-CI and C-CF3.

In an aspect of the invention, compounds are of the general formula IV wherein R1b and R2b are independently selected from C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3 8-heterocyclyl and C3 10-cycloalkyl, each of which may optionally be substituted with one or more substituents selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10- cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6- alkenyl, aryl, heteroaryl, C3 8-heterocyclyl, and C3 10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl and C3 10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6- alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may op- tionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, perhalomethyl and perhalomethoxy ; wherein Rlb is optionally covalently bound to R2b by an ether, thioether, C-C or C-N bond, to form a ring system with the N-atom to which Rlb and R2b are bound; R5b and R6b are independently selected from hydrogen, hydroxy, sulfanyl, halogen, amino, cyano, nitro, sulfo, Cl-6-alkyl, C2 6-alkenyl, aryl, heteroaryl, C3 8-heterocyclyl and C3 10- cycloalkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, Cl-6-alkyl, C2-6-alkenyl, aryl, het- eroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl is optionally substituted with one or more sub- stituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro,

sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl and C3 10-cycloalkyl is optionally substituted with one or more substituents inde- pendently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, perhalomethyl and perhalomethoxy ; R4b and Ruz are independently selected from hydrogen, hydroxy, sulfanyl, halogen, amino, cyano, nitro, sulfo, C14-alkyl, aryl, heteroaryl, C3-6-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, aryl, heteroaryl, C3-8-heterocyclyl and C3 10- cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, het- eroaryl, C3-8-heterocyclyl andC3-lo-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, C1-6 alkyl, C2 6-alkenyl, aryl, heteroaryl, C3 8-heterocyclyl and C3 10-cycloalkyl is optionally substi- tuted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, perhalomethyl and perhalomethoxy ; and Alb is N or C-R8b ; A2b is N or C-R9b ; A3b is N or C-R10b; ; A4b is N or C-R'1b ; and A5b is N or C- R12b ; and wherein R3b, R9b, R'Ob, R1lb and R12b are selected from hydrogen, hydroxy, sulfanyl, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10- cycloalkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C2-alkenyl, aryl, het- eroaryl, C3 8-heterocyclyl and C3 10-cycloalkyl is optionally substituted with one or more sub- stituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, C1-6-alkenyl, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl and C3 10-cycloalkyl is optionally substituted with one or more substituents inde- pendently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, C1 6-alkyl, per- halomethyl and perhalomethoxy ; wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R4b R5b R6b R7b R8b R9b R10b R11b and R12b In one embodiment, the invention is concerned with compounds of formula IV, wherein R2b is phenyl, optionally substituted by halogen.

In another embodiment, the invention is concerned with compounds of the general formula IV, wherein Rlb is selected from methyl and ethyl, optionally substituted by one or more halo- gen.

In another embodiment, the invention is concerned with compounds of the general formula IV, wherein Rlb and R2b are covalently bound so as to form a ring system with the N-atom to which they are bound, wherein the ring system is a piperidine, piperazine, morpholine, or thiomorpholine.

In another embodiment, the invention is concerned with compounds of the general formula IV, wherein R4b, R5b, R6b and Rlb are independently selected from hydrogen, F, Cl, C14-alkyl, C1 6-alkoxy,-C (=O) NH2, -NHC (=O)-OH,-S (=0) 2-NH2,-NH-S (=0) 2-OH, hydroxy, amino and perhalomethyl.

In another embodiment, the invention is concerned with compounds of the general formula IV, wherein Alb, A2b, A3b, Job and A5b are independently selected from N, CH and CF.

In an aspect of the invention, compounds are of the general formula V wherein R4C, R5C, R6C, R7c and R8c are independently selected from hydrogen, hydroxy, sul- fanyl, amino, halogen, cyano, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, C1-6-alkyl, C1-6- alkoxy, C2 6-alkenyl, aryl, heteroaryl, C3 8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Cl-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl, and C3 10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6- alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3 10-cycloalkyl may op- tionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl,

heteroaryl, C3-8-heterocyclyl and C3 10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and Cs-io- cycloalkyl may optionally be substituted with one or more substituents independently se- lected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-1o-cycloalkyl, perhalomethyl and perha- methoxy ; and R9C, Ploc, puc R12c and R13C are independently selected from hydrogen, sulfanyl, amino, halogen, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl and C3-10-cycloalkyl, wherein each of sulfanyl, amino, sulfo, C14-alkyl, C1-6- alkoxy, C24-alkenyl, aryl, heteroaryl, C34-heterocyclyl and C3 10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C14-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, Ci. e- alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may op- tionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3 10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10- cycloalkyl may optionally be substituted with one or more substituents independently se- lected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, perhalomethyl and perha- methoxy ; and wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R4C R5c, R6c, Rc and R8c ; and wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of Rgc Rlo', R11c R 12c and R13c ; and at least one of R4c, R5c, R6c, R7c, R8c, R9c, R10c, R11c, R12c and R13c are different from hydrogen.

In one embodiment, the invention is concerned with compounds of formula V, wherein R9c, R10c, R11c, R12c and R13c are selected from H and F.

In another embodiment, the invention is concerned with compounds of the general formula V, wherein R4c, Rc, Ros°, R7C and R8c are independently selected from hydrogen, F, Cl, C1-6-alkyl, C1-6-alkoxy, -C(=O) NH2, -NHC (=O)-OH,-S (=0) 2-NH2,-NH-S (=0) 2-OH, hydroxy, amino and perhalomethyl.

In another embodiment, the invention is concerned with compounds of the general formula V, where there are no covalent bonds between any of the substituents R9c, R10c, R11c, R12c and 13c In another embodiment, the invention is concerned with compounds of the general formula V, where there are no covalent bonds between any of the substituents R4c, R5c, R6c, R7c and Rc.

In an aspect of the invention, compounds are of the general formula vol wherein R4d and R5d are independently selected from hydrogen, hydroxy, sulfanyl, amino, C2 6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3 10-cycloalkyl, wherein each of hydroxy, sulfanyl, amino, C2-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3 10-cycloalkyl may optionally be substituted with one or more sub- stituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3 10- cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6- alkenyl, aryl, heteroaryl, C3 8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, Cl-6-alkoxy, C26-alkenyl, aryl, heteroaryl, C3 8- heterocyclyl and C3 10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6- alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3. -heterocyclyl and C3 10-cycloalkyl may op- tionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C38-heterocyclyl, C3-1o-cycloalkyl, perhalomethyl and perhalomethoxy : and

R6d, R7d R8d, R9d, R10d, R11d, R12d, R13d and R14d are independently selected from hydrogen, hydroxy, sulfanyl, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3 10-cycloalkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and Cs. io- cycloalkyl may optionally be substituted with one or more substituents independently se- lected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, Cz-6-alkenyl, aryl, heteroaryl, C3$-heterocyclyl, and C3 10-cycloalkyl, wherein each of the hy- droxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6- alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C14-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, het- eroaryl, C3-8-heterocyclyl and C3 10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, ni- tro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10- cycloalkyl, perhalomethyl and perhalomethoxy : wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R4d, R5d, Rua, R7d, R8d and R9d ; and wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R', R11d R12d R13d and R.

In one embodiment, the invention is concerned with compounds of the general formula VI, wherein R4d and R5d are H.

In another embodiment, the invention is concerned with compounds of the general formula Vi, wherein R6d, R7d, R8d and R9d are selected from the group consisting of hydrogen, F, Cl, C1-6-alkyl, C1-6-alkoxy, -C(=O)NH2, -NHC(=O)-OH, -S(=O)2-NH2, -NH-S(=O)2-OH, hydroxy, amino and perhalomethyl.

In another embodiment, the invention is concerned with compounds of the general formula Vi, wherein R10d R11d R12d R13d and R are selected from the group consisting of hydrogen, F, Cl, C1-6-alkyl, C1-6-alkoxy, -C(=O)NH2, -NHC(=O)-OH, -S(=O) 2-NH2, -NH-S (=0) 2-OH, hy- droxy, amino and perhalomethyl.

In another embodiment, the invention is concerned with compounds of the general formula VI, wherein there are no covalent bonds between any of the substituents R R R R8d and R9d.

In another embodiment, the invention is concerned with compounds of the general formula VI, wherein there are no covalent bonds between any of the substituents R', R, R12d, R13d and R In an aspect of the invention, compounds are of the general formula Vil wherein R4e is selected from hydrogen, hydroxy, sulfanyl, halogen, amino, cyano, nitro, C24- alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of C24-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may op- tionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3 8-heterocyclyl, and C3 10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10- cycloalkyl may optionally be substituted with one or more substituents independently se- lected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3 10-cycloalkyl, wherein each of the hy- droxy, sulfanyl, amino, sulfo, C14-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl and C3 10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Ci-e- alkyl, Cl-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-lo-cycloalkyl, perha- lomethyl and perhalomethoxy : and R5e is selected from hydrogen, F, cyano, C14-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl andC3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and

C3 10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substi- tuted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, Cl-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6- alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may op- tionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3$-heterocyclyl, C3o-cycloalkyl, perhalomethyl and perhalomethoxy ; wherein R4e and R5e may be covalently bound to each other by a C-O bond.

In one embodiment, the invention is concerned with compounds of the general formula VII, wherein R4e or R5e is selected from the group consisting of wherein R6e, R7e, R3e, R9e and R10e are independently selected from hydrogen, hydroxy, sul- fanyl, sulfo, halogen, amino, cyano, nitro, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, Ci. e- alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may op- tionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, sulfo, Cl-6-alkyl, CI-6-alkoxy, C24-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10- cycloalkyl may optionally be substituted with one or more substituents independently se- lected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6- alkoxy, C24-alkenyl.

In another embodiment, the invention is concerned with compounds of the general formula Vil, wherein R4e or R5e is selected from the group consisting of

wherein R6e, R7e, R8e, R9e and R'Oe are independently selected from hydrogen, hydroxy, sul- fanyl, sulfo, halogen, amino, cyano, nitro, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3. 8-heterocyclyl and C3 10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6- alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3 10-cycloalkyl may op- tionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C24-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, CI-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3 10- cycloalkyl may optionally be substituted with one or more substituents independently se- lected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, sulfo, CI-6-alkyl, Ci-e- alkoxy and C2-6-alkenyl.

In another embodiment, the invention is concerned with compounds of the general formula Vil, wherein at least one of the substituents We, R7e, R8e, Ré and R10e are selected from the group consisting of F and perhalomethyl.

In another embodiment, the invention is concerned with compounds of the general formula VII, wherein R4e and We are connected by a C-O bond to form the compound wherein R11e is selected from hydrogen, hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6- alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3 10-cycloalkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Ci-e-

alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, Cl-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, het- eroaryl, C34-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, ni- tro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3 10- cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C14-alkyl, C1-6-alkoxy, C2-6- alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3 10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl C3-10-cycloalkyl, perhalomethyl and perhalomethoxy ; and R12e is selected from hydrogen, F, Cl, C1-6-alkyl, C1-6-alkoxy, -C(=O) NH2, -NHC (=O)-OH,- S (=0) 2-NH2,-NH-S (=0) 2-OH, hydroxy, amino and perhalomethyl.

In an aspect of the invention, compounds are of the general formula VIII wherein R4f, R5f, Ruf, R7, R9f and R10f are independently selected from hydrogen, hydroxy, sulfanyl, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, het- eroaryl, C3 8-heterocyclyl and C3 10-cycloalkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3 10- cycloalkyl may optionally be substituted with one or more substituents independently se- lected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl, wherein each of the hy- droxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl, and C3 10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Cl-6- alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3 10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, het-

eroaryl, C3$-heterocyclyl, and C3 10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, ni- tro, sulfo, Cl-6-alkyl, Cl-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10- cycloalkyl, perhalomethyl and perhalomethoxy : with the proviso that e and R5f are not both methoxy; and R8f is selected from hydrogen, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl and C3-10-cycloalkyl, wherein each of sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3 8-heterocyclyl and C3 10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3 10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3 10-cycloalkyl may optionally be substi- tuted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl and C3-10-cycloalkyl, perhalomethyl and perhalomethoxy ; wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R4f, R5f, R, e and R ; and wherein there may optionally be a covalent bond between R9f and Roof.

In one embodiment, the invention is concerned with compounds of the general formula VIII, wherein R9f and R'of are covalently bound so as to form a ring system with the C-atom to which they are bound.

In another embodiment, the invention is concerned with compounds of the general formula VIII, wherein said ring system is a cycloalkyl, phenyl, heteroaryl, piperidine, piperazine, mor- pholine, or thiomorpholine.

In another embodiment, the invention is concerned with compounds of the general formula VIII, wherein R4f and R8f are connected by a C-O bond to form the compound

wherein Rllf is selected from hydrogen, hydroxy, sulfanyl, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, het- eroaryl, C3 8-heterocyclyl and C3 10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, ni- tro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10- cycloalkyl, perhalomethyl and perhalomethoxy ; and R'7f is selected from hydrogen, F, Cl, Cl-6-alkyl, C1-6-alkoxy, -C (=O) NH2,-NHC (=O)-OH,- S (=0) 2-NH2, -NH-S (=0) 2-OH, hydroxy, amino and perhalomethyl ; and wherein there may optionally be a covalent bond between R9f and Roof.

In an aspect of the invention, compounds are of the general formula IX wherein R49, R59, R69, R7g, R89, R99, Rlog and R"9 are independently selected from hydrogen, hydroxy, sulfanyl, halogen, amino, cyano, nitro, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, het- eroaryl, C3-8-heterocyclyl and C3 10-cycloalkyl, wherein each of C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3$-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino,

cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3 10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, su) C1-6-alkyl, C1-6-alkoxy, C2 6-alkenyl, aryl, heteroaryl, C3-heterocyclyl, and C3 10-cycloalkyl may optionally be substi- tuted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl and C3 10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, CI-6- alkyl, CI-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3 10-cycloalkyl may op- tionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, perhalomethyl and perhalomethoxy : and R12g is selected from the group consisting of-C (=O)-,-C (=O) NH-,-CH2-,-CH2CH2-,- CHR15g-,-CH2CHR15g-,-CHR15g-CH2-, -NH-, -NR15g-, -NHC(=O)-, -NR15g-C(=O)-, -O-, -S-, - S (=O)-,-S (=0) 2- ; wherein R159 is selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, ni- tro, Cl-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, het- eroaryl, C3 8-heterocyclyl and C3 10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, sulfo, C14-alkyl, C1-6-alkoxy, C2-6-alkenyl, perhalomethyl and perhalomethoxy ; and wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R49, R5g, Rsg, R79 and R15g ; and wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R8g, R99, R109, R11g and R'S9 ; and R13g is selected from hydrogen, hydroxy, sulfanyl, halogen, amino, cyano, nitro, Cl-6-alkyl, Cl- 6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3$-heterocyclyl and C3 10-cycloalkyl, wherein each of C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3 10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Cl-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3 8-heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C

6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, c3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3 8-heterocyclyl and C3-1o-cYcloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3 10- cycloalkyl may optionally be substituted with one or more substituents independently se- lected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cyclaolkyl, perhalomethyl and perha- methoxy : and R149 is selected from hydrogen, hydroxy, sulfanyl, halogen, amino, cyano, nitro, C24-alkyl, C 6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cyclaolkyl, wherein each of C2-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Cl-6-alkyl, Cl-6-alkoxy, C2-6-alkenyl, aryi, heteroaryl, C3. 8-heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C 6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3 8-heterocyclyl and C3 10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10- cycloalkyl may optionally be substituted with one or more substituents independently se- lected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Cl-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3$-heterocyclyl, C3- o-cycloalkyl, perhalomethyl and perha- methoxy : and wherein R139 and R149 may optionally be covalently bound to each other.

In one embodiment, the invention is concerned with compounds of the general formula IX, wherein R139 and R149 are covalently bound so as to form a ring system with the N-atom to which they are bound.

In another embodiment, the invention is concerned with compounds of the general formula IX, wherein said ring system is a piperidine, piperazine, morpholine, or thiomorpholine.

In another embodiment, the invention is concerned with compounds of the general formula IX, wherein there are no covalent bonds between any of the substituents R49, R59, R69, R 79 and R159 In another embodiment, the invention is concerned with compounds of the general formula IX, wherein there are no covalent bonds between any of the substituents R89, R99, R109, Rllg and R15g.

In another embodiment, the invention is concerned with compounds of the general formula IX, wherein R4g,R5g,R7g,R8g,R9g,R10g,R11 are selected from the group consisting of hydrogen, F, Cl, C1-6-alkyl, C1-6-alkoxy, -C(=O) NH2, -NHC (=O)-OH,-S (=0) 2-NH2,-NH-S (=0) 2- OH, hydroxy, amino and perhalomethyl.

In an aspect of the invention, compounds are of the general formula X wherein R4h and R5h are independently selected from cyano, C1-6-alkyl, C2-6-alkenyl, aryl, het- eroaryl, C3-8-heterocyclyl and C3 10-cycloalkyl, wherein each of C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3 8-heterocyclyl and C3 10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3$-heterocyclyl, and C3-10-cycloalkyl may optionally be substi- tuted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, CI-6-alkyl, C1-6-alkoxy, C24-alkenyl, aryl, heteroaryl, C3 8- heterocyclyl and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6- alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3$-heterocyclyl, and C3 10-cycloalkyl may op- tionally be substituted with one or more substituents independently selected from hydroxy,

sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, perhalomethyl and perhalomethoxy : and R6h R7h, R8h, R9h, R10h, R12h, R14h and R15h are independently selected from hydrogen, hy- droxy, sulfanyl, halogen, amino, cyano, nitro, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, het- eroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of C1-6-alkyl, C2-6-alkenyl, ayrl, heteroaryl, C3-8-heterocyclyl and C3-1o-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, CI-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, andC3-10-cycloalkyl may optionally be substi- tuted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl and C3-10-cycloalkyl, perhalomethyl and perhalomethoxy : and R11h and R'3h are independently selected from hydrogen, hydroxy, sulfanyl, halogen, amino, cyano, nitro, perhalomethyl, perhalomethoxy, C24-alkyl, methoxy, C3-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of sulfanyl, amino, C24- alkyl, C3 6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C38-heterocyclyl and C3 10-cycloalkyl may op- tionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alekntyl, aryl, heteroaryl, C3 8-heterocyclyl, and C3. 10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and 3. 10- cycloalkyl may optionally be substituted with one or more substituents independently se- lected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl, perhalomethyl and perha- methoxy : and wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R, R, R, R, Ran R9h; and wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R', R11h, R, R13h R14h and R'.

In one embodiment, the invention is concerned with compounds of the general formula X, wherein R6h,R7h,R8h,R9h,R10h,R12h and R14h are selected from the group consisting of hy- drogen, F, Cl, C1-6-alkyl, C1-6-alkoxy, -C(=O)NH2, -NHC(=O)-OH, -S(=O)2-NH2, -NH-S(=O)2- OH, hydroxy, amino and perhalomethyl.

In another embodiment, the invention is concerned with compounds of the general formula X, wherein there are no covalent bonds between R4h, R5h, R5h, R7h, Ran and R9h.

In another embodiment, the invention is concerned with compounds of the general formula X, wherein there are no covalent bonds between R', R, R, R, R and R.

In another embodiment, the invention is concerned with compounds of the general formula X, wherein R'5h is hydrogen.

In another embodiment, the invention is concerned with compounds of the general formula X, wherein R and R are selected from the group consisting of hydrogen, F, Cl, C24-alkyl, methoxy, C3-alkoxy,-NHC (=O)-OH,-S (=0) 2-NH2, -NH-S (=0) 2-OH, hydroxy, amino and perhalomethyl.

In an aspect of the invention, compounds are of the general formula XI 'is selected from hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C1-6-alkyl, C1-6- alkoxy, C2 6-alkenyl, aryl, heteroaryl, C3-heterocyclyl and C3 10-cycloalkyl, wherein each of C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-heterocyclyl, and C3 10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3 10- cycloalkyl may optionally be substituted with one or more substituents independently se- lected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy,

C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3 10-cycloalkyl, wherein each of the hy- droxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6- alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, perha- lomethyl and perhalomethoxy : and R6i, R7i, R8i, R9i, R10i, R14i and R15i are independently selected from hydrogen, hydroxy, sul- fanyl, sulfo, halogen, amino, cyano, nitro, Cl-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3 8-heterocyclyl and C3 10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6- alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3 10-cycloalkyl may op- tionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heteroaryl, and C3 10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3 10- cycloalkyl may optionally be substituted with one or more substituents independently se- lected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3$-heterocyclyl and C3 o-cycloalkyl, perhalomethyl and perha- methoxy : and R11i and R13i are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C1-alkyl, methoxy, C3-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3 8- heterocyclyl and C3 10-cycloalkyl, wherein each of sulfanyl, sulfo, C1-6-alkyl, C3-6-alkoxy, C2-6- alkenyl, aryl, heteroaryl, C3 s-heterocyclyl and C3 10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, Ci. e- alkyl, Cl-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3$-heterocyclyl, and C3-10-cycloalkyl may op- tionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3 8-heterocyclyl and C3-1o-cycloalkyl, perhalomethyl and perhalomethoxy : and R12i is selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, Ci. e- alkyl, C1-alkoxy, C2-6-alkenyl, aryl, heteroaryl, 3-8-heterocyclyl and C3 10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl,

C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more sub- stituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3 10- cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6- alkenyl, aryl, heteroaryl, Cs-s-heterocydyt, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, F, amino, cyano, nitro, sulfo, CI-6-alkyl, Cl-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, perhalomethyl and perhalomethoxy.

In one embodiment, the invention is concerned with compounds of the general formula XI, wherein R6i, R7i, R8i and R9i are selected from the group consisting of hydrogen, F, Cl, C1-6- <BR> <BR> <BR> alkyl, C1 6-alkoxy,-C (=O) NH2, -NHC (=O)-OH,-S (=0) 2-NH2, -NH-S (=0) 2-OH, hydroxy, amino and perhalomethyl.

In another embodiment, the invention is concerned with compounds of the general formula XI, wherein Rlol, R11i, R12i, R13i and R14i are selected from the group consisting of hydrogen, <BR> <BR> <BR> F, Cl, Chalky), C14-alkoxy,-C (=O) NH2, -NHC (=O)-OH,-S (=0) 2-NH2,-NH-S (=0) 2-OH, hy- droxy, amino and perhalomethyl.

In another embodiment, the invention is concerned with compounds of the general formula XI, wherein R15i is hydrogen.

In another embodiment, the invention is concerned with compounds of the general formula Xi, wherein Rlo', R11i R12i, R13i R14i and R15i are selected from the group consisting of H, F and methyl.

In an aspect of the invention, compounds are of the general formula Xll wherein R4i, R5i, R6', R7i, R8i, Rgj and Rloj are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, het- eroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo,

amino, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10- cycloalkyl may optionally be substituted with one or more substituents independently se- lected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, CI-6-alkyl, Cl-6-alkoxy, C2-6-aleknyl,a ryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cyclaolkyl, wherein each of the hy- droxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl, and Cs-1o-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6- alkyl, Cl-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3$-heterocyclyl and C3 10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, het- eroaryl, C3 8-heterocyclyl, and C3 10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, ni- tro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10- cycloalkyl, perhalomethyl and perhalomethoxy : and wherein there may optionally be a covalent bond between the substituents R6i and R7i ; and wherein there may optionally be a covalent bond between R5j and R8j ; and R11j and R12j are independently selected from cyano, C14-alkyl, C24-alkenyl, aryl, heteroaryl, C3 8-heterocyclyl and C3 10-cycloalkyl, wherein each of C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3 8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more sub- stituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, andC3-10- cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6- alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl and C3-10-cycloalkyl, perhalomethyl and perhalomethoxy ; and with the proviso that R9i and R10j are both hydrogen, there may optionally be a covalent bond connecting R11j and R'2j.

In one embodiment, the invention is concerned with compounds of the general formula XII, wherein R4', R5', R6j and R7j are selected from the group consisting of hydrogen, F, Cl, C14-

alkyl, C1-6-alkoxy, -C(=O)NH2, -NHYC(=O)-OH, -S(=O) 2-NH2, -NH-S (=0) 2-OH, hydroxy, amino and perhalomethyl.

In another embodiment, the invention is concerned with compounds of the general formula XII, wherein at least one of the substituents R4i, R5i, R6j and R7j are different from hydrogen.

In another embodiment, the invention is concerned with compounds of the general formula XII, wherein R8'is covalently bound to R5i.

In an aspect of the invention, compounds are of the general formula XIII wherein R4k is selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, het- eroaryl, C34-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, ni- tro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and 3-10- cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6- alkenyl, aryl, heteroaryl, C3 s-heterocyclyl, and C3 10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Cl-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl and C3 10-cycloalkyl, perhalomethyl and perhalomethoxy : and R5k is selected from hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C1-6-alkyl, C1-6- alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3$-heterocyclyl and C3-10-ccylaolkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C1-6-alkoxy, C24-alkenyl, aryl, heteroaryl, C3 8- heterocyclyl and C3 10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Ci. e- alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3 10-cycloalkyl, wherein

each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, het- eroaryl, C3-8-heterocyclyi, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, ni- tro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-10-heterocyclyl and C3-10- cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6- alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, d-e-aikyi, C1-6-alkoxy, C2 6-alkenyl, aryl, heteroaryl, C3 8- heterocyclyl and C3-10-cycloalkyl, perhalomethyl and perhalomethoxy : with the proviso that when R4k is hydrogen, then R5k is not C (=O) N (Me) 2; and R6k R7k, R8k, R9k, R10k, R11k, R13k and R14k are independently selected from hydrogen, hy- droxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl andC3-lo-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10- cycloalkyl may optionally be substituted with one or more substituents independently se- lected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl, wherein each of the hy- droxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl, and C3 10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Cl-6- alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, perha- lomethyl and perhalomethoxy : and R12k is selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, cyano, nitro, C1-6-alkyl, C1-6- alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3$-heterocyclyl and C3-1o-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-o-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3- 8-heterocyclyl, and C3 10-cycloalkyl may optionally be substituted with one or more substitu- ents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Cl-6-alkyl, Cl-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl andC3-10-cycloalkyl, perhalomethyl and perhalomethoxy : and

wherein there may optionally be a covalent bond between any of the substituents selected from the group consisting of R4k, R5k, R7k and R8k ; and wherein there may optionally be a covalent bond between R5k and any one of the substitu- ents R7k and R3k ; and wherein there may optionally be one or more covalent bonds between R', R11k, R, R and R In one embodiment, the invention is concerned with compounds of the general formula XIII, wherein the substituents R4k and R5k are connected by a covalent bond.

In another embodiment, the invention is concerned with compounds of the general formula XIII, wherein the substituents R5k and R8k are connected by a covalent bond.

In another embodiment, the invention is concerned with compounds of the general formula XIII, wherein the substituents R'Ok and R"k are connected by a covalent bond.

In another embodiment, the invention is concerned with compounds of the general formula XIII, wherein the substituents R12k and R13k are connected by a covalent bond.

In another embodiment, the invention is concerned with compounds of the general formula XIII, wherein R6k, R7k, R3k and R9k are selected from the group consisting of hydrogen, F, Cl, hydroxy, amino, methyl, methoxy, ethoxy and perhalomethyl.

In another embodiment, the invention is concerned with compounds of the general formula Il wherein R10k, R11k, R12k, R13k and R14k are selected from the group consisting of hydro- <BR> <BR> <BR> <BR> gen, F, Cl, Chalky), C1-6-alkoxy, -C (=O) NH2, -NHC (=O)-OH,-S (=0) 2-NH2,-NH-S (=0) 2-OH, hydroxy, amino and perhalomethyl.

In an aspect of the invention, compounds are of the general formula XIV

wherein R1 is C1-6-alkyl, C2-6-alkenyl or C3-10-cycloalkyl, each of which is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano and nitro; and R2 is C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, or C3-10-cycloalkyl, each of which is optionally substituted with one or more substituents independently selected from hy- droxy, sulfanyl, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3- 8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, amino, C14-alkyl, C24- alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3 10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3 10- cycloalkyl, wherein each of hydroxy, sulfanyl, amino, Cl-6-alkyl, C24-alkenyl, aryl, heteroaryl, C3. 8-heterocyclyl and C3 10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, perha- lomethyl and perhalomethoxy ; with the proviso that when R'and R2 are identical they are not methyl or benzyl ; and R2 is optionally covalently bound to R'by an ether, thioether or C-C bond, to form a ring sys- tem with the N-atom to which R'and R2 are bound; and R5l, R6l, R8l, R9l, R10l are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3 10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C14-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C 6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3 10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Cl-6-alkyl, CI-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, Cs-s-heterocydyi and C3-1o-cYcloalkyl, perhalomethyl and perhalomethoxy : and R41 and R71 are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C1-6-alkyl, methoxy, C3-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl and C3-10-cycloalkyl, wherein each of sulfanyl, sulfo, amino, C1-6-alkyl, C3-6-

alkoxy, C2 6-alkenyl, aryl, heteroaryl, C3. 8-heterocyclyl and C3 10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl, and C3 10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6- alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may op- tionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, perhalomethyl and perhalomethoxy : and wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R4', R51, R61, R71, R8', R9', R10l, and R11l.

In one embodiment, the invention is concerned with compounds of the general formula XIV, wherein R'and R2are covalently bound so as to form a ring system with the N-atom to which they are bound.

In another embodiment, the invention is concerned with compounds of the general formula XIV, wherein said ring system is a piperidine, piperazine, morpholine, or thiomorpholine.

In another embodiment, the invention is concerned with compounds of the general formula XIV, wherein there are no covalent bonds between R'and R2.

In another embodiment, the invention is concerned with compounds of the general formula XIV, wherein there are no covalent bonds between R8l and any of the substituents selected from the group consisiting of R9', Rio', R111.

In another embodiment, the invention is concerned with compounds of the general formula XIV, wherein there are no covalent bonds between R8l and any of the substituents selected from the group consisting of R4', R, R'and R.

In another embodiment, the invention is concerned with compounds of the general formula XIV, wherein there are no covalent bonds between any of the substituents R41, 41, R51, P, 1, R R8ß, R"andR.

In another embodiment, the invention is concerned with compounds of the general formula XIV, wherein R4', R5', R6l and R7l are selected from the group consisting of hydrogen, F, Cl, <BR> <BR> <BR> C1-6-alkyl, C1-6-alkoxy, -C(=O) NH2, -NHC (=O)-OH,-S (=0) 2-NH2, -NH-S (=0) 2-OH, hydroxy, amino and perhalomethyl.

In an aspect of the invention, compounds are of the general formula XV

wherein R4m is selected from hydrogen, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl and C3-10-cycloalkyl, wherein each of sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, het- eroaryl, C3$-heterocyclyl and C3 10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, ni- tro, sulfo, C14-alkyl, Cl-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10- cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6- alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C14- alkyl, Cl-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, andC3-10-cycloalkyl may op- tionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl,a ryl, heteroaryl, C3 8-heterocyclyl and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10- cycloalkyl may optionally be substituted with one or more substituents independently se- lected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, Cz-6-alkenyl, aryl, heteroaryl, C3$-heterocyclyl, C3_o-cycloalkyl, perhalomethyl and perha- methoxy : and Rsm R6m R7m R8m, R9m Rlom, RUm R12m R13m, R14m, R15m and R16m are independently se- lected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C1-6-alkyl, C1-6- alkoxy, C24-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl and C3 10-cycloalkyl may optionally be substituted with one or more substituents

independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C14- alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, het- eroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, ni- tro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-10-heterocyclyl and C3-10- cycloalkyl, perhalomethyl and perhalomethoxy : and wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R, R5m, R R7m and R8m; and wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R9m, Rlom, Rllm, R, R, R, R m and R.

In one embodiment, the invention is concerned with compounds of the general formula XV, wherein there are no covalent bonds between any of the substituents selected from the group consisting of R5m, Rrm, R7m and R8m.

In another embodiment, the invention is concerned with compounds of the general formula XV, wherein there are no covalent bonds between any of the substituents R9m, R10m, Rllm, R12m and R13m.

In another embodiment, the invention is concerned with compounds of the general formula XV, wherein there are no covalent bonds between any of the substituents R 14m, R'5-and R16m.

In another embodiment, the invention is concerned with compounds of the general formula XV, wherein R4m is covalently bound to R.

In another embodiment, the invention is concerned with compounds of the general formula XV, wherein R5m, R6m, R7m, R8m, R9m, R10m, R11m, R12m, R13m and R14m are selected from the <BR> <BR> <BR> group consisting of hydrogen, F, Cl, C1-6-alkyl, C1-6-alkoxy, -C(=O) NH2, -NHC (=O)-OH,-<BR> <BR> <BR> <BR> <BR> S (=0) 2-NH2, -NH-S (=0) 2-OH, hydroxy, amino and perhalomethyl.

In another embodiment, the invention is concerned with compounds of the general formula XV, wherein R14m, R15m and R16m are selected from the group consisting of hydrogen, F, Cl, <BR> <BR> <BR> C1-6-alkyl, C1-6-alkoxy, -C(=O) NH2, -NHC (=O)-OH,-S (=0) 2-NH2, -NH-S (=0) 2-OH, hydroxy, amino and perhalomethyl.

In an aspect of the invention, compounds are of the general formula XVI

wherein R4"is selected from hydrogen, sulfo, C2-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl and C3-10-cycloalkyl, wherein each of sulfo, C2-6-alkyl, C2-6-alkenyl, aryl, het- eroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C34-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, Cl-6-alkoxy, C2-alkenyl, aryl, heteroaryl, C3$-heterocyclyl, C3 10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, Cl-6-alkyl, Cl-6-alkoXY, C2-6- alkenyl, aryl, heteroaryl, C1-6-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-hetero- cyclyl, C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, Cl-6-alkyl, C1-6- alkoxy, C2-6-alkenyl, aryl, heteroaryl, C1-6-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl, C3-10-cycloalkyl, perhalomethyl and perhalomethoxy ; and Z is selected from S, S (=O) and S (=0) 2 ; and Rsn pen R7n R8n Rsn pion piin R12n R13nandR14nareindependentlyselectedfromhydrO- gen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C1-6-alkyl, C1-6-alkoxy, C2-6- alkenyl, aryl, heteroaryl, C3 8-heterocyclyl and C3 10-cycloalkyl, wherein each of hydroxy, sul- fanyl, sulfo, amino, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl C3-8-heterocyclyl and

C3 10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6- alkoxy, C2 6-alkenyl, aryl, heteroaryl, C34-heterocyclyl, and C3 10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Ci. e- alkyl, Cl-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3 s-heterocyclyl and C3 10-cycloalkyl, perha- lomethyl and perhalomethoxy : and wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R, R, R6n, R7n and R8n,; and wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R', R', R and R ; and at least one of the substituents R5n, R6n, R7n, R8n, R9n, R10n, R11n, R12n, R13n and R14n are dif- ferent from hydrogen.

In one embodiment, the invention is concerned with compounds of the general formula XVI, wherein there are no covalent bonds between any of the substituents R5n, R6n, R and R.

In another embodiment, the invention is concerned with compounds of the general formula XVI, wherein there are no covalent bonds between any of the substituents R', R11n, R12n.

In another embodiment, the invention is concerned with compounds of the general formula XVI, wherein R14n is not covalently bound to any other substituent selected from the group consisting of R4n, R5n, R6n, R7n, R8n, R10n, R11n, R12n.

In another embodiment, the invention is concerned with compounds of the general formula XVI, wherein R is covalently bound to R In another embodiment, the invention is concerned with compounds of the general formula XVI, wherein R5n, R6n, R7n and R8n are independently selected from the group consisting of <BR> <BR> <BR> hydrogen, F, Cl, C14-alkyl, C1-6-alkoxy, -C(=O) NH2, -NHC (=O)-OH,-S (=0) 2-NH2,-NH-S (=0) 2- OH, hydroxy, amino and perhalomethyl.

In another embodiment, the invention is concerned with compounds of the general formula XVI, wherein R14n is selected from the group consisting of hydrogen, F, Cl, C1-6-alkyl, C1-6- alkoxy,-C (=O) NH2,-NHC (=O)-OH,-S (=0) 2-NH2,-NH-S (=0) 2-OH, hydroxy, amino and per- halomethyl.

In an aspect of the invention, compounds are of the general formula XVII

wherein R2° is selected from sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, each of which may optionally be substituted with one or more substitu- ents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3 8-heterocyclyl, and C3 10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, Ce- ao-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, Cl-6-alkyl, C1-6-alkoxy, C2-6- alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3 10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkeny7l, aryl, heteroaryl, C3-8- heterocyclyl, C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1 6-alkoxy, C24-alkenyl, aryl, heteroaryl, C34-heterocyclyl, and C3 10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyi, C3-10-cycloalkyl, perhalomethyl and perhalomethoxy ; with the proviso that R20 is not methyl ; and Ra 40, R60 and Wo are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl and C3 10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, Cl-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3 10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl,

C3-8-heterocyclyi, and C3 10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1- 6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfa, Cl-6-alkyl, Cl-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-1o-cYcloalkyl, perhalomethyl and perhalomethoxy : and A1° is N or C-R8° ; go is N or C-R9° ; A3° is N or C-R10o ; A40 is N or C-R11° ; and A50 is N or C- R12° ; and wherein R8o, R90, Rio', Rio and R12° are independently selected from hydrogen, hydroxy, sul- fanyl, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, C1 6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3 10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3 10- cycloalkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, het- eroaryl, C3-8-heterocyclyl and C3 10-cycloalkyl is optionally substituted with one or more sub- stituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl and C3 10-cycloalkyl is optionally substituted with one or more substituents inde- pendently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, per- halomethyl and perhalomethoxy ; with the proviso that when A, A2o, A30, A4o and A5o are all CH, and R40 R50 R60 and R7o are all hydrogen, then R2o is not phenyl ; and wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R4o, R, R, R, R, R9° Rloo, Rio and R In one embodiment, the invention is concerned with compounds of the general formula XVII, wherein there are no covalent bonds between any of the substituents R4o, R50, R60 and R7o.

In another embodiment, the invention is concerned with compounds of the general formula XVII, wherein there are no covalent bonds between any of the substituents Alto, A2o, A3o, A40 and A50.

In another embodiment, the invention is concerned with compounds of the general formula XVII, wherein R20 is selected from the group consisting of cycloalkyl, phenyl, piperidine, piperazine, morpholine, thiomorpholine and heteroaryl.

In another embodiment, the invention is concerned with compounds of the general formula XVII, wherein R40, R50, R60 and R70 are independently selected from the group consisting of hydrogen, F, Cl, C1-6-alkyl, C1-6-alkoxy, -C(=O) NH2, -NHC (=O)-OH, -S (=0) 2-NH2,-NH-S (=0) 2- OH, hydroxy, amino and perhalomethyl.

In an aspect of the invention, compounds are of the general formula XVIII wherein R4P is selected from hydrogen, sulfo, C2-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl and C3 10-cycloalkyl, wherein each of sulfo, C2-6-alkyl, C2-6-alkenyl, aryl, het- eroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, F, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C34-heterocyclyl, and C3 10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3- 10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6- alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C14-alkyl, CI-6-alkoxy, C2 6-alkenyl, aryl, heteroaryl, C34- heterocyclyl, C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, Cl-6-alkyl, Cl-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, andC3-lo-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl,

oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3 8-heterocyclyl, C3 10-cycloalkyl, perhalomethyl and perhalomethoxy : and R5p, R6P, R7P and R8P are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, F, amino, cyano, C14-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10- cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, Cl-6-alkyl, C1-6-alkoxy, C2-6- alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl, and C3 10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6- alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3 10-cycloalkyl may op- tionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl,a ryl, heteroaryl, C34-heterocyclyl, C3-10-cycloalkyl, perhalomethyl and perhalomethoxy ; and pep Flop, pup R12p, R13p, R14p, R15p and R16p are independently selected from hydrogen, hy- droxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, Cl-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3 10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C14-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10- cycloalkyl may optionally be substituted with one or more substituents independently se- lected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl, wherein each of the hy- droxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3$- heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Ci-e- alkyl, C14-alkoxy, C24-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, perha- lomethyl and perhalomethoxy : and wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of Rasp, R 6P and R'P ; and wherein there may optionally be a covalent bond between R4P and R5P so as to form a chromen ring system; and

wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R9p, R'OP, R"P, R 12p, R 13p, R14P, R15P and R"P ; and E is selected from the group consisting of-O-,-S-,-S (=O)-,-S (=0) 2-, -NR17p- and -CR17pR18p- ; and wherein R17p and R18P are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C 6-alkyl, Cl-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-1o-cYcloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10- cycloalkyl may optionally be substituted with one or more substituents independently se- lected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, CI-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3_8-heterocyclyl, C3- o-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, Cl-6-aikyl, C1-6-alkoxy, C24-alkenyl, aryl, heteroaryl, Cs-s-heterocydy), and C3-10-cycloalkyl may optionally be substituted with one or more substituents independ- ently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6- alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, perhalomethyl and perhalomethoxy.

In one embodiment, the invention is concerned with compounds of the general formula XVIII, wherein E is selected from the group consisting of -O- and -CR17pR18p-.

In another embodiment, the invention is concerned with compounds of the general formula XVIII, wherein R4P and R5P are connected by a covalent bond so as to form said chromen ring system.

In another embodiment, the invention is concerned with compounds of the general formula XVIII, wherein R4P and R5P are connected by a covalent bond so as to form the chromen ring system

wherein R19P is selected from the group consisting of hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, perhalomethyl and perhalomethoxy.

In another embodiment, the invention is concerned with compounds of the general formula XVIII, wherein R4P is selected from the group consisting of wherein R20p, R21p, R22p, R23p and R24p are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, het- eroaryl, Cs-s-heterocydy) and C3 10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3 10- cycloalkyl may optionally be substituted with one or more substituents independently se- lected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, sulfo, CI-6-alkyl, C1-6- alkoxy, C24-alkenyl, perhalomethyl and perhalomethoxy.

In another embodiment, the invention is concerned with compounds of the general formula XVIII, wherein there are no covalent bonds between any of the substituents R4P, RP, R6P, R7P and RP.

In another embodiment, the invention is concerned with compounds of the general formula XVIII, wherein there are no covalent bonds between any of the substituents R9P, R10p, R11p, , R13p, R14p, R15p and R16p.

In another embodiment, the invention is concerned with compounds of the general formula XVIII, wherein R10P and R"P are connected by a covalent bond.

In another embodiment, the invention is concerned with compounds of the general formula XVIII, wherein R9p, R10p, R11p, R12p, R13p, R14p, R15p and R16p are independently selected from hydrogen, F, Cl, C14-alkyl, C14-alkoxy,-C (=O) NH2, -NHC (=O)-OH,-S (=0) 2-NH2, -NH-S (=0) 2- OH, hydroxy, amino and perhalomethyl.

In another embodiment, the invention is concerned with compounds of the general formula XVIII, wherein R5P, R6p, WP and RP are independently selected from hydrogen, F, Cl, Ci. e- alkyl, C-alkoxy,-C (=O) NH2,-NHC (=O)-OH,-S (=0) 2-NH2, -NH-S (=0) 2-OH, hydroxy, amino and perhalomethyl.

In an aspect of the invention, compounds are of the general formula XIX wherein Wq, Rlq, Rlq, R9q, R10q, R11q, R12q, R13q, R14q, R15q, R16q, R17q,and R18q are independ- ently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, Ci-e- alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3 8-heterocyclyl and C3 10-cycloalkyl may optionally be substituted with one or more sub- stituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3 10- cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6- alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-

heterocyclyl, C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, Cl-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3- 8-heterocyclyl, C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6- alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3 10-cycloalkyl may op- tionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, Cg-s-heterocydyi, C3-10-cycloalkyl, perhalomethyl and perhalomethoxy : and R5q and Ruz are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, F, Br, amino, cyano, nitro, C1-alkyl, Cl-6-alkoxy, C24-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3 10- cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C1-6-alkoxy, C2-6- alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3 10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6- alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3$-heterocyclyl, and C3 10-cycloalkyl may op- tionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3$-heterocyclyl, C3, 0-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3 0- cycloalkyl may optionally be substituted with one or more substituents independently se- lected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, -8-heterocyclyi, C3-lo-cycloalkyl, perhalomethyl and perha- methoxy : and wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R4q, R5q, R6q, R7q and R8q ; and wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R9q, Rloq, R11q, R12q, R13q, R14q, R15q, R16q, R17q and R18q.

In one embodiment, the invention is concerned with compounds of the general formula XIX, wherein R4q and R6q are connected by a covalent bond.

In another embodiment, the invention is concerned with compounds of the general formula XIX, wherein R4q is selected from the group consisting of substituted heteroaryl and substi- tuted C34-heterocyclyl.

In another embodiment, the invention is concerned with compounds of the general formula XIX, wherein R4q is selected from the group consisting of wherein R'9q, R2oq, R21q, R22q and R23q are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, het- eroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10- cycloalkyl may optionally be substituted with one or more substituents independently se- lected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6- alkoxy, C2 6-alkenyl, aryl, heteroaryl, C34-heterocyclyl and C3 10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl and C3 10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, het- eroaryl, C34-heterocyclyl and C3, 0-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, sulfo, Ca4-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3- aO-cycloalkyl, perhalomethyl and perhalomethoxy.

In another embodiment, the invention is concerned with compounds of the general formula XIX, wherein there are no covalent bonds between any of the substituents R4q, RSq, Rsq, R'q and R In another embodiment, the invention is concerned with compounds of the general formula XIX, wherein there are no covalent bonds between any of the substituents R9q, R'°q, R 12q 13q R14q R15q, R16q, R17q and R18q.

In another embodiment, the invention is concerned with compounds of the general formula XIX, wherein R10P and R11p are connected by a covalent bond.

In another embodiment, the invention is concerned with compounds of the general formula XIX, wherein R11p and R13P are connected by a covalent bond.

In another embodiment, the invention is concerned with compounds of the general formula XIX, wherein R9q R10q R11q R12q R13q R14q R15q, R16q, R17q and R18q are independently se- lected from hydrogen, F, Cl, C1-6-alkyl, C1 6-alkoxy,-C (=O) NH2,-NHC (=O)-OH,-S (=0) 2-NH2, -NH-S(=O) 2-OH, hydroxy, amino and perhalomethyl.

In another embodiment, the invention is concerned with compounds of the general formula XIX, wherein R9q, Rloq, R'iq, R R'4q, R15q, R16q, R17q and R18q are all hydrogen or F.

In another embodiment, the invention is concerned with compounds of the general formula XIX, wherein R5q, R6q, R7q and R8q are independently selected from hydrogen, F, Cl, Ci. e- alkyl, C1-6-alkoxy, -C(=O)NH2, -NHC(=O)-OH, -S(=O) 2-NH2, -NH-S (=0) 2-OH, hydroxy, amino and perhalomethyl.

In an aspect of the invention, compounds are of the general formula XX wherein R4r is selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, het- eroaryl, C34-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, ni- tro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10- cycloalkyl, wherein each of the hydroxy, sulfanyl, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, Cs-s-heterocydy), and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-

10-cycloalkyl, perhalomethyl and perhalomethoxy : provided that R4ris not methyl or phenyl ; and R5r R6r, R7r, R8r, R9r, R10r, R11r, R12r, R13r, R14r, R15r, R16r, R17r and R18r are independently se- lected from hydrogen, hydroxy, sulfanyl, sulfo, F, amino, cyano, nitro, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3_8-heterocyclyl and C3 10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C14-alkoxy, C24-alkenyl, aryl, heteroaryl, C34-heterocyclyl and C3 10-cycloalkyl may optionally be substituted with one or more substituents independ- ently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6- alkoxy, C2-6alkehyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3 10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl, and C3 10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Cl-6- alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, perha- lomethyl and perhalomethoxy : and wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R5r, R6r, R7r and R8r ; and wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R, R', R', R, R, R, R', R, R and R'.

In one embodiment, the invention is concerned with compounds of the general formula XX, wherein R4r and R5r are connected by a covalent bond.

In another embodiment, the invention is concerned with compounds of the general formula XX, wherein R4r is selected from the group consisting of substituted heteroaryl and substi- tuted C34-heterocyclyl.

In another embodiment, the invention is concerned with compounds of the general formula XX, wherein R4r is selected from the group consisting of

wherein R'9', R20r, R21r, R22r and R23r are independently selected from hydrogen, hydroxy, sul- fanyl, sulfo, halogen, amino, cyano, nitro, Cl-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3 8-heterocyclyl and C3 10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6- alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may op- tionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, sulfo, Cl-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-hetrocyclyl and C3 10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3 10- cycloalkyl may optionally be substituted with one or more substituents independently se- lected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, sulfo, CI-6-alkyl, C1-6- alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3$-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl and C3 10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, perha- lomethyl and perhalomethoxy.

In another embodiment, the invention is concerned with compounds of the general formula XX, wherein there are no covalent bonds between any of the substituents R, R, R7 and R8r.

In another embodiment, the invention is concerned with compounds of the general formula XX, wherein there are no covalent bonds between any of the substituents R9r, R', R', R R13r, R'4r, R15r and R16r.

In another embodiment, the invention is concerned with compounds of the general formula XX, wherein R'°r and Ruz are connected by a covalent bond.

In another embodiment, the invention is concerned with compounds of the general formula XX, wherein R'Ir and R 3r are connected by a covalent bond.

In another embodiment, the invention is concerned with compounds of the general formula XX, wherein R9r R10r, R11r, R12r, R13r, R14r, R15r, R16r, R17r and R18r are independently selected from hydrogen, F, Cl, C1-6-alkyl, C1-6-alkoxy, -C(=O) NH2, -NHC (=O)-OH,-S (=0) 2-NH2, -NH- S (=0) 2-OH, hydroxy, amino and perhalomethyl.

In another embodiment, the invention is concerned with compounds of the general formula XX, wherein Rlr, R'lr, R'Ir, R12r, R14r, R15r R16r, R17r and R18r are all hydrogen or F.

In another embodiment, the invention is concerned with compounds of the general formula XX, wherein R5r, R6r, R7r and R8r are independently selected from hydrogen, F, Cl, C1-6-alkyl,

C1-6-alkoxy, -C(=O)NH2, -NHC(=O)-OH, -S(=O) 2-NH2, -NH-S (=0) 2-OH, hydroxy, amino and perhalomethyl.

In an aspect of the invention, compounds are of the general formula XXI wherein A'S is N or C-R17s ; ks is N or C-R"s ; A3s is N or C-R19s ; A4s is N or C-R20s ; and A5s is N or C R21s ; and wherein R17s, R18s, R19s, R20s and R2's are independently selected from hydrogen, hydroxy, sulfanyl, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C2 6-alkenyl, aryl, heteroaryl, C34-heterocyclyl and C3 10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3 10- cycloalkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C24-alkenyl, aryl, het- eroaryl, C34-heterocyclyl and C3 10-cycloalkyl is optionally substituted with one or more sub- stituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3 10-cycloalkyl, wherein each of hydroxy, sulfanyl, amino, suflo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl is optionally substituted with one or more substituents independently se- lected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3 8-heterocyclyl and C3 10-cycloalkyl, wherein each of hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3 10-cycloalkyl is option- ally substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, perhalomethyl and perhalomethoxy ; and

R5s, R6s, R7s and R8s are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, F, amino, cyano, nitro, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, Cl-6-alkyl, Cl-6-alkoxy, C2-6- alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Cl-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6- alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may op- tionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Cl-6-alkyl, Cl-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C34-heterocyclyl, C3-10-cycloalkyl, perhalomethyl and perhalomethoxy : and R9s Rlos, R11s, R12s, R13s, R14s, R15s and R16s are independently selected from hydrogen, hy- droxy, sulfanyl, sulfo, F, amino, cyano, nitro, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, het- eroaryl, C34-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3 10- cycloalkyl may optionally be substituted with one or more substituents independently se- lected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Cl-6-alkyl, C1-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3$-heterocyclyl, and C3-10-cycloalkyl, wherein each of the hy- droxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl, and C3, 0-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C, 6- alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, perha- lomethyl and perhalomethoxy : and E is selected from the group consisting of -O-, -S-, -S(=O)-, -S(=O)2-, -NR22s- and -CR22sR23s- ; and wherein R22s and R23s are independently selected from hydrogen, hydroxy, sulfanyl ; sulfo, halogen, amino, cyano, nitro, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C14-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3 10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, Ci-

6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3 10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-o-cycloalkyl, perhalomethyl and perhalomethoxy ; and wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R5s, R6s, R7s and R8s ; and wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R9s, Rlos, R11s, R12s, R13s, R14s, R15s, R16s, R18s. R19s, R20s, R21s, R22s and R23s In one embodiment, the invention is concerned with compounds of the general formula X) (l, wherein E is selected from the group consisting of-O-and-CR22sR23S.

In another embodiment, the invention is concerned with compounds of the general formula XXI, wherein there are no covalent bonds between any of the substituents R5s, R6s, R7s and R8s.

In another embodiment, the invention is concerned with compounds of the general formula XXI, wherein Riss, Riss, R7s and R8s are independently selected from the group consisting of hydrogen, F, Cl, C1-6-alkyl, C1-6-alkoxy, -C(=O)NH2, -NHC(=O)-OH, -S(=O)2-NH2, -NH-S-(=O)2- OH, hydroxy, amino and perhalomethyl.

In another embodiment, the invention is concerned with compounds of the general formula XXI, wherein there is a covalent bond between Rlos and R"s.

In another embodiment, the invention is concerned with compounds of the general formula X) (l, wherein there is a covalent bond between R13s and R229.

In another embodiment, the invention is concerned with compounds of the general formula XXI, wherein R, R'os, R11s, R12s, R13s, R14s, R15s and R16s are all hydrogen or F.

In an aspect of the invention, compounds are of the general formula XXII

wherein E is selected from the group consisting of-O-,-S-,-S (=O)-,-S (=0) 2-,-NR13t-and -CR'8tR'9t- ; and Rats R", Ritz R7t, Rats R9t, R10t, R11t, R12t, R13t, R14t, R15t, R16t, R17t, R18t and R19t are independ- ently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, nitro, C1-6-alkyl, C1-6- alkoxy, C24-alkenyl, aryl, heteroaryl, C3 8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl and C3 10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, suflo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3- 8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substitu- ents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, nitro, suifo, Ci. e- alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3 10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, Cl-6-alkyl, C1-6-alkoxy, C2 6-alkenyl, aryl, het- eroaryl, C3-8-heterocyclyl, and C3-1o-cYcloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, nitro, sulfo, Cl-6-alkyl, Cl-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3 10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, nitro, sulfo, C1-6-alkyl, Cl-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3$-heterocyclyl, C3-1o-cycloalkyl, perhalomethyl and perhalomethoxy ; with the proviso that R4t and R5t are not both methyl; and wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R9t, R10t, R11t, R12t, R13t, R14t, R15t, R16t, R17t, R18t and R19t.

In one embodiment, the invention is concerned with compounds of the general formula XXII, wherein E is selected from the group consisting of -O-, -S-, -S(=O)-, -S(=O)2- and -CR18tR19t-.

In another embodiment, the invention is concerned with compounds of the general formula XXII, wherein R'8t is hydrogen or F.

In another embodiment, the invention is concerned with compounds of the general formula XXII, wherein Rlot, R, R4t and R6t are all hydrogen In another embodiment, the invention is concerned with compounds of the general formula XXII, wherein R6', R7t, R3t and R9t are independently selected from the group consisting of hydrogen, F, Cl, C1-6-alkyl, C1-6-alkoxy, -C(=O) NH2, -NHC (=O)-OH,-S (=0) 2-NH2,-NH-S (=0) 2- OH, hydroxy, amino and perhalomethyl.

In another embodiment, the invention is concerned with compounds of the general formula XXII, wherein there is a covalent bond between R11t and R13t.

In another embodiment, the invention is concerned with compounds of the general formula XXII, wherein there is a covalent bond between R13t and R19t.

In another embodiment, the invention is concerned with compounds of the general formula XXXX, wherein R10t R11t R12t, R13t, R14t, R15t, R'6tand R17t are all hydrogen or F.

In an aspect of the invention, compounds are of the general formula XXIII wherein R5U R, Ru R7u, R8u, R9u, R10u, R11u, R12u, R13u, R14u and R15u are independently se- lected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C4-alkyl, C1-6- alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, Cl-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6- alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3, 0-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, het- eroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more

substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, ni- tro, sulfo, CI-6-alkyl, Cl-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3$-heterocyclyl and C3 10- cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6- alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Cl-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl, C3_1o-cycloalkyl, perhalomethyl and perhalomethoxy : with the proviso that R4u, Wu and R6u are not all hydrogen; and E is selected from the group consisting of -O-, -S-, -S(=O)-, -S(=O)2-, NR16u- and -CR16uR17u-; wherein R16u and R17u are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C1-6-alkyl, Cl-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3Æ- heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3 10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C 6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Cl-6-alkyl, Cl-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3 tO- cycloalkyl may optionally be substituted with one or more substituents independently se- lected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, perhalomethyl and perha- methoxy ; and wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R4u, R5U and R6U ; and wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of Wu, R9u, R10u and R11u ; and

wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R, R, R14u R15u, R16u and R.

In one embodiment, the invention is concerned with compounds of the general formula XXIII, wherein E is selected from the group consisting of-O-,-S-,-S (=O)-,-S (=0) 2-and-CR16UR17u- . In another embodiment, the invention is concerned with compounds of the general formula XXIII, wherein R17U is hydrogen or F.

In another embodiment, the invention is concerned with compounds of the general formula XXIII, wherein htere are no covalent bonds between any of the substituents R8u, R9u, R10u and R11u.

In another embodiment, the invention is concerned with compounds of the general formula XXIII, wherein R8U, R9U, Rlou and R11U are independently selected from the group consisting of hydrogen, F, Cl, C1-6-alkyl, C1-6-alkoxy, -C(=O) NH2, -NHC (=O)-OH,-S (=0) 2-NH2, -NH-S (=0) 2- OH, hydroxy, amino and perhalomethyl.

In another embodiment, the invention is concerned with compounds of the general formula XXIII, wherein there is a covalent bond between R u and R In another embodiment, the invention is concerned with compounds of the general formula XXIII, wherein R12u, R13u, R14u and R15u are all selected from the group consisting of hydro- gen, F, methyl and C1-6-alkyl.

In an aspect of the invention, compounds are of the general formula XXIVa-b wherein R4v, R5v, R6v, R7v, R8v, R9v, R10v, R11v, R12v, R13v, R14v, R15v, R16v, R17v and R18v are in- dependently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro,

C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, het- eroaryl, C3-8-heterocyclyl andC3-lo-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, ni- tro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10- cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, CI-6-alkyl, C1-6-alkoxy, C2-6- alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, andC3-lo-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6- alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may op- tionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3$-heterocyclyl, C3-1o-cYcloalkyl, perhalomethyl and perhalomethoxy ; with the proviso that none of the substituents R4V, R'and R 6v are benzothiazolyl or benzooxazolyl ; and E is selected from the group consisting of-O-,-S-,-S (=O)-,-S (=0) 2-,-NR19V-and -CR19vR20v- ; and wherein R19v and R20v are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3- -cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C14-alkyl, C24-alkenyl, aryl, heteroaryl, C3 8-heterocyclyl and C3-1o-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C24-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10- cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, Cl-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3 8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Cl-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3_8-heterocyclyl, C3-1o-cycloalkyl, perhalomethyl and perhalomethoxy ; and wherein there may optionally be a covalent bond between the substituents RUZ and R8V or between the substituents R9v and R10v ; and

wherein there may optionally be a covalent bond between R5V and a substituent selected from R3V and R9V ; and wherein there may be a covalent bond between any of the substituents selected from the group consisting of R4V, R5'and R6v ; and wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of Rl", R, R13v, R14v, R15v, R16v, R17v, R18v, R19v and R20v.

In one embodiment, the invention is concerned with compounds of the general formula XXIV, wherein E is selected from the group consisting of-O-,-S-,-S (=O)-,-S (=0) 2-and-CR19VR20v- In another embodiment, the invention is concerned with compounds of the general formula XXIV, wherein R20v is hydrogen or F.

In another embodiment, the invention is concerned with compounds of the general formula XXIV, wherein there are no covalent bonds between any of the substituents R4v, R5v and R6v.

In another embodiment, the invention is concerned with compounds of the general formula XXIV, wherein there are no covalent bonds between any of the substituents FRv, R8V, Rgv and Rlov.

In another embodiment, the invention is concerned with compounds of the general formula XXIV, wherein there are no covalent bonds between a substituent selected from the group consisting of R4v, R5V and R6v and a substituent selected from the group consisting of R7V, Ra, R9v and R10v.

In another embodiment, the invention is concerned with compounds of the general formula XXIV, wherein R7V, R8v, R9v and R10v are independently selected from the group consisting of hydrogen, F, Cl, C1-6-alkyl, C1-6-alkoxy, -C(=O) NH2, -NHC (=O)-OH,-S (=0) 2-NH2,-NH-S (=0) 2- OH, hydroxy, amino and perhalomethyl.

In another embodiment, the invention is concerned with compounds of the general formula XXIV, wherein there is a covalent bond between R 12v and R".

In another embodiment, the invention is concerned with compounds of the general formula XXIV, wherein R11v, R12v, R13v, R14v, R15v, R16v, R17v and R18v are all hydrogen or F.

In an aspect of the invention, compounds are of the general formula XXV

wherein R4w is selected from hydrogen, hydroxy, amino, sulfo, C2-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3$-heterocyclyl and C3-1o-cycloalkyl, wherein each of hydroxy, amino, sulfo, C24- alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C38- heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, Cl-6- alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may op- tionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C 6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-1o-cycloalkyl, perhalomethyl and perhalomethoxy : with the proviso that R4w is not methyl, morpholine or a 2-chromen derivative; and Z is selected from S, S (=O) and S (=0) 2 ; and FZ5w, R6w Pew RaW, pew plow Rllw, R12w, R13w, R14w, R15w and R16w are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3$-heterocyclyl and C3 10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C14-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3 10-cycloalkyl may optionally be substituted with one or more substituents independ- ently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6- alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl, and C3 10-cycloalkyl may optionally be substituted with one or more substituents

independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C14- alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3 10-cycloalkyl, perha- lomethyl and perhalomethoxy : and E is selected from the group consisting of -O-, -S-, -S(=O)-, -S(=O)2-, -NR17w- and -CR17wR18w-; and wherein R17w and R18w are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C1-6-alkyl, C14-alkoxy, C24-alkenyl, aryl, heteroaryl, C3 8- heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, CI-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, CI-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C 6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, perhalomethyl and perhalomethoxy ; and wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R4W R", R6W R'and R" ; and wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R9W, Rlo', Rllw, R12w, R13w, R14w, R15w, R16w, R17w and R18w.

In one embodiment, the invention is concerned with compounds of the general formula XXV, wherein the only substituents which are covalently bound are R4w and R5w.

In another embodiment, the invention is concerned with compounds of the general formula XXV, wherein there are no covalent bonds between any of the substituents R5W, R6W, R7w and R8w In another embodiment, the invention is concerned with compounds of the general formula XXV, wherein there are no covalent bonds between any of the substituents R9W, R10W, R11W, R R R'5wandR.

In another embodiment, the invention is concerned with compounds of the general formula XXV, wherein E is selected from the group consisting of-O-,-S-,-S (=O)-,-S (=0) 2- and- CR17wR18w-.

In another embodiment, the invention is concerned with compounds of the general formula XXV, wherein R18w is hydrogen or F.

In another embodiment, the invention is concerned with compounds of the general formula XXV, wherein R5w, R6w, R7w and R8w are independently selected from the group consisting of hydrogen, F, Cl, C1 6-alkyl, C1 6-alkoxy,-C (=O) NH2,-NHC (=O)-OH,-S (=0) 2-NH2, -NH-S (=0) 2- OH, hydroxy, amino and perhalomethyl.

In another embodiment, the invention is concerned with compounds of the general formula XXV, wherein there is a covalent bond between R10w and R11w.

In another embodiment, the invention is concerned with compounds of the general formula XXV, wherein there is a covalent bond between R'3wandR.

In another embodiment, the invention is concerned with compounds of the general formula XXV, wherein R9w, R10w, R11w, R12w, R13w, R14w, R15w and R"lw are all hydrogen or F.

In an aspect of the invention, compounds are of the general formula XXVI wherein R4x is selected from imino, C14-alkyl, C24-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3 10-cycloalkyl, wherein each of imino, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl and C3 10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, nitro, sulfo, C1-6-alkyl, C1 6-alkoxy, C2 6-alkenyl, aryl, heteroaryl, C3 8-heterocyclyl, and C3 10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3- 8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substitu- ents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, nitro, sulfo, C14- alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, wherein

each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, het- eroaryl, C3-8-heterocyclyl, and C3-1o-cYcloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, nitro, sulfo, Cl-6-alkyl, Cl-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, het- eroaryl, C3$-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, perhalomethyl and perhalomethoxy ; and R5x, R6x, R7x, R8x, R9x, R10x, R11x, R12x and R13x are independently selected from hydrogen, hy- droxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3 8-heterocyclyl and C3 10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, Cl-6-alkyl, Cl-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl andC3-10- cycloalkyl may optionally be substituted with one or more substituents independently se- lected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl, wherein each of the hy- droxy, sulfanyl, amino, sulfo, Cl-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl, and C3 10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Cl-6- alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, het- eroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, ni- tro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10- cycloalkyl, perhalomethyl and perhalomethoxy ; and E is selected from the group consisting of-O-,-S-,-S (=O)-,-S (=0) 2-,-NR14X-and -CR15xR16x-; wherein R'4xis selected from hydrogen, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl and C3 10-cycloalkyl, wherein each of sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, het- eroaryl, C3-8-heterocyclyl andC3-lo-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, F, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl,

heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, F, amino, cyano, nitro, sulfo, Cl-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, F, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, perhalomethyl and perhalomethoxy ; and R15X and R16X are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C14-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3 10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C14-alkyl, C1-6-alkoxy, C2-6- alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-o-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl, and C3 10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, Ci. e- alkyl, Cl-6-alkoxy, C2. 6-alkenyl, aryl, heteroaryl, C3 8-heterocyclyl, and C3 10-cycloalkyl may op- tionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Cl-6-alkyl, Cl-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, perhalomethyl and perhalomethoxy ; and wherein there may optionally be a covalent bond between the substituents Wx and R5x ; and wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R6x, R7X, R8x and R9x ; and wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of Rlox, Rllx, R12x, R13x, R14x, R15x and R16x.

In one embodiment, the invention is concerned with compounds of the general formula XXVI, wherein R6x, R7x, R8x and R9x are independently selected from the group consisting of hydro- <BR> <BR> <BR> gen, F, Cl, Chalky), C14-alkoxy,-C (=O) NH2, -NHC (=O)-OH,-S (=0) 2-NH2, -NH-S (=0) 2-OH, hydroxy, amino and perhalomethyl.

In another embodiment, the invention is concerned with compounds of the general formula XXVI, wherein Rlox, R11X, R'2x and R 13x are independently selected from the group consisting

of hydrogen, F, Cl, C1-6-alkyl, C1-6-alkoxy, -C(=O) NH2, -NHC (=O)-OH,-S (=0) 2-NH2,-NH- S (=0) 2-OH, hydroxy, amino and perhalomethyl.

In another embodiment, the invention is concerned with compounds of the general formula XXVI, wherein there is a covalent bond between the substituents R x and R In another embodiment, the invention is concerned with compounds of the general formula XXVI, wherein there is a covalent bond between the substituents R10x and R11x.

In another embodiment, the invention is concerned with compounds of the general formula XXVI, wherein there is a covalent bond between Rlox and a substituent selected from R'4x and R'r) x.

In an aspect of the invention, compounds are of the general formula XXVII wherein R4y and R11y are independently selected from imino, C1-6-alkyl, C2-6-alkenyl, aryl, het- eroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of imino, Cl-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl andC3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10- cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, Cl-6-alkyl, Cl-6-alkoXY, C2-6- alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3- -cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6- alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3- 10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-alkoxy, C2-6- alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen,

amino, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, perhalomethyl and perhalomethoxy ; and R5Y, Rosy, R7y, R8Y, R9y and R10Y are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl and C3 10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, CI-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, andC3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C 6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Cl-6-alkyl, CI-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3$-heterocyclyl, C3-1o-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10- cycloalkyl may optionally be substituted with one or more substituents independently se- lected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3$-heterocyclyl, C3_o-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3 10-cycloalkyl may optionally be substituted with one or more substituents independ- ently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6- alkoxy, C24-alkenyl, aryl, heteroaryl, C3$-heterocyclyl, C3-1o-cycloalkyl, perhalomethyl and perhalomethoxy ; and wherein there may optionally be a covalent bond between the substituents R4y and R 5y ; and wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R6y, R'y, R8y and R9y ; and wherein there may optionally be a covalent bond between the substituents Rloy and R11y.

In one embodiment, the invention is concerned with compounds of the general formula XXVII, wherein R6Y, R7Y, R8y and R9y are independently selected from the group consisting of hydrogen, F, Cl, C1-6-alkyl, C1-6-alkoxy, -C(=O)NH2, -NHC(=O)-OH, -S(=O)2-NH2, -NH-S(=O)2- OH, hydroxy, amino and perhalomethyl.

In another embodiment, the invention is concerned with compounds of the general formula XXVII, wherein there are no covalent bonds between any of the substituents R6y, R7y, R8y and R9y.

In another embodiment, the invention is concerned with compounds of the general formula XXVII, wherein there is a covalent bond between the substituents R4y and R5Y.

In another embodiment, the invention is concerned with compounds of the general formula XXVII, wherein there is a covalent bond between the substituents R10y and R11y.

In an aspect of the invention, compounds are of the general formula XXVIII wherein R4z, Razz R9z, Rloz, R11Z R12z R13z, R14z, R15z, R16z and R17z are independently se- lected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C1-6-alkyl, C1-6- alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3. -heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl and C3 10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6- alkyl, CI-6-alkoxy, C2 6-alkenyl, aryl, heteroaryl, C3 8-heterocyclyl, and C3 10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, het- eroaryl, C3 8-heterocyclyl, and C3 10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, ni- tro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10- cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6- alkenyl, aryl, heteroaryl, C3_8-heterocyclyl, and C3 10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Cl-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl, C3-o-cycloalkyl, perhalomethyl and perhalomethoxy ; and

R5Z is a carbon bound substituent selected from C1 6-alkyl, C2 6-alkenyl, aryl, heteroaryl, C3 8- heterocyclyl and C3-10-cycloalkyl, each of which may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, CI-6-alkoxy, C24-alkenyl, aryl, heteroaryl, C3 8-heterocyclyl, and C3 10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3$-heterocyclyl, and C3 10-cycloalkyl may optionally be substi- tuted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl, C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, Cl-6-alkyl, Cl-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyi, andC3-lo-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C34-heterocyclyl, C3 o-cycloalkyl, perhalomethyl and perhalomethoxy ; and R and R'Z are independently selected from hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C1-6-alkyl, C1-6-alkoxy, C26-alkenyl, aryl, heteroaryl, C33-heterocyclyl and C310- cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C1-6-alkoxy, C2-6- alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Cl-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl, and C3 10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6- alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroartyl, C3-8-heterocyclyl, and C3-10-cycloalkyl may op- tionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3$-heterocyclyl, C3 1o-cYcloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10- cycloalkyl may optionally be substituted with one or more substituents independently se- lected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, perhalomethyl and perha- methoxy ; and E is selected from the group consisting of-O-,-S-,-S (=O)-,-S (=0) 2-,-NR18Z-and -CR19zR20z-;

wherein R'8Z is selected from hydrogen, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl and C3-10-cycloalkyl, wherein each of sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, het- eroaryl, C34-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, F, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3 10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, F, amino, cyano, nitro, sulfo, Cl-6-alkyl, CI-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-lo-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3 8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, F, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, perhalomethyl and perhalomethoxy ; and R19Z and R20Z are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C1-6-alkoxy, C2-6- alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3 10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6- alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3 10-cycloalkyl may op- tionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, perhalomethyl and perhalomethoxy ; and wherein there may optionally be a covalent bond between the substituents R4z and R5z ; and wherein there may optionally be a covalent bond between any of the substituents R7Z, R8Z, and R9Z ; and wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of Rloz, R11Z R, R, R, R, R, R, R'8z, R'9z, and R20z.

In one embodiment, the invention is concerned with compounds of the general formula XXVIII, wherein there is a covalent bond between the substituents R'and R5'.

In another embodiment, the invention is concerned with compounds of the general formula XXVIII, wherein R6Z, R7z, R8'and R9'are independently selected from the group consisting of hydrogen, F, Cl, C1-6-alkyl, C1-6-alkoxy, -C (=O) NH2, -NHC (=O)-OH,-S (=0) 2-NH2,-NH-S (=0) 2- OH, hydroxy, amino and perhalomethyl.

In another embodiment, the invention is concerned with compounds of the general formula XXVIII, wherein there is a covalent bond between R13Z and a substituent selected from R13Z and R'9z.

In an aspect of the invention, compounds are of the general formula XXIX wherein R4aa is selected from hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3 10-cycloalkyl, each of which may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl, and C3 10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, Cl-6- alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3 10-cycloalkyl may op- tionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, F, amino, cyano, nitro, sulfo, Cl-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, het- eroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, CI-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10- cycloalkyl may optionally be substituted with one or more substituents independently se- lected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, perhalomethyl and perha- methoxy ; and

R5aa, R6aa, R7aa R8aa, R9aa, R10aa R11aa R12aa and R13aa are independently selected from hy- drogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C1-6-alkyl, C1-6-alkoxy, C2-6- alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sul- fanyl, sulfo, amino, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3- 10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Cl-6-alkyl, Cl. 6- alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, Cl-6-alkyl, Cl-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl, and C3 10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6- alkyl, Cl-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3$-heterocyclyl, C3_,1o-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, het- eroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, ni- tro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10- cycloalkyl, perhalomethyl and perhalomethoxy ; and wherein there may optionally be a covalent bond between the substituents R5aa and R6aa or between the substituent R7aa and R8aa ; and wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R9aa R'oaa, R11aa and ; and E is selected from the group consisting of-O-,-S-,-S (=O)- and -S(=O)2-.

In one embodiment, the invention is concerned with compounds of the general formula XXIX, wherein there is a covalent bond between the substituents R9aa and R10aa.

In another embodiment, the invention is concerned with compounds of the general formula XXIX, wherein R, R, R7aa and R8aa are independently selected from the group consisting of hydrogen, F, Cl, C1-6-alkyl, C1-6-alkoxy, -C(=O) NH2, -NHC (=O)-OH,-S (=0) 2-NH2,-NH- S (=0) 2-OH, hydroxy, amino and perhalomethyl.

In another embodiment, the invention is concerned with compounds of the general formula XXIX, wherein at least one of the substituents R5aa, R6aa, R7aa and R8aa are different from hy- drogen.

In an aspect of the invention, compounds are of the general formula XXX

wherein R4ab is selected from sulfanyl, sulfo, amino, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3 8-heterocyclyl and C3-10-cycloalkyl, each of which may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, CI-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3 10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3$-heterocyclyl, and C3 10-cycloalkyl may optionally be substi- tuted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, F, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl, C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3 10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, perhalomethyl and perhalomethoxy ; and E is selected from the group consisting of-NR13ab-and-CR14abR15ab-; and R5ab, R6ab, R7ab, R8ab, R9ab, R10ab R11ab, R12ab R13ab R14ab and R'5ab are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3$-heterocyclyl and C3 10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independ- ently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6- alkoxy, C24-alkenyl, aryl, heteroaryl, C3-8-heterocyclyi, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, Cl-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1 6-

alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, het- eroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, ni- tro, sulfo, Cl-6-alky Ci. -6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10- cycloalkyl, perhalomethyl and perhalomethoxy ; and wherein there may optionally be a covalent bond between the substituents R5ab and R6ab or between the substituent Rlb and Rlab ; and wherein there may optionally be one or more covalent bonds between any of the substituents selected from the group consisting of R9ab R10ab R11ab R12ab R13ab R14ab and R15ab.

In one embodiment, the invention is concerned with compounds of the general formula XXX, wherein there is a covalent bond between the substituents R9ab and R10ab.

In another embodiment, the invention is concerned with compounds of the general formula XXX, wherein there is a covalent bond between R'O, and a substituent selected from R13ab and R14ab.

In another embodiment, the invention is concerned with compounds of the general formula XXX, wherein R5ab, R6ab, R7ab and R8ab are independently selected from the group consisting of hydrogen, F, Cl, C1-6-alkyl, C1-6-alkoxy, -C(=O)NH2, -NHC(=O)-OH, -S(=O) 2-NH2, -NH- S (=0) 2-OH, hydroxy, amino and perhalomethyl.

In another embodiment, the invention is concerned with compounds of the general formula XXX, wherein at least one of the substituents R5ab, R6ab, R7ab and R, b are different from hy- drogen.

In another embodiment, the invention is concerned with compounds of the general formula XXX, wherein at least one of the substituents R9ab, R'Oab, R11ab, R12ab R13ab R14ab a d R15ab are different from hydrogen.

In an aspect of the invention, compounds are of the general formula XXXI

wherein R4aC is a carbon bound substituent selected from C1-6-alkyl, C2-6-alkenyl, aryl, het- eroaryl, C34-heterocyclyl and C3 10-cycloalkyl, each of which may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1- alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3 10-cycloalkyl may op- tionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, Cs-s-heterocydy), C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10- cycloalkyl may optionally be substituted with one or more substituents independently se- lected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, perhalomethyl and perha- methoxy ; and A lac is N or C-R ; A is N or C-R10ac; and A5ac is N or C-R11ac; and R5ac, R6ac, R7ac, R8ac, R9ac, R10ac and R11ac are independently selected from hydrogen, hy- droxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C34-heterocyclyl and Cs-1o-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C1-6-alkoxy, C24-alkenyl, aryl, heteroaryl, C3 8-heterocyclyl and C3 10- cycloalkyl may optionally be substituted with one or more substituents independently se- lected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3$-heterocyclyl, and C3-10-cycloalkyl, wherein each of the hy- droxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl, and C3 10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Ci. e-

alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, het- eroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, ni- tro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10- cycloalkyl, perhalomethyl and perhalomethoxy ; with the proviso that Anzac is not C- C (OH) (CF3) 2; and A2ac is N or C-R12ac ; and A4ac is N or G R13ac ; wherein R 12ac and R 13ac are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, Cl-6-alkyl, C2-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3 10-cycloalkyl, wherein each of sulfanyl, sulfo, amino, C14-alkyl, C24-alkoxy, C24-alkenyl, aryl, heteroaryl, C34-heterocyclyl and C3 10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3 10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3$-heterocyclyl, and C3 10-cycloalkyl may optionally be substi- tuted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl, C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3 10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, perhalomethyl and perhalomethoxy ; and wherein there may optionally be a covalent bond between R4ac and a substituent selected from the group consisting of R5ac and R6aC ; with the proviso that Flac, A2aC, A3aC, A4ac and A5ac are not all CH; and wherein there may optionally be a covalent bond between any of the substituents R6ac, R7ac and R lac ; and wherein there may optionally be one or more covalent bonds between any of the substituents in A1ac, A2ac, A3ac, A4ac and A5ac

In one embodiment, the invention is concerned with compounds of the general formula XXXI, wherein there is a covalent bond between the substituents R4ac and R6ac.

In another embodiment, the invention is concerned with compounds of the general formula XXXI, wherein there is a covalent bond between A and A4aC.

In another embodiment, the invention is concerned with compounds of the general formula XXXI, wherein there is a covalent bond between A3ac and A2ac.

In another embodiment, the invention is concerned with compounds of the general formula XXXI, wherein R 5a,, R6a,, R7,' and R8aC are independently selected from the group consisting of hydrogen, F, Cl, C1-6-alkyl, C1-6-alkoxy, -C(=O) NH2, -NHC (=O)-OH, -S (=0) 2-NH2, -NH- S (=0) 2-OH, hydroxy, amino and perhalomethyl.

In another embodiment, the invention is concerned with compounds of the general formula XXXI, wherein at least one of the substituents Anzac Anzac Anzac A4ac and Anzac are different from CH.

In an aspect of the invention, compounds are of the general formula XXXIIa-b wherein R4ad is selected from hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C34-heterocyclyl and C3 10-cycloalkyl, each of which may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, Cl-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6- alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3 10-cycloalkyl may op- tionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, F, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, het- eroaryl, C34-heterocyclyl, C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3 10- cycloalkyl may optionally be substituted with one or more substituents independently se-

lected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, perhalomethyl and perha- methoxy ; and R5ad, R6ad, R7ad, R8ad and R9ad are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl and C3 10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C14-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3 10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3 10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C 6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3 10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, Cs-g-heterocydyi, C3 10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, Cl-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3 10- cycloalkyl may optionally be substituted with one or more substituents independently se- lected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3- o-cycloalkyl, perhalomethyl and perha- methoxy ; and pioad g selected from imino, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3 10-cycloalkyl, each of which may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Ch- alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, het- eroaryl, C34-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, ni- tro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10- cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, Cl-6-alkyl, C1-6-alkoxy, C2-6- alkenyl, aryl, heteroaryl, C34-heterocyclyl, and C3 10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C1-6-alkoxy, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl, C3-10-cycloalkyl, perhalomethyl and perhalomethoxy ; and

wherein there may optionally be a covalent bond between R4ad and a substituent selected from R6ad and R7ad ; and wherein there may optionally be a covalent bond between the substituents R9ad and R10ad so as to form a 5-membered ring system.

In one embodiment, the invention is concerned with compounds of the general formula XXXIla-b, wherein the substituents R9ad and R10ad are covalently bound so as to form a 5- membered ring system.

In another embodiment, the invention is concerned with compounds of the general formula XXXIIa-b, wherein said 5-membered ring system comprises at least one nitrogen atom in the ring.

In another embodiment, the invention is concerned with compounds of the general formula XXXIIa-b, wherein said 5-membered ring system contains 5 carbons in the ring.

In another embodiment, the invention is concerned with compounds of the general formula XXXIIa-b, wherein there is a covalent bond between the substituents, and In another embodiment, the invention is concerned with compounds of the general formula XXXIIa-b, wherein R5ad, R6ad, R7ad and R8ad are independently selected from the group con- <BR> <BR> <BR> sisting of hydrogen, F, Cl, C1-6-alkyl, C1 6-alkoxy,-C (=O) NH2, -NHC (=O)-OH,-S (=0) 2-NH2, - NH-S (=0) 2-OH, hydroxy, amino and perhalomethyl.

In another aspect of the invention, compounds are of the general formula XXX))) a-b wherein E is selected from the group consisting of-O-,-S-,-S (=O)-,-S (=0) 2-, -NR16ae- and - CR17aeR18ae-; and

R4ae R5ae D6ae R7ae R8ae, R9ae, R10ae, R11ae, R12ae, R13ae, R14ae, R15ae, R16ae, R17ae and R18ae are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C2-6- alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10- cycloalkyl may optionally be substituted with one or more substituents independently se- lected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl C2-6-alkenyl, aryl, heteroaryl, C34-heterocyclyl, C3 10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hy- droxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, het- eroaryl, C3-8-heterocyclyl and C3 10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3 10-cycloalkyl may op- tionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl, C3-10-cycloalkyl, perhalomethyl and perhalomethoxy ; and wherein there may optionally be a covalent bond between any of the substituents selected from R4ae, R5ae, R6ae and R7ae ; with the proviso that when R5ae and R 6, e are covalently bound they do not form a isoquinolin-3-yl or a substituted isoquinolin-3-yl together with the pyridine which they are both bound to; and wherein there may optionally be a covalent bond between any of the substituents selected from R8ae R9ae R10ae Rl1ae R12ae R13ae R14ae R15ae R16ae, R17ae and R18ae In one embodiment, the invention is concerned with compounds of the general formula XXXIIIa-b, wherein there is a covalent bond between R6ae and R7ae.

In another embodiment, the invention is concerned with compounds of the general formula XXXIIIa-b, wherein there is a covalent bond between R5ae and Rae.

In another embodiment, the invention is concerned with compounds of the general formula XXXlila-b, wherein at least one of R8ae, R9ae R', R11ae, R, R13ae R14ae and R'is se

lected from F, Cl, C1-6-alkyl, C1-6-alkoxy, -C(=O)NH2, -NHC(=O)-OH, -S(=O) 2-NH2, -NH- S (=0) 2-OH, hydroxy, amino and perhalomethyl.

In another aspect of the invention, compounds are of the general formula XXX) V wherein R4af, R5af, R6af, R7af, R8af, R9af, R10af, R11af, R12af, R13af, R14af and R15af are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C1-6-alkyl, C2- 6-alkenyl, aryl, heteroaryl, Cs-s-heterocydyi and C3 10-cycloalkyl, wherein each of hydroxy, sul- fanyl, sulfo, amino, C1-6-alkyl, C2-alkenyl, aryl, heteroaryl, Cm-heterocyclyl and C3 10- cycloalkyl may optionally be substituted with one or more substituents independently se- lected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C34-heterocyclyl, and C3 10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3$-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hy- droxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, het- eroaryl, Cs-s-heterocydyi, C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3 10-cycloalkyl may op- tionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C24-alkenyl, aryl, heteroaryl, C34- heterocyclyl and C3 10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, Ci-e- alkyl, C2-6-alkenyl, aryl, heteroaryl, C3$-heterocyclyl, and C3 10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, perhalomethyl and perhalomethoxy ; and wherein there may optionally be a covalent bond between R6af and any of the substituents selected from R5af and R'af ; and

wherein there may optionally be a covalent bond between the substituents R9af and R10af ; and R16af is selected from hydrogen, hydroxy, sulfanyl, sulfo, amino, CI-6-alkyl, C2-6-alkenyl, C3-8- heterocyclyl and C3 10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C2-6-alkenyl, C3$-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3 10- cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C34-heterocyclyl, and C3-1o-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, Cl-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more sub- stituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, CI-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3$-heterocyclyl and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, Cl-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6- alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, perhalomethyl and per- halomethoxy ; with the proviso that R16af is not methyl ; and wherein there may optionally be a covalent bond between the substituents R12af and R16af.

In one embodiment, the invention is concerned with compounds of the general formula XXXIV, wherein there is a covalent bond between the substituents Waf and R6af.

In another embodiment, the invention is concerned with compounds of the general formula XXXIV, wherein there is a covalent bond between the substituents R9af and R10af.

In another embodiment, the invention is concerned with compounds of the general formula XXX) V, wherein at least one of R8af, R9af, R10af R'laf, R12af. R13af, R14af and R15af is selected from F, Cl, C1-6-alkyl, C1-6-alkoxy, -C(=O)NH2, -NHC(=O)-OH, -S(=O)2-NH2, -NH-S(=O) 2-OH, hydroxy, amino and perhalomethyl.

In another aspect of the invention, compounds are of the general formula XXXV

wherein E is selected from the group consisting of-O-,-S-,-S (=O)-,-S (=0) 2- and- CR16agR17ag ; and R4ag, R5ag, R6ag, R10ag, R11ag, R12ag, R13ag, R16ag and R17ag are independently selected from hy- drogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C34-heterocyclyl and C3 10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, Cl-e-alkyl, C24-alkenyl, aryl, heteroaryl, C34-heterocyclyl and C3-10-cycloalkyl may op- tionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl, and C3 10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6- alkyl, C24-alkenyl, aryl, heteroaryl, C34-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3 10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Cl-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3 10- cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3 10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, perhalomethyl and perhalomethoxy ; with the proviso that R4ag is not-CH2-N (CH3) 2 ; and wherein there may optionally be a covalent bond between the substituents R5ag and R6ag ; and Rlag is selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, cyano, nitro, C1-6-alkyl, C2-6- alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3 10-cycloalkyl, wherein each of hydroxy, sul-

fanyl, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C34- heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, Ci-e- alkyl, C2-6-alkenyl, aryl, heteroaryl, C34-heterocyclyl, and C3 10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, Cs-s-heterocydyi, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and 3-10- cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C34-heterocyclyl, and C3 10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, perhalomethyl and perhalomethoxy ; R3a9, R9ag, R14ag and R15a9 are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C1-6-alkyl, C2--alkenyl, aryl, heteroaryl, C34-heterocyclyl and Cs- 10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C24-alkenyl, aryl, heteroaryl, C3$-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3$-heterocyclyl, and C3 10- cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3$-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more sub- stituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3 10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl, and C3 10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Ci-6-

alkyl, C2-6-alkenyl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, perhalomethyl and perha- methoxy ; and wherein there may optionally be a covalent bond between the substituents R9"and R"'9 ; and wherein there may optionally be a covalent bond between the substituents R'2a9 and R In one embodiment, the invention is concerned with compounds of the general formula XXXV, wherein there is a covalent bond between the substituents R5a9 and R6ag.

In another embodiment, the invention is concerned with compounds of the general formula XXXV, wherein there is a covalent bond between the substituents R9a9 and R'Oag.

In another embodiment, the invention is concerned with compounds of the general formula XXXV, wherein at least one of R8ag, R9ag, R10ag, R11ag, R12ag, R13ag, R14ag and R15ag are se- lected from F, Cl, CI-6-alky C1 6-alkoxy,-C (=O) NH2,-NHC (=O)-OH,-S (=0) 2-NH2,-NH- S (=0) 2-OH, hydroxy, amino and perhalomethyl.

In another aspect of the invention, compounds are of the general formula XXXV) a-b wherein Razz R5ah, R6ah R7ah, R"ah and R9ah are independently selected from hydrogen, hy- droxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3 8-heterocyclyl and C3 10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6- alkyl, C2-6-alkenyl, aryl, heteroaryl, C3$-heterocyclyl and C3 10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3 10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C14-alkyl, C2-6- alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted

with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10- cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3 10- cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C34-heterocyclyl and C3 10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, CI-6-alky C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, perhalomethyl and perhalomethoxy ; with the proviso that R5ah and R6ah are not both CF3 ; and wherein there may optionally be a covalent bond between any of the substituents selected from R4ah, R5ah, R6ah and R7ah ; and wherein there may optionally be a covalent bond between the substituents R and R ; with the proviso that when R and R together with the carbon to which they are bound forms phenyl then R5ah, R6ah, R7ah and R8ah are not all hydrogen.

In one embodiment, the invention is concerned with compounds of the general formula XXXVIa-b, wherein there is a covalent bond between R8ah and R9ah.

In another embodiment, the invention is concerned with compounds of the general formula XXXVIa-b, wherein there is a covalent bond between R6ah and R7ah.

In another embodiment, the invention is concerned with compounds of the general formula XXXVIa-b, wherein there is a covalent bond between R and R' In another embodiment, the invention is concerned with compounds of the general formula XXXVIa-b, wherein at least one of R5ah, Roan, R7ah and R8ah are selected from F, Cl, C14-alkyl, <BR> <BR> <BR> C1-6-alkoxy, -C(=O) NH2, -NHC (=O)-OH,-S (=0) 2-NH2,-NH-S (=0) 2-OH, hydroxy, amino and perhalomethyl.

In another aspect of the invention, compounds are of the general formula XXXVII

R4ai, R5ai, R6ai, R7ai, R8ai and R9ai are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, Cl-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3 10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C24-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and 3-10- cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, Cg-s-heterocydyi, and C3 10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C24-alkenyl, aryl, heteroaryl, Cs-s-heterocydyi, C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more sub- stituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3_8-heterocyclyl and C3 10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl and C3 10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, Ci-6- alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, perhalomethyl and per- halomethoxy ; with the proviso that R4ai is not CH2-N (Me) 2; and wherein there may optionally be a covalent bond between any of the substituents selected from R4ai, R5ai, R6ai and R7a' ; and wherein there may optionally be a covalent bond between the substituents R8a'and R9a' ; with the proviso that R8a'and R9a'together with the carbon to which they are bound do not form 4- methoxy-phenyl, 4-chloro-phenyl or 4-nitro-phenyl.

In one embodiment, the invention is concerned with compounds of the general formula XXXVII, wherein there is a covalent bond between Rlai and R lai.

In another embodiment, the invention is concerned with compounds of the general formula XXXVII, wherein there is a covalent bond between R6ai and R7ai.

In another embodiment, the invention is concerned with compounds of the general formula XXXVII, wherein there is a covalent bond between R5a'and R.

In another embodiment, the invention is concerned with compounds of the general formula XXXVII, wherein at least one of R5ai, Ruai, R7ai and Raa'are selected from F, Cl, C1-6-alkyl, C1-6- alkoxy,-C (=O) NH2,-NHC (=O)-OH,-S (=0) 2-NH2,-NH-S (=0) 2-OH, hydroxy, amino and per- halomethyl.

In another aspect of the invention, compounds are of the general formula XXXVIII wherein R4ai, R5a', R6ai and R'a'are independently selected from amino, cyano, nitro, Ci. e- alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3 1o-cycloalkyl, wherein each of amino, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3 10-cycloalkyl may op- tionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6- alkyl, C24-alkenyl, aryl, heteroaryl, C34-heterocyclyl, and C3 10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C34-heterocyclyl, and C3 10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3 10- cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, Cs-s-heterocydyi and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino,

cyano, nitro, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, perhalomethyl and perhalomethoxy ; and wherein there may optionally be a covalent bond between the substituents R4aj and R5aj ; and wherein there may optionally be a covalent bond between the substituents Rraj and Rai.

In one embodiment, the invention is concerned with compounds of the general formula XXXVIII, wherein there is a covalent bond between R6ai and R7ai.

In another embodiment, the invention is concerned with compounds of the general formula XXXVIII, wherein R6ai, R7ai and said covalent bond are selected so as to form a ring system selected from an optionally substituted piperidine, piperazine, morpholine and thiomor- pholine.

In another embodiment, the invention is concerned with compounds of the general formula XXXVIII, wherein said ring system is selected from piperidine, piperazine, morpholine and thiomorpholine In another embodiment, the invention is concerned with compounds of the general formula XXXVIII, wherein there is a covalent bond between R4aj and R5aj.

In another aspect of the invention, compounds are of the general formula XXXIX wherein R4al, R5ak, R6ak and R7ak are independently selected from amino, cyano, nitro, Cri-6- alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of amino, C14-alkyl, C24-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may op- tionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, Ci-e- alkyl, C2-6-alkenyl, aryl, heteroaryl, C3$-heterocyclyl, and C3 10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo,

halogen, amino, cyano, nitro, sulfo, C14-alkyl, C26-alkenyl, aryl, heteroaryl, C38-heterocyclyl, C3-10-c6ycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, an C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C24-alkenyl, aryl, heteroaryl, C34-heterocyclyl and C3, 0- cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C_6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3$-heterocyclyl, C3-10-cycloalkyl, perhalomethyl and perhalomethoxy ; with the proviso that none of R4akand R5ak are-C (=O)-O- isopropyl ; and wherein there may optionally be a covalent bond between the substituents R4ak and R5ak ; with the proviso that R4ak, R5ak and the nitrogen to which they are bound do not form a substituted tetrazolyl moiety; and wherein there may optionally be a covalent bond between the substituents R6ak and R7ak ; In one embodiment, the invention is concerned with compounds of the general formula XXXIX, wherein there is a covalent bond between Rllak and R7ak.

In another embodiment, the invention is concerned with compounds of the general formula XXXIX, wherein R6ak, R7ak and said covalent bond are selected so as to form a ring system selected from an optionally substituted piperidine, piperazine, morpholine and thiomor- pholine.

In another embodiment, the invention is concerned with compounds of the general formula XXX) X, wherein said ring system is selected from piperidine, piperazine, morpholine and thiomorpholine In another embodiment, the invention is concerned with compounds of the general formula XXXIX, wherein there is a covalent bond between R4ak and R5ak.

In another aspect of the invention, compounds are of the general formula XXXX

wherein R4al and R5al are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and Cs- 10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C34-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3 10- cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, Cs-s-heterocydyi, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, Cl-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, Cs-s-heterocydy), and C3. 10-cycloalkyl may optionally be substituted with one or more sub- stituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3, 0-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl, and C3, 0-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C14- alkyl, C2-6-alkenyl, aryl, C3-10-cycloalkyl, perhalomethyl and perhalomethoxy ; and wherein there may optionally be a covalent bond between R4al and R5a ; with the proviso that R4al and R5al together with the nitrogen to which they are bound do not form 2,5- pyrrolidinedione or an annealed ring system comprising 3 or more rings; and wherein E is selected from the group consisting of-O-,-S-,-S (=O)-,-S (=0) 2- and-NR -CR15alR16al-; and R6al Wal, R8al, R9al Rloal, R11al R12al R13al R14al, R15al and R16al are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl,

aryl, heteroaryl, Cs-s-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C 6-alkyl, C2 6-alkenyi, aryl, heteroaryl, C34-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hy- droxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, CI-6-alkyl, C2-6-alkenyl, aryl, het- eroaryl, C34-heterocyclyl, and C3 10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3 10-cycloalkyl may op- tionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl, C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C14-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3$-heterocyclyl, and C3 10-cycloalkyl may optionally be substi- tuted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C26-alkenyl, aryl, heteroaryl, C34-heterocyclyl and C3 10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C14-alkyl, C2-6- alkenyl, aryl, heteroaryl, Cs-s-heterocydy), and C3 10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and 3-10- cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, perhalomethyl and perhalomethoxy ; and wherein there may optionally be a covalent bond between the substituents R7al and R8al ; and wherein there may optionally be a covalent bond between the substituents R10al and a sub- stituent selected from R 1 and R' In one embodiment, the invention is concerned with compounds of the general formula XXXX, wherein there is a covalent bond between the substituents R4al and R5al.

In another embodiment, the invention is concerned with compounds of the general formula XXXX, wherein there is a covalent bond between the substituents W a'and W a,.

In another embodiment, the invention is concerned with compounds of the general formula XXXX, wherein there is a covalent bond between R10al and a substituent selected from R 14al or R15al

In another embodiment, the invention is concerned with compounds of the general formula XXXX, wherein E is-NR In another embodiment, the invention is concerned with compounds of the general formula XXXX, wherein R14al is selected from F, Cl, C1-6-alkyl, C1-6-alkoxy, -C (=O) NH2, -NHC (=O)-OH, -S(=O)2-NH2, -NH-S(=O)2-OH, hydroxy, amino and perhalomethyl.

In another embodiment, the invention is concerned with compounds of the general formula XXXX, wherein E is -CR15alR16al-.

In another embodiment, the invention is concerned with compounds of the general formula XXXX, wherein R16al is selected from F, Cl, C1-6-alkyl, C1-6-alkoxy, -C(=O) NH2, -NHC (=O)-OH, -S (=0) 2-NH2, -NH-S (=0) 2-OH, hydroxy, amino and perhalomethyl.

In another embodiment, the invention is concerned with compounds of the general formula XXXX, wherein R15al is hydrogen.

In another embodiment, the invention is concerned with compounds of the general formula XXXX, wherein at least one of R6al, Wal, R8al, R9al, R10al R11al R12a'and R13a'are selected from F, Cl, C1-6-alkyl, C1-6-alkoxy, -C(=O) NH2, -NHC (=O)-OH,-S (=0) 2-NH2,-NH-S (=0) 2-OH, hy- droxy, amino and perhalomethyl.

In another aspect of the invention, compounds are of the general formula XXXXI wherein E is selected from the group consisting of-O-,-S-,-S (=O)-,-S (=0) 2- and-NR -CR15amR16am-; and wherein Alam is N or C-R17am; A2am is N or C-R18am; A3am is N or C-R19am; A4am is N or c-R20am. and R6am, R7am, R8am, R9am, R10am, R11am, R12am, R13am, R14am, R15am, R16am, r17am, R18am, R19am and R20am are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, Cl-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl,

wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C14- alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, Cs-g-heterocydyi, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C2-6- alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, wherein each of the hydroxy, sul- fanyl, amino, sulfo, Cl-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, Cs-s-heterocydyi, and C3 10- cycloalkyl may optionally be substituted with one or more substituents independently se- lected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, c2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3, 0-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3 10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hy- droxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, het- eroaryl, C3-8-heterocyclyl and C3 10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may op- tionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl, C3-o-cycloalkyl, perhalomethyl and perhalomethoxy ; with the proviso that R 17am and R20am are not both hydroxy; and wherein there may optionally be a covalent bond between R18am and a substituent selected from R17am and R19am; and wherein there may optionally be a covalent bond between the substituents R'°am and a sub- stituent selected from R'4am and R15am ; and wherein there may optionally be a covalent bond between the substituents R7am and R8am.

In one embodiment, the invention is concerned with compounds of the general formula X I, wherein there is a covalent bond between R18am and a substituents selected from R17am and R19am.

In another embodiment, the invention is concerned with compounds of the general formula XXXXI, wherein there is a covalent bond between R10am and a substituent selected from R14am or R In another embodiment, the invention is concerned with compounds of the general formula XX ? CXI, wherein E is-NR In another embodiment, the invention is concerned with compounds of the general formula XXXXI, wherein R 14am is selected from F, Cl, C1-6-alkyl, C1-6-alkoxy, -C(=O) NH2, -NHC (=O)- OH, -S (=0) 2-NH2, -NH-S (=0) 2-OH, hydroxy, amino and perhalomethyl.

In another embodiment, the invention is concerned with compounds of the general formula XXXXI, wherein E is -CR15amR16am-.

In another embodiment, the invention is concerned with compounds of the general formula XXXXI, wherein R'6am is selected from F, Cl, C1-6-alkyl, C1-6-alkoxy, -C(=O)NH2, -NHC(=O)- OH, -S (=0) 2-NH2, -NH-S (=0) 2-OH, hydroxy, amino and perhalomethyl.

In another embodiment, the invention is concerned with compounds of the general formula XXXXI, wherein R 15am is hydrogen.

In another embodiment, the invention is concerned with compounds of the general formula XXXXI, wherein there is a covalent bond between R'5am and R In another embodiment, the invention is concerned with compounds of the general formula XXXX), wherein at least one of R6am, R7am, R8am, R9am, R10am, R11am, R12am and Rl3am are se- lected from F, Cl, C1-6-alkyl, C1-6-alkoxy, -C(=O) NH2, -NHC (=O)-OH,-S (=0) 2-NH2,-NH- S (=0) 2-OH, hydroxy, amino and perhalomethyl.

In another aspect of the invention, compounds are of the general formula XXXXII wherein E is selected from the group consisting of-O-,-S-,-S (=O)-,-S (=0) 2- and -NR17an-, -CR18anR19an-; and

R4an R5an, R6an, R7an, R8an, R9an, R10an, R11an, R12an, R13an, R14an, R15an, R16an, R17an, R18an and R19an are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, Cr4-alkyl, C24-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C14-alkyl, C2 6-alkenyl, aryl, heteroaryl, C3- heterocyclyl and C3, 0-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6- alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3 10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C2-6- alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, C3-10-cycloalkyl, wherein each of the hydroxy, sul- fanyl, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3 10- cycloalkyl may optionally be substituted with one or more substituents independently se- lected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C24-alkenyl, aryl, heteroaryl, C34-heterocyclyl and C3 10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1 6-alkyl, C2. 6-alkenyl, aryl, heteroaryl, C34-heterocyclyl, and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hy- droxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, het- eroaryl, C34-heterocyclyl and C3 10-cycloalkyl, wherein each of the hydroxy, sulfanyl, amino, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3_,1o-cYcloalkyl may op- tionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, oxo, halogen, amino, cyano, nitro, sulfo, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl, C3-10-cycloalkyl, perhalomethyl and perhalomethoxy ; with the proviso that Wan is not methyl or phenyl ; and wherein there may optionally be a covalent bond between R13an and a substituent selected from R17an and R18an ; and wherein there may optionally be a covalent bond between the substituents R and R In one embodiment, the invention is concerned with compounds of the general formula XXXXII, wherein R4a"is a substituted heteroaryl.

In another embodiment, the invention is concerned with compounds of the general formula XXXXII, wherein said substituted heteroaryl is a substituted pyridine.

In another embodiment, the invention is concerned with compounds of the general formula XXXXII, wherein there is a covalent bond between the substituents W and R.

In another embodiment, the invention is concerned with compounds of the general formula XXXXII, wherein there is a covalent bond between R13an and a substituents selected from 17an 8an In another embodiment, the invention is concerned with compounds of the general formula XXXXII, wherein E is -NR17an-.

In another embodiment, the invention is concerned with compounds of the general formula XXXX)), wherein E is -CR18anR19an-.

In another embodiment, the invention is concerned with compounds of the general formula XXXXII, wherein R'9an is selected from F, Cl, C1-6-alkyl, C1-6-alkoxy, -C(=O) NH2, -NHC (=O)- OH, -S (=0) 2-NH2,-NH-S (=0) 2-OH, hydroxy, amino and perhalomethyl.

In another embodiment, the invention is concerned with compounds of the general formula XXXX (XXXII, wherein R18an is hydrogen.

In another embodiment, the invention is concerned with compounds of the general formula XXXXII, wherein at least one of R5an, R6an, R7an, R8an, R9an, R10an, R11an, R12an, R13an, R14an, Roan and R16an are selected from F, Cl, C1-6-alkyl, C1-6-alkoxy, -C(=O)NH2, -NHC(=O)-OH, - S (=0) 2-NH2,-NH-S (=0) 2-OH, hydroxy, amino and perhalomethyl.

In another aspect of the invention, compounds are of the general formula XXXXIII wherein R4ao is selected from hydrogen, hydroxy, sulfo, halogen, amino, cyano, nitro, Ci. e- alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl, wherein each of hydroxy, sulfo, amino, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3 10- cycloalkyl may optionally be substituted with one or more substituents independently se- lected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C24-alkenyl, aryl, heteroaryl, C34-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, Cl-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3$-heterocyclyl and C3 10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hy-

droxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, aryl, het- eroaryl, C3-8-heterocyclyl and C3 10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may op- tionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl and C3 10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alky, C2-r,-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl andC3-lo-cycloalkyl may optionally be substi- tuted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3- 10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, Cs-s-heterocydy) and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, perhalomethyl and perhalomethoxy ; and wherein R6ao R7ao klao, R8ao, R9ao, R10ao, R11ao and R12ao are independently selected from hy- drogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, Cs-s-heterocydy), and C3-1o-cYcloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3 10-cycloalkyl may op- tionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, Cg. s- heterocyclyl and C3 10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C2 6-alkenyl, aryl, heteroaryl, C34-heterocyclyl and C3 10-cycloalkyl may optionally be substi- tuted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3 -cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, Cl-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C34-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, Ci-e- alkyl, C2-6-alkenyl, aryl, heteroaryl, c3-8-heterocyclyl and C3 10-cycloalkyl, wherein each of hy- droxy, sulfanyl, sulfo, amino, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3- 10-cycloalkyl may optionally be substituted with one or more substituents independently se-

lected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, perhalomethyl and perhalomethoxy ; with the proviso that any one of R6a° and R8a° is not methyl ; and with the further proviso that R4ao, R5aO R6ao R7ao and R8ao are not all hydrogen; and wherein there may optionally be a covalent bond beween R4ao and R6ao ; and wherein there may optionally be a covalent bond between R7ao and R8ao ; and wherein there may optionally be a covalent bond between R9ao and R10ao.

In one embodiment the invention is concerned with compounds of the general formula XXXXIII, wherein R5ao, R6ao, R7ao and R8ao are independently selected from hydrogen and fluor.

In another embodiment the invention is concerned with compounds of the general formula XXXXIII, wherein R9ao, R10ao, R11ao and R10ao are independently selected from hydrogen and fluor.

In another aspect of the invention, compounds are of the general formulae X ? OCXIVa-b wherein R"P and R2aP are independently selected from C1-6-alkyl, C2-6-alkenyl, aryl, het- eroaryl, C34-heterocyclyl, and C3 10-cycloalkyl, wherein each of C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alyl, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl and C3 10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, nitro, Cl-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy,

sulfanyl, sulfo, amino, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3$-heterocyclyl and C3 10- cycloalkyl may optionally be substituted with one or more substituents independently se- lected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, Cs-s-heterocydyi and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hy- droxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C24-alkenyl, aryl, het- eroaryl, C34-heterocyclyl and C3 10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may op- tionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, perhalomethyl and perhalomethoxy ; with the proviso that if R1aP and R2aP are identical then they are not methyl or ethyl ; and wherein there may optionally be a covalent bond between the substituents R1aP and R2aP ; and wherein R5aP, R6aP and R7aP are independently selected from hydrogen and F; and wherein R4aP is selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, ni- tro, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, an C3-10-cycloalkyl wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl and C3 10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6- alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3 10-cycloalkyl, wherein each of hy- droxy, sulfanyl, sulfo, amino, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3- 10-cycloalkyl may optionally be substituted with one or more substituents independently se- lected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, Cl-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C34-heterocyclyl and C3 10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, Cl-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl andC3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hy- droxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, CI-6-alkyl, C2-alkenyl, aryl, het- eroaryl, C3$-heterocyclyl and C3 1o-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C34-heterocyclyl and C3-10-cycloalkyl may op- tionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-

heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1 6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3 10-cycloalkyl may optionally be substi- tuted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1 6-alkyl, C2 6-alkenyl, perhalomethyl and perhalomethoxy ; with the proviso that R4ap is not methyl.

In one embodiment the invention is concerned with compounds of the general formulae XXXXIVa-b, wherein R1aP and R2aP are not identical.

In another aspect of the invention, compounds are of the general formulae XXXXVa-b wherein R"I and R2aq are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3$-heterocyclyl, and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C34-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, aryl, heteeroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, c2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl and C3 10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6- alkyl, C24-alkenyl, aryl, heteroaryl, C34-heterocyclyl and C3 10-cycloalkyl, wherein each of hy- droxy, sulfanyl, sulfo, amino, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-

10-cycloalkyl may optionally be substituted with one or more substituents independently se- lected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C34-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hy- droxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, perha- lomethyl and perhalomethoxy ; with the proviso that R laq and R2aq are not both methyl ; and wherein there may optionally be a covalent bond between R'aq and R2aq ; and wherein R3aq, R4aq, R5aq, R6aq, R7aq, R8aq, R9aq, R10aq, and R11ao are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hy- droxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2--alkenyl, aryl, het- eroaryl, Cs-s-heterocydyi and C3 10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, Cl-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3 10-cycloalkyl may op- tionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl and C3 10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substi- tuted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3- 10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, Cs-s-heterocydyi and C3 10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl and C3 10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, Cl-6- alkyl, C2-6-alkenyl, perhalomethyl and perhalomethoxy ; and wherein there may optionally be a covalent bond between R4aq and R laq ; and

wherein R3, q is selected from the group consisting of-C (=O)-,-C (=O) NH-,-CH2-,-CH2CH2-, <BR> <BR> <BR> -CHF-, -CH2CHF-, -CHFCH2-, -NH-, -S(=O) 2-NH-, -NH-S (=0) 2-, -NHC (=O)-,-O-,-S-,-S (=O)-<BR> <BR> <BR> <BR> <BR> , -S (=0) 2- ; and wherein there may optionally be a covalent bond between two substituents selected from R8aq, R9aq, R10aq and R11ao, In one embodiment the invention is concerned with compounds of the general formulae XXXXVa-b, wherein there is one covalent bond between the substituents R'and R2.

In another embodiment the invention is concerned with compounds of the general formulae XXXXVa-b, wherein R4aq, R5aq, R6aq and RIq are independently selected from hydrogen and fluor.

In another embodiment the invention is concerned with compounds of the general formula XXXXVa-b, wherein R3aq is selected from-O-,-S-,-CH2-,-CH2CH2-,-NH-,-NH-C (=O)-,- C (=O)-NH-,-S (=0) 2-NH- and -NH-S(=O) 2-.

In another aspect of the invention, compounds are of the general formula XXXXVI wherein A1ar is N or C-R10a ; and A2ar is N or C-R11ar; and A3ar is N or C-R12ar ; and wherein R1ar, R2ar, R3ar, R4ar, R5ar, R6ar, R7ar, R8ar, R9ar, R10ar, R'and R are independently selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C1-6-alkyl, C2- 6-alkenyl, aryl, heteroaryl, C34-heterocyclyl, and C3 10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10- cycloalkyl may optionally be substituted with one or more substituents independently se- lected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3 10-cycloalkyl, wherein each of hydroxy, sulfanyl,

sulfo, amino, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hy- droxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1 6-alkyl, C24-alkenyl, aryl, het- eroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, CI-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl andC3-10-cycloalkyl may op- tionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl and C3 10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1 6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substi- tuted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3- 10-cycloalkyl wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, Cs-s-heterocydyi and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, perhalomethyl and perhalomethoxy ; with the proviso that if Rlar and R2ar are identical then they are not methyl or ethyl ; and wherein there may optionally be a covalent bond between R'and R In one embodiment the invention is concerned with compounds of the general formula XXXXVI, wherein R9ar is S (=O) 2-R 13ar or C (=o)-R13ar ; and wherein R'3ar is selected from hy- droxy, sulfanyl, sulfo, amino, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3- 10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, Cs-s-heterocydy) and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, Cl-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl andC3-10-cycloalkyl,. wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, Ci-e- alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hy- droxy, sulfanyl, sulfo, amino, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3- lo-cycloalkyl may optionally be substituted with one or more substituents independently se- lected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, Cr4-alkyl, C24-alkenyl, aryl, heteroaryl, C3$-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-alkyl, C2-6-alkeny, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl

may optionally be substituted with one or more substituents independently selected from hy- droxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, perha- lomethyl and perhalomethoxy In another embodiment the invention is concerned with compounds of the general formula XXXXVI, wherein R1ar and R2ar are not identical.

In another embodiment the invention is concerned with compounds of the general formula XXXXVI, wherein there is a covalent bond between the substituents R1ar and R2ar.

In another aspect of the invention, compounds are of the general formula XXXXVII wherein R'as, R3as Ruas, R4as, R5as, R6as, R7as, R8as and R9as are independetly selected from hydrogen and fluor ; and wherein R10as is selected from aryl and heteroaryl, which is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl and C3 10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, Ci. e- alkyl, C2_s-alkenyl, aryl, heteroaryl, C34-heterocyclyl and C3-10-cycloalkyl, wherein each of hy- droxy, sulfanyl, sulfo, amino, Cl-6-alkyl, C24-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3- 10-cycloalkyl may optionally be substituted with one or more substituents independently se- lected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C34-heterocyclyl and C3 10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hy- droxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, aryl, het- eroaryl, Cs-s-heterocydyi and C3 10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo,

amino, Cl-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl andC3-10-cycloalkyl may op- tionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C24-alkenyl, perhalomethyl and perhalomethoxy ; and wherein R12as is selected from hydrogen, hydroxy, sulfanyl, sulfo, amino, cyano, C1-6-alkyl, C2- 6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10- cycloalkyl may optionally be substituted with one or more substituents independently se- lected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C34-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C2 6-alkenyl, aryl, heteroaryl, C34-heterocyclyl and C3 10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hy- droxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C24-alkenyl, aryl, het- eroaryl, C34-heterocyclyl and C3 10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may op- tionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl and C3, 0-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substi- tuted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3- rO-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3 8-heterocyclyl and C3 10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, Cl-6-alkyl, C24-alkenyl, perhalomethyl and perhalomethoxy ; and wherein R13as, R14as, R15as and R16as are independently selected from hydrogen, hydroxy, sul- fanyl, sulfo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl, and C3 10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, Cl-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substi- tuted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3- 10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, Cs-s-heterocydy) and C3-1o-cYcloalkyl may optionally be substituted with one or

more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C14-alkyl, C24-alkenyl, aryl, heteroaryl, C34- heterocyclyl and C3 10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, Ci-e- alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hy- droxy, sulfanyl, sulfo, amino, C14-alkyl, C2 6-alkenyl, aryl, heteroaryl, C34-heterocyclyl and C3 10-cycloalkyl may optionally be substituted with one or more substituents independently se- lected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1 6-alkyl, C24-alkenyl, aryl, heteroaryl, C34-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, Cl-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl andC3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hy- droxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C14-alkyl, C24-aikenyl, perha- lomethyl and perhalomethoxy ; with the proviso that R12as, R13as, R14as, R15as and R16asare not all hydrogen; and wherein there may optionally be a covalent bond between the substituents R'3aS and R'4as.

In one embodiment the invention is concerned with compounds of the general formula XXXXVII, wherein R13as, R14as, R15as and R16as are indepdnently selected from hydrogen and fluor.

In another aspect of the invention, compounds are of the general formula XXXXVIII wherein R5as, R6at, R7at R8at, R9at, R10at R11at, R12at, R13at R14at, R15at, R16at, R17at and R18at are in- dependently selected from hydrogen and fluor ; and wherein R4at is selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl, and C3 10-cycloalkyl, wherein each

of hydroxy, sulfanyl, sulfo, amino, CI-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3, 0-cycloalkyl may optionally be substituted with one or more substituents independ- ently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6- alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sul- fanyl, sulfo, amino, Cl-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl andC3-10- cycloalkyl may optionally be substituted with one or more substituents independently se- lected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, Cs-s-heterocydy) and C3 10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, Cl-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl andC3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hy- droxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, aryl, het- eroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, Cl-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl andC3-lo-cycloalkyl may op- tionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substi- tuted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C, -alkyl, C2-6-alkenyl, perhalomethyl and perhalomethoxy ; and wherein R'9at is selected from hydrogen, hydroxy, sulfanyl, sulfo, halogen, amino, cyano, Ci.

6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3$-heterocyclyl, and C3-1o-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6- alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sul- fanyl, sulfo, amino, Cl-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl andC3-10- cycloalkyl may optionally be substituted with one or more substituents independently se- lected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may optionally be substituted with one or more substituents independently selected from hy- droxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C24-alkenyl, aryl, het- eroaryl, Cs-s-heterocydy) and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl may op-

tionally be substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, fluor, iodine, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3 8-heterocyclyl and C3-10-cycloalkyl ; with the proviso that R'9at is not methoxy.

In one embodiment the invention is concerned with compounds of the general formula XXXXVII, wherein R5at, R6at, R7at R8at, R9at, R10at R11at, R12at, R13at R14at, R15at, R16at, R17at and R18at are all hydrogen.

In another embodiment the invention is concerned with compounds of the general formula XXXXVIII, wherein R4at is an optionally substituted aryl or heteroaryl.

In another embodiment, the invention is concerned with compounds of the general formulae I-XXXXVIII, wherein said compound comprises only one F.

In another embodiment, the invention is concerned with compounds of the general formulae I-XXXXVIII, wherein said compound comprises two F and preferably three F.

In another embodiment, the invention is concerned with compounds of the general formulae I-XXXXVIII, wherein said compound comprises a CF3 moiety.

In another embodiment, the invention is concerned with compounds of the general formulae I-XXXXVIII, wherein said compound comprises a hydrophilic substituent selected from the group consisting of hydroxy, amino, C1-6-alkoxy, -C(=O)NH2, -NHC(=O)-OH, -S(=O)2-NH2, - NHS (=0) 2-OH,-NHC (=O)-R1am, -NHS(=O)2-R1am, -N(R1am)C(=O)-R2am, -N(R1am)S(=O)2-R2am, wherein R lam and R2am are independently selected from Cl-6-alkyl.

In another embodiment, the invention is concerned with compounds of the general formulae I-XXXXVIII, wherein said compound comprises a moiety selected from the group consisting of Examples of specific compounds of the invention are:

Methyl-phenyl-carbamic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester, Methyl-phenyl-carbamic acid 3- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester, Methyl-phenyl-carbamic acid 4- (3, 5-dichloro-pyridin-2-yloxy)-phenyl ester, Methyl-phenyl-carbamic acid 4- (5-trifluoromethyl-pyridin-2-ylamino)-phenyl ester, Methyl-phenyl-carbamic acid 4- (3, 5-dichloro-pyridin-4-yloxy)-phenyl ester, Methyl-phenyl-carbamic acid 4- (4-trifluoromethyl-phenoxy)-phenyl ester, Methyl-phenyl-carbamic acid 4- (2-cyano-5-trifluoromethyl-pyridine-3-yloxy)-phenyl ester, Methyl-phenyl-carbamic acid 2-benzenesulfonyl-4- (3-chloro-5-trifluoromethyl-pyridine-2- yloxy)-phenyl ester, Methyl-phenyl-carbamic acid 4-tert-butoxy-phenyl ester, Methyl-phenyl-carbamic acid 3- (4-fluorobenzyl)-4-methyl-2-oxo-2H-chromen-7-yi ester, Methyl-phenyl-carbamic acid 4-phenoxy-phenyl ester, Methyl-phenyl-carbamic acid 4- (4-chlorobenzoyl)-phenyl ester, Methyl-phenyl-carbamic acid 4- (3-chloro-5-trifluoromethyl)-pyridine-2-yloxy)-phenyl ester, Methyl-phenyl-carbamic acid 4- [4- (4-chloro-phenyl)-thiazol-2-yl]-phenyl ester, Methyl-phenyl-carbamic acid 4-pyrrol-1-yl-phenyl ester, Methyl-phenyl-carbamic acid 4-imidazol-1-yl-phenyl ester, Methyl-phenyl-carbamic acid 4- (3-chloro-5-trifluoromethyl)-pyridine-2-ylmethyl)-phenyl ester, Methyl-phenyl-carbamic acid 4-trifluoromethylsulfanyl-phenyl ester, Methyl-phenyl-carbamic acid 4-pentafluoroethyloxy-phenyl ester, Methyl-phenyl-carbamic acid 4-benzyloxy-phenyl ester, Methyl-phenyl-carbamic acid 4-benzyl-phenyl ester, Methyl-phenyl-carbamic acid 4'-cyano-biphenyl-4-yl-ester, Methyl-phenyl-carbamic acid 4'-bromo-biphenyl-4-yl-ester, Methyl-phenyl-carbamic acid biphenyl-4-yl-ester, Methyl-phenyl-carbamic acid 4- [3- (4-chlorophenyl)-ureido]-phenyl ester, Methyl-phenyl-carbamic acid 4- (4-nitro-phenoxy)-phenyl ester, Methyl-phenyl-carbamic acid 4-heptylsulfanyl-phenyl ester, Methyl-phenyl-carbamic acid 4-butoxy-phenyl ester, Methyl-phenyl-carbamic acid 4- (4-chloro-benzenesulfonyl)-phenyl ester, Methyl-phenyl-carbamic acid 4- (4-chloromethyl-thiazol-2-yi)-phenyl ester, Methyl-phenyl-carbamic acid 4- (4, 4-dimethyl-2, 6-dioxo-piperidin-1-yl)-phenyl ester, cis-Methyl-phenyl-carbamic acid 4- (1, 3-dioxo-octahydro-isoindol-2-yl)-phenyl ester, Methyl-phenyl-carbamic acid 4- (cyclohexanecarbonyl-amino)-phenyl ester, Methyl-phenyl-carbamic acid 4- (2-cyclohexyl-acetylamino)-phenyl ester,

cis/trans-Methyl-phenyl-carbamic acid 4- [ (4-tert-butyl-cyclohexanecarbonyl)-amino]-phenyl ester, cis-Methyl-phenyl-carbamic acid 4- [ (4-tert-butyl-cyclohexanecarbonyl)-amino]-phenyl ester, trans-Methyl-phenyl-carbamic acid 4- [ (4-tert-butyl-cyclohexanecarbonyl)-amino]-phenyl es- ter, Methyl-phenyl-carbamic acid 4- (3, 3-dimethyl-butyrylamino)-phenyl ester, Methyl-phenyl-carbamic acid 3-benzyl-4-methyl-2-oxo-2H-chromen-7-yl ester, Methyl-phenyl-carbamic acid 3- (3, 4-dichloro-benzyl)-4-methyl-2-oxo-2H-chromen-7-yl ester, <BR> <BR> <BR> Methyl-phenyl-carbamic acid 3-(2-chloro-6-fluoro-benzyl)-4-methyl-2-oxo-2H-chromen-7-yl ester, Methyl-phenyl-carbamic acid 3- (2, 6-dichloro-benzyl)-4-methyl-2-oxo-2H-chromen-7-yl ester, <BR> <BR> <BR> Methyl-phenyl-carbamic acid 3- (2, 6-dichloro-benzyl)-6-chloro-4-methyl-2-oxo-2H-chromen-7- yl ester, Methyl-phenyl-carbamic acid 6-chloro-3- (2-chloro-6-fluoro-benzyl)-4-n-propy-2-oxo-2H- chromen-7-yl ester, Methyl-phenyl-carbamic acid 3- (4-methoxy-phenyl)-4-methyl-2-oxo-2H-chromen-7-yl ester, Methyl-phenyl-carbamic acid 4-methyl-2-oxo-3-phenyl-2H-chromen-7-yl ester, Methyl-phenyl-carbamic acid 3-(2, 5-dimethoxy-phenyl)-4-methyl-2-oxo-2H-chromen-7-yl es- ter, Methyl-phenyl-carbamic acid 3- (3, 4-dimethoxy-phenyl)-4-methyl-2-oxo-2H-chromen-7-yl es- ter, Methyl-phenyl-carbamic acid 4-pyrrolidine-1-yl-phenyl ester, Methyl-phenyl-carbamic acid 4-piperidine-1-yl-phenyl ester, Methyl-phenyl-carbamic acid 4-morpholine-1-yl-phenyl ester, Methyl-phenyl-carbamic acid 4-[(6-chloro-pyridine-3-carbonyl)-amino]-phenyl ester, Methyl-phenyl-carbamic acid 4-[(6-chloro-pyridine-3-carbonyl)-amino]-phenyl ester, Methyl-phenyl-carbamic acid 4-[(pyridine-2-carbonyl)-amino]-phenyl ester, 4-Chlor-phenyl-methyl-carbamic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester, 4-Chlor-phenyl-methyl-carbamic acid 4- (3, 5-dichloro-pyridin-2-yloxy)-phenyl ester, <BR> <BR> <BR> (4-Chloro-phenyl)-methyl-carbamic acid 4- (2-cyano-5-trifluoromethyl-pyridin-3-yloxy)-phenyl ester, Ethyl-phenyl-carbamic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester, Ethyl-phenyl-carbamic acid 4- (4-trifluoromethyl-phenoxy)-phenyl ester, Methyl-phenyl-carbamic acid pyrazol-1-yl ester, Methyl-phenyl-carbamic acid 4-bromo-pyrazol-1-yl ester,

Methyl-phenyl-carbamic acid 3,4, 5-tribromo-pyrazol-1-yl ester, Methyl-phenyl-carbamic acid 3- (4-methoxy-phenyl)-pyrazol-1-yl ester, Methyl-phenyl-carbamic acid imidazol-1-yl ester, Methyl-phenyl-carbamic acid [1, 2,3] triazol-1-yl ester, Methyl-phenyl-carbamic acid 3-bromo-pyrazol-1-yl ester, Methyl-phenyl-carbamic acid 5-bromo-pyrazol-1-yl ester, Methyl-phenyl-carbamic acid 3-chloro-pyrazol-1-yl ester, Methyl-phenyl-carbamic acid 4-chloro-pyrazol-1-yl ester, Methyl-phenyl-carbamic acid 5-chloro-pyrazol-1-yl ester, Methyl-phenyl-carbamic acid 4-iodo-pyrazol-1-yl ester, Methyl-phenyl-carbamic acid 5-iodo-pyrazol-1-yl ester, Methyl-phenyl-carbamic acid 3-methyl-pyrazol-1-yl ester, Methyl-phenyl-carbamic acid 4-methyl-pyrazol-1-yl ester, Methyl-phenyl-carbamic acid 5-methyl-pyrazol-1-yl ester, Methyl-phenyl-carbamic acid 4- (4-methoxy-phenyl)-pyrazol-1-yl ester, Methyl-phenyl-carbamic acid 5- (4-methoxy-phenyl)-pyrazol-1-yl ester, Methyl-phenyl-carbamic acid 3-(2-methoxy-phenyl)-pyrazol-1-yl ester, Methyl-phenyl-carbamic acid 3- (4-nitro-phenyl)-pyrazol-1-yl ester, Methyl-phenyl-carbamic acid 3-(2-nitro-phenyl)-pyrazol-1-yl ester, Methyl-phenyl-carbamic acid 3-pyridin-2-yl-pyrazol-1-yl ester, Methyl-phenyl-carbamic acid 4-pyridin-2-yl-pyrazol-1-yl ester, Methyl-phenyl-carbamic acid 3- (2-fluoro-phenyl)-pyrazol-1-yl ester, Methyl-phenyl-carbamic acid 4- (2-fluoro-phenyl)-pyrazol-1-yl ester, Methyl-phenyl-carbamic acid 5- (2-fluoro-phenyl)-pyrazol-1-yl ester, Methyl-phenyl-carbamic acid 3-phenylsulfanyl-pyrazol-1-yl ester, Methyl-phenyl-carbamic acid 4-phenylsulfanyl-pyrazol-1-yl ester, Methyl-phenyl-carbamic acid 5-phenylsulfanyl-pyrazol-1-yl ester, Methyl-phenyl-carbamic acid 4-thiophen-3-yl-pyrazol-1-yl ester, Methyl-phenyl-carbamic acid 3-thiophen-2-yl-pyrazol-1-yl ester, Methyl-phenyl-carbamic acid 4-thiophen-2-yl-pyrazol-1-yl ester, Methyl-phenyl-carbamic acid 5-thiophen-2-yl-pyrazol-1-yl ester, Methyl-phenyl-carbamic acid 2-chloro-imidazol-1-yl ester, Methyl-phenyl-carbamic acid 2-bromo-imidazol-1-yl ester, Methyl-phenyl-carbamic acid 2-iodo-imidazol-1-yl ester, Methyl-phenyl-carbamic acid 2-methyl-imidazol-1-yl ester,

Methyl-phenyl-carbamic acid 2-phenylsulfanyl-imidazol-1-yl ester, Methyl-phenyl-carbamic acid 2- (4-methoxy-phenyl)-imidazol-1-yl ester, Methyl-phenyl-carbamic acid 2- (4-fluoro-phenyl)-imidazol-1-yl ester, Methyl-phenyl-carbamic acid 2-thiophen-2-yl-imidazol-1-yl ester, Methyl-phenyl-carbamic acid 2-pyridin-2-yl-imidazol-1-yl ester, Methyl-phenyl-carbamic acid 2, 5-dichloro-imidazol-1-yl ester, Methyl-phenyl-carbamic acid 4-bromo-2, 5-dichloro-imidazol-1-yl ester, 4- (Methyl-phenyl-carbamoyloxy)-benzoic acid 2, 5-dioxo-pyrrolidin-1-yl ester, Methyl-phenyl-carbamic acid 4- (1, 3, 5-trimethyl-1 H-pyrazol-4-ylmethyl)-phenyl ester, Methyl-phenyl-carbamic acid 4- (2-cyano-ethyl)-phenyl ester, Methyl-phenyl-carbamic acid 4- ( [1, 2,3, 4] thiatriazol-5-ylamino)-phenyl ester, Methyl-phenyl-carbamic acid 4-pentyl-phenyl ester, Methyl-phenyl-carbamic acid 4- (2-methoxy-ethyl)-phenyl ester, Methyl-phenyl-carbamic acid 4-acetyl-phenyl ester, Methyl-phenyl-carbamic acid pyridin-4-yl ester, Methyl-phenyl-carbamic acid pyridin-3-yl ester, Methyl-phenyl-carbamic acid 6-methyl-pyridin-3-yl ester, Methyl-phenyl-carbamic acid isoquinolin-1-yl ester, Methyl-phenyl-carbamic acid 3-phenoxy-phenyl ester, Methyl-phenyl-carbamic acid 3-acetyl-phenyl ester, Methyl-phenyl-carbamic acid 4-acetyl-2-carbamoyl-phenyl ester, Methyl-phenyl-carbamic acid 4-acetyl-3-methyl-phenyl ester, Methyl-phenyl-carbamic acid 1-oxo-indan-4-yl ester, Methyl-phenyl-carbamic acid benzothiazol-2-yl ester, Methyl-phenyl-carbamic acid 5-oxo-5,6, 7, 8-tetrahydro-naphthalen-2-yl ester, Methyl-phenyl-carbamic acid benzo [d] isoxazol-3-yl ester, Methyl-phenyl-carbamic acid pyridin-2-yl ester, Methyl-phenyl-carbamic acid 1-(methyl-phenyl-carbamoyl)-1 H-benzimidazol-2-yl ester, Methyl-phenyl-carbamic acid 4-[(pyridine-3-carbonyl)-amino]-phenyl ester, Methyl-phenyl-carbamic acid 4- (3-pyridin-3-yl-acryloyl)-phenyl ester, Methyl-phenyl-carbamic acid 4- [3- (3, 4, 5-trimethoxy-phenyl)-acryloyl]-phenyl ester, Methyl-phenyl-carbamic acid 4-diethylcarbamoyl-2-methoxy-phenyl ester, Methyl-phenyl-carbamic acid 3-phenylcarbamoyl-phenyl ester, Methyl-phenyl-carbamic acid quinolin-7-yl ester, Methyl-phenyl-carbamic acid 4- (4-methyl-piperazine-1-carbonyl)-phenyl ester,

Methyl-phenyl-carbamic acid 3-acetylamino-phenyl ester, Methyl-phenyl-carbamic acid 4-benzoyl-phenyl ester, Methyl-phenyl-carbamic acid biphenyl-3-yl ester, Methyl-phenyl-carbamic acid 1 H-indol-4-yl ester, Methyl-phenyl-carbamic acid 5,6, 7, 8-tetrahydro-naphthalen-1-yl ester, Methyl-phenyl-carbamic acid 5-oxo-5,6, 7, 8-tetrahydro-naphthalen-1-yl ester, Methyl-phenyl-carbamic acid 1,3-dioxo-1, 3-dihydro-isobenzofuran-4-yl ester, Methyl-phenyl-carbamic acid 4- (5-chloro-pyridin-2-yloxy)-phenyl ester, Methyl-phenyl-carbamic acid 4-morpholin-4-yl-phenyl ester, Methyl-phenyl-carbamic acid 4- (5, 6-dichloro-1, 3-dioxo-1, 3-dihydro-isoindol-2-yl)-phenyl es- ter, Methyl-phenyl-carbamic acid 4- (2-phenoxy-acetylamino)-phenyl ester, Methyl-phenyl-carbamic acid 4- [2- (4-chloro-phenyl)-ethyl]-phenyl ester, Methyl-phenyl-carbamic acid 4-[(pyridine-2-carbonyl)-amino]-phenyl ester, Methyl-phenyl-carbamic acid 4- [methyl- (thiophene-2-carbonyl)-amino]-phenyl ester, Methyl-phenyl-carbamic acid 4-butyrylamino-phenyl ester, Methyl-phenyl-carbamic acid 4- (4, 6-dimethyl-pyrimidin-2-ylsulfanyl)-phenyl ester, Methyl-phenyl-carbamic acid 4-methanesulfonyl-phenyl ester, Methyl-phenyl-carbamic acid 4- [2- (3-oxo-1, 2,3, 4-tetrahydro-quinoxalin-2-yl)-acetylamino]- phenyl ester, Methyl-phenyl-carbamic acid 4-phenylacetyl-phenyl ester, Methyl-phenyl-carbamic acid 4- { [4- (methyl-phenyl-carbamoyloxy)-2-oxo-1, 2-dihydro- quinoline-3-carbonyl]-amino}-phenyl ester, Methyl-phenyl-carbamic acid 4- [ (4-hydroxy-2-oxo-1, 2-dihydro-quinoline-3-carbonyl)-amino]- phenyl ester, Methyl-phenyl-carbamic acid 4- (4-hydroxy-benzyl)-phenyl ester Methyl-phenyl-carbamic acid 4- (4-trifluoromethyl-benzylcarbamoyl)-phenyl ester, Methyl-phenyl-carbamic acid 4- (butyl-methyl-carbamoyl)-phenyl ester, Methyl-phenyl-carbamic acid 4- (methyl-phenethyl-carbamoyl)-phenyl ester, Methyl-phenyl-carbamic acid 4-[(pyridin-2-ylmethyl)-carbamoyl]-phenyl ester, Methyl-phenyl-carbamic acid 4- (2-pyridin-2-yl-ethylcarbamoyl)-phenyl ester, Methyl-phenyl-carbamic acid 4- (2-phenylamino-ethylcarbamoyl)-phenyl ester, Methyl-phenyl-carbamic acid 4- (3-methyl-butylcarbamoyl)-phenyl ester, Methyl-phenyl-carbamic acid 4- (3, 3-dimethyl-butylcarbamoyl)-phenyl ester, Methyl-phenyl-carbamic acid 4-[(tetrahydro-furan-2-ylmethyl)-carbamoyl]-phenyl ester,

Methyl-phenyl-carbamic acid 4-cyclohexylcarbamoyl-phenyl ester, Methyl-phenyl-carbamic acid 4-cyclopropylcarbamoyl-phenyl ester, Methyl-phenyl-carbamic acid 4- (cyclohexylmethyl-carbamoyl)-phenyl ester, Methyl-phenyl-carbamic acid 5-nitro-pyridin-2-yl ester, Methyl-phenyl-carbamic acid pyrimidin-2-yl ester, Methyl-phenyl-carbamic acid 7-chloro-quinolin-4-yl ester, Methyl-phenyl-carbamic acid quinolin-4-yl ester, Methyl-phenyl-carbamic acid 5-methyl-isoxazol-3-yl ester, Methyl-phenyl-carbamic acid quinoxalin-2-yl ester, Methyl-phenyl-carbamic acid 4-methyl-quinolin-2-yl ester, Methyl-phenyl-carbamic acid 3-methyl-quinoxalin-2-yl ester, Methyl-phenyl-carbamic acid 4, 6-dimethyl-pyrimidin-2-yl ester, Methyl-phenyl-carbamic acid isoquinolin-6-yl ester, Methyl-phenyl-carbamic acid quinolin-2-yl ester, Methyl-phenyl-carbamic acid isoquinolin-3-yl ester, Methyl-phenyl-carbamic acid 4-trifluoromethyl-pyrimidin-2-yl ester, Methyl-phenyl-carbamic acid 3-nitro-pyridin-2-yl ester, Methyl-phenyl-carbamic acid 5-chloro-pyridin-2-yl ester, Methyl-phenyl-carbamic acid 5-(2-nitro-phenyl)-pyrimidin-2-yl ester, Methyl-phenyl-carbamic acid 5-trifluoromethyl-pyridin-2-yl ester, Methyl-phenyl-carbamic acid 3-chloro-5-trifluoromethyl-pyridin-2-yl ester, Methyl-phenyl-carbamic acid 5-nitro-3-trifluoromethyl-pyridin-2-yl ester, Methyl-phenyl-carbamic acid 4, 5-dichloro-pyridazin-3-yl ester, Methyl-phenyl-carbamic acid 5-benzoylamino-pyridin-2-yl ester, Methyl-phenyl-carbamic acid 5- (cyclohexanecarbonyl-amino)-pyridin-2-yl ester, Methyl-phenyl-carbamic acid 4, 4-dimethyl-2, 6-dioxo-3, 4,5, 6-tetrahydro-2H- [1, 3'] bipyridinyl-6'- yl ester, Methyl-phenyl-carbamic acid 5-(2, 2-dimethyl-propionylamino)-pyridin-2-yl ester, Methyl-phenyl-carbamic acid 5- (2-cyclohexyl-acetylamino)-pyridin-2-yl ester, Methyl-phenyl-carbamic acid 5- (4-methoxy-phenoxy)-pyrimidin-2-yl ester, Methyl-phenyl-carbamic acid 5- (3, 4-dichloro-phenoxy)-pyrimidin-2-yl ester, Methyl-phenyl-carbamic acid 6-pyridin-2-ylmethyl-pyridazin-3-yl ester, Methyl-phenyl-carbamic acid 6- (4-methoxy-benzyl)-pyridazin-3-yl ester, Methyl-phenyl-carbamic acid 6- (2, 4-dichloro-benzyl)-pyridazin-3-yl ester, Methyl-phenyl-carbamic acid 4-iodo-pyrazol-1-yl ester,

Methyl-phenyl-carbamic acid benzotriazol-1-yl ester, Methyl-phenyl-carbamic acid [1,2, 3] triazolo [4,5-b] pyridin-3-yl ester, Methyl-phenyl-carbamic acid 3-(2-nitro-phenyl)-pyrazol-1-yl ester, Methyl-phenyl-carbamic acid 3- (4-nitro-phenyl)-pyrazol-1-yl ester, Methyl-phenyl-carbamic acid 3-pyridin-2-yl-pyrazol-1-yl ester, Methyl-phenyl-carbamic acid 3-thiophen-2-yl-pyrazol-1-yl ester, Methyl-phenyl-carbamic acid 3-(2-fluoro-phenyl)-pyrazol-1-yl ester, Methyl-phenyl-carbamic acid 3-bromo-pyrazol-1-yl ester, Methyl-phenyl-carbamic acid 5-iodo-pyrazol-1-yl ester, Methyl-phenyl-carbamic acid 2-chloro-imidazol-1-yl ester, Methyl-phenyl-carbamic acid 4- (4-methoxy-phenyl)-pyrazol-1-yl ester, Methyl-phenyl-carbamic acid 5-benzoyl-pyrazol-1-yl ester, Methyl-phenyl-carbamic acid 5- (4-methoxy-phenyl)-pyrazol-1-yl ester, Methyl-phenyl-carbamic acid 5- (4-dimethylamino-phenyl)-pyrazol-1-yl ester, Methyl-phenyl-carbamic acid 4, 5-diiodo-pyrazol-1-yl ester, Methyl-phenyl-carbamic acid 5-thiophen-2-yl-pyrazol-1-yl ester, Methyl-phenyl-carbamic acid 2- (4-methoxy-phenyl)-imidazol-1-yl ester, Methyl-phenyl-carbamic acid 2-methylsulfanyl-imidazol-1-yl ester, Methyl-phenyl-carbamic acid 3, 5-bis- (4-methoxy-phenyl)-pyrazol-1-yi ester, <BR> <BR> <BR> Methyl-phenyl-carbamic acid 4- (4-fluoro-phenyl)-5- (4-methoxy-phenyl)-3- (4-methylphenyl)- pyrazol-1-yl ester, Methyl-phenyl-carbamic acid 4-benzyl-5- (4-methoxy-phenyl)-3- (methylphenyl)-pyrazol-1-yl ester, Methyl-phenyl-carbamic acid 4-acetyl-pyrazol-1-yl ester, Methyl-phenyl-carbamic acid 2- (4-nitro-phenyl)-imidazol-1-yl ester, Methyl-phenyl-carbamic acid 2-chloro-5- (4-methylphenyl)-imidazol-1-yl ester, Methyl-phenyl-carbamic acid 4-formyl-pyrazol-1-yl ester, Methyl-phenyl-carbamic acid 4-hydroxymethyl-pyrazol-1-yl ester, Methyl-phenyl-carbamic acid 4-phenylethynyl-pyrazol-1-yl ester, Methyl-phenyl-carbamic acid 2-bromo-imidazol-1-yl ester, Methyl-phenyl-carbamic acid 2-phenylsulfanyl-imidazol-1-yl ester, Methyl-o-tolyl-carbamic acid 4- (trifluoromethyl-pyridin-2-yloxy)-phenyl ester, Methyl-m-tolyl-carbamic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester, (3-Chloro-phenyl)-methyl-carbamic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester, Methyl-p-tolyl-carbamic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester,

(3-Fluoro-phenyl)-methyl-carbamic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester, (3-Chloro-phenyl)-methyl-carbamic acid 4-trifluoromethyl-pyrimidin-2-yl ester, Methyl-m-tolyl-carbamic acid 4-trifluoromethyl-pyrimidin-2-yl ester, Methyl-phenyl-carbamic acid 5- (3, 3-dimethyl-butyrylamino)-pyridin-2-yl ester, Methyl-phenyl-carbamic acid 5-[(pyridine-2-carbonyl)-amino]-pyridin-2-yl ester, Methyl-phenyl-carbamic acid 2- (4, 4-dimethyl-2, 6-dioxo-piperidin-1-yl)-pyrimidin-5-yl ester, Methyl-phenyl-carbamic acid 5-bromo-pyrimidin-2-yl ester, Methyl-phenyl-carbamic acid 5-[(6-chloro-pyridine-3-carbonyl)-amino]-pyridin-2-yl ester, Methyl-phenyl-carbamic acid 5-(2, 2-dimethyl-propylcarbamoyl)-pyridin-2-yl ester, Methyl-phenyl-carbamic acid 6- (3, 4-dichloro-phenoxy)-pyridazin-3-yl ester, Methyl-phenyl-carbamic acid 2, 6-oxo-3, 4,5, 6-tetrahydro-2H- [1, 3'] bipyridinyl-6'-yl ester, Methyl-phenyl-carbamic acid 5- (2, 5-dioxo-pyrrolidin-1-yl)-pyridin-2-yl ester, Methyl-phenyl-carbamic acid 5- (4-trifluoromethyl-benzoylamino)-pyridin-2-yl ester, Methyl-phenyl-carbamic acid quinolin-6-yl ester, Methyl-phenyl-carbamic acid 5- (4-chloro-benzoylamino)-pyridin-2-yl ester, 4 Methyl-phenyl-carbamic acid 5- (4-methoxy-benzoylamino)-pyridin-2-yl ester, Methyl-phenyl-carbamic acid 4, 4-dimethyl-3, 4,5, 6-tetrahydro-2H- [1, 3'] bipyridinyl-6'-yl ester, Methyl-phenyl-carbamic acid 2-methyl-quinolin-6-yl ester, {2-[4-(Methyl-phenyl-carbamoyloxy)-phenyl]-ethyl}-carbamic acid ter-butyl ester, Methyl-phenyl-carbamic acid 4- (2-amino-ethyl) phenyl ester, Methyl-phenyl-carbamic acid 4- [2- (toluene-4-sulfonylamino)-ethyl]-phenyl ester, Methyl-phenyl-carbamic acid 4- [2- (5-dimethylamino-naphthalene-1-sulfonylamino)-ethyl]- phenyl ester, Methyl-phenyl-carbamic acid 4- [2- (3, 4-difluoro-benzenesulfonylamino)-ethyl]-phenyl ester, 2- {2- [4- (Methyl-phenyl-carbamoyloxy)-phenyl]-ethylsulfamoyl}-benzoic acid methyl ester, Methyl-phenyl-carbamic acid 4- [2- (2, 5-dichloro-thiophene-3-sulfonylamino)-ethyl]-phenyl es- ter, Methyl-phenyl-carbamic acid 4- [2- (5-pyridin-2-yl-thiophene-2-sulfonylamino)-ethyl]-phenyl ester, Methyl-phenyl-carbamic acid 4- [2- (l-methyl-1 H-imidazole-4-sulfonylamino)-ethyl]-phenyl es- ter, Methyl-phenyl-carbamic acid 4- [2- (5-chloro-1, 3-dimethyl-1 H-pyrazole-4-sulfonylamino)-ethyl]- phenyl, Methyl-phenyl-carbamic acid 4- [2- (4-nitro-benzenesulfonylamino)-ethyl]-phenyl ester, Methyl-phenyl-carbamic acid 4- [2- (6-chloro-imidazo [2, 1-b] thiazole-5-sulfonylamino)-ethyl]-

phenyl ester, <BR> <BR> <BR> <BR> Methyl-phenyl-carbamic acid 4-[2-(2-trifluoromethoxy-benzenesulfonylamino)-ethyl]-phenyl ester, Methyl-phenyl-carbamic acid 4-(2-dimethylaminosulfonylamino-ethyl)-phenyl ester" Methyl-phenyl-carbamic acid 4- (2-methanesulfonylamino-ethyl)-phenyl ester, <BR> <BR> <BR> <BR> Methyl-phenyl-carbamic acid 4- [2- (6-morpholin-4-yl-pyridine-3-sulfonylamino)-ethyl]-phenyl ester, Methyl-phenyl-carbamic acid 4- [2- (6-phenoxy-pyridine-3-sulfonylamino)-ethyl]-phenyl ester, Methyl-phenyl-carbamic acid 4- {2- [4- (4-methyl-piperazin-1-yl)-benzenesulfonylamino]-ethyl}- phenyl ester, Methyl-phenyl-carbamic acid 4- [2- (4-dimethylamino-benzenesulfonylamino)-ethyl]-phenyl ester, Methyl-phenyl-carbamic acid 4- {2- [4- (2-pyrrolidin-1-yl-ethoxy)-benzenesulfonylamino]-ethyl)- phenyl ester, Methyl-phenyl-carbamic acid 4- (2-cyclohexyl-ethylsulfamoyl)-phenyl ester, Methyl-phenyl-carbamic acid 4- (3-methyl-butylsulfamoyl)-phenyl ester, Methyl-phenyl-carbamic acid 4- (1, 1,3, 3-tetramethyl-butylcarbamoyl)-phenyl ester, Methyl-phenyl-carbamic acid 4-[(2-dimethylamino-ethyl)-methyl-carbamoyl]-phenyl ester, Methyl-phenyl-carbamic acid 4- (cyclopropylmethyl-carbamoyl)-phenyl ester, Methyl-phenyl-carbamic acid 4- (methyl-pyridin-3-ylmethyl-carbamoyl)-phenyl ester, Methyl-phenyl-carbamic acid 4- [ (1 H-benzimidazol-2-ylmethyl)-carbamoyl]-phenyl ester, Methyl-phenyl-carbamic acid 4- [2- (4-chloro-phenyl)-ethylcarbamoyl]-phenyl ester, Methyl-phenyl-carbamic acid 5-amino-pyridin-2-yl ester, Methyl-phenyl-carbamic acid 5-benzenesulfonylamino-pyridin-2-yl ester, 3, 3-Dimethyl-4-[6-(methyl-phenyl-carbamoyloxy)-pyridin-3-ylcar bamoyl]-butyric acid, 2, 2-Dimethyl-N- [6- (methyl-phenyl-carbamoyloxy)-pyridin-3-yl]-succinamic acid, Methyl-phenyl-carbamic acid 5- (3, 3-dimethyl-2, 5-dioxo-pyrrolidin-1-yl)-pyridin-2-yl ester, Methyl-phenyl-carbamic acid 5- [3, 3-dimethyl-5- (4-methyl-piperazin-1-yl)-5-oxo-pentanoylamino]- pyridin-2-yl ester, Methyl-phenyl-carbamic acid 5- [3, 3-dimethyl-4- (pyridin-3-ylcarbamoyl)-butyrylamino]-pyridin-2-yl ester, <BR> <BR> <BR> <BR> Methyl-phenyl-carbamic acid 5- (3, 3-dimethyl-5-morpholin-4-yl-5-oxo-pentanoylamino)-pyridin-2- yl ester, Methyl-phenyl-carbamic acid 5- [4- (2-dimethylamino-ethylcarbamoyl)-3, 3-dimethyl- butyrylamino]-pyridin-2-yl ester,

Methyl-phenyl-carbamic acid 4-iodo-phenyl ester, Methyl-phenyl-carbamic acid 4'-trifluoromethyl-biphenyl-4-yl ester, Methyl-phenyl-carbamic acid 4'-trifluoromethoxy-biphenyl-4-yl ester, Methyl-phenyl-carbamic acid 4-pyridin-3-yl-phenyl ester, Methyl-phenyl-carbamic acid 4- (5-chloro-thiophen-2-yl)-phenyl ester, Methyl-phenyl-carbamic acid 4'-benzylsulfamoyl-biphenyl-4-yl ester, Methyl-phenyl-carbamic acid 4-styryl-phenyl ester, Methyl-phenyl-carbamic acid 4-phenylethynyl-phenyl ester, 3- [4- (Methyl-phenyl-carbamoyloxy)-phenyl]-acrylic acid methyl ester, Methyl-phenyl-carbamic acid 4- (toluene-4-sulfonylamino)-phenyl ester, Methyl-phenyl-carbamic acid 4- (5-pyridin-2-yl-thiophene-2-sulfonylamino)-phenyl ester, Methyl-phenyl-carbamic acid 4- (1-methyl-1 H-imidazole-4-sulfonylamino)-phenyl ester, Methyl-phenyl-carbamic acid 4- (2, 5-dichloro-thiophene-3-sulfonylamino)-phenyl ester, Methyl-phenyl-carbamic acid 4- (5-chloro-1, 3-dimethyl-1 H-pyrazole-4-sulfonylamino)-phenyl ester, Methyl-phenyl-carbamic acid 4- (5-dimethylamino-naphthalene-1-sulfonylamino)-phenyl ester, 2- [4- (Methyl-phenyl-carbamoyloxy)-phenylsulfamoyl]-benzoic acid methyl ester, Methyl-phenyl-carbamic acid 4- (3, 4-difluoro-benzenesulfonylamino)-phenyl ester, Methyl-phenyl-carbamic acid 4-pyridin-2-ylmethyl-phenyl ester, Methyl-phenyl-carbamic acid 4-pyridin-3-ylmethyl-phenyl ester, Methyl-phenyl-carbamic acid 4- (4-trifluoromethyl-benzyl)-phenyl ester, Methyl-phenyl-carbamic acid 4-thiophen-3-ylmethyl-phenyl ester, Methyl-phenyl-carbamic acid 4-thiophen-2-ylmethyl-phenyl ester, Methyl-phenyl-carbamic acid 4- [2- (4-amino-benzenesulfonylamino)-ethyl]-phenyl ester, Methyl-phenyl-carbamic acid 4-{2-[(pyridine-3-carbonyl)-amino]-ethyl}-phenyl ester, Methyl-phenyl-carbamic acid 4- [2- (2-dimethylamino-acetylamino)-ethyl]-phenyl ester, Methyl-phenyl-carbamic acid 2-(toluene-4-sulfonyl)-1, 2, 3, 4-tetrahydro-isoquinolin-7-yl ester, Methyl-phenyl-carbamic acid 4- [4- (2-pyrrolidin-1-yl-ethoxy)-benzyl]-phenyl ester, Methyl-phenyl-carbamic acid 2- [4- (2-pyrrolidin-1-yi-ethoxy)-benzenesulfonyl]-1, 2,3, 4- tetrahydro-isoquinolin-7-yl ester, Methyl-phenyl-carbamic acid 4- {2- [ (1-methyl-piperidine-4-carbonyl)-amino]-ethyl}-phenyl es- ter, Methyl-phenyl-carbamic acid 2- (3, 4-difluoro-benzenesulfonyl)-1, 2,3, 4-tetrahydro-isoquinolin- 7-yl ester, Methyl-phenyl-carbamic acid 1-methyl-2- (toluene-4-sulfonyl)-1, 2,3, 4-tetrahydro-isoquinolin-7-

yl ester, Methyl-phenyl-carbamic acid 2- [4- (4-methyl-piperazin-1-yl)-benzenesulfonyl]-1, 2,3, 4- tetrahydro-isoquinolin, Methyl-phenyl-carbamic acid 1-methyl-2- [4- (4-methyl-piperazin-1-yl)-benzenesulfonyl]- 1,2, 3, 4-tetrahydro-isoquinolin-7-yl ester, 3, 3-Dimethyl-4- {2- [4- (methyl-phenyl-carbamoyloxy)-phenyl]-ethylcarbamoyl}-butyric acid, <BR> <BR> <BR> Methyl-phenyl-carbamic acid 4- {2- [4- (4-methyl-piperazin-1-yl)-benzoylamino]-ethyl}-phenyl ester, <BR> <BR> <BR> Methyl-phenyl-carbamic acid 4- {2- [4- (4-methyl-piperazin-1-ylmethyl)-benzoylamino]-ethyl}- phenyl ester, Methyl-phenyl-carbamic acid 4- [2- (4, 4-dimethyl-2, 6-dioxo-piperidin-1-yl)-ethyl]-phenyl ester, 3, 3-Dimethyl-4- {2- [4- (methyl-phenyl-carbamoyloxy)-phenyl]-ethylcarbamoyl}-butyric acid ethyl ester, Methyl-phenyl-carbamic acid 4-hydroxymethyl-phenyl ester, Methyl-phenyl-carbamic acid 4- (2-hydroxy-ethyl)-phenyl ester, Methyl-phenyl-carbamic acid 4- (4-dimethylamino-pyridin-2-ylmethyl)-phenyl ester, Methyl-phenyl-carbamic acid 4- (4-imidazol-1-yl-phenoxymethyl)-phenyl ester, Methyl-phenyl-carbamic acid 4- [4- (2-dimethylamino-ethyl)-phenoxymethyl]-phenyl ester, Methyl-phenyl-carbamic acid 4-(pyrazol-1-yloxymethyl)-phenyl ester, Methyl-phenyl-carbamic acid 4- (imidazol-1-yloxymethyl)-phenyl ester, Methyl-phenyl-carbamic acid 4- (2-oxo-2H-pyridin-1-ylmethyl)-phenyl ester, Methyl-phenyl-carbamic acid 4-[2-(pyridin-2-yloxy)-ethyl]-phenyl ester, Methyl-phenyl-carbamic acid 4- [2- (4-imidazol-1-yl-phenoxy)-ethyl]-phenyl ester, Methyl-phenyl-carbamic acid 4- {2- [4- (2-dimethylamino-ethyl)-phenoxy]-ethyl}-phenyl ester, Methyl-phenyl-carbamic acid 4- [2- (pyrazol-1-yloxy)-ethyl]-phenyl ester, Methyl-phenyl-carbamic acid 4- [2- (imidazol-1-yloxy)-ethyl]-phenyl ester, Methyl-phenyl-carbamic acid 4- (5-methyl-pyridin-2-ylmethyl)-phenyl ester, Methyl-phenyl-carbamic acid 4- (4-oxo-4H-pyridin-1-ylmethyl)-phenyl ester, Methyl-phenyl-carbamic acid 4- [2- (pyridin-3-yloxy)-ethyl]-phenyl ester, Methyl-phenyl-carbamic acid 4- (2-oxo-2H-pyridin-1-ylmethyl)-phenyl ester, Methyl-phenyl-carbamic acid 4- (pyridin-3-yloxymethyl)-phenyl ester, Methyl-phenyl-carbamic acid 4-[2-(2, 5-dioxo-pyrrolidin-1-yl)-ethyl]-phenyl ester, Methyl-phenyl-carbamic acid 4- [2- (1, 3-dioxo-1, 3-dihydro-pyrrolo [3, 4lpyridin-2-yl)-ethyl]- phenyl ester, Methyl-phenyl-carbamic acid 4- (1-methyl-1 H-imidazol-2-ylsulfanylmethyl)-phenyl ester,

Methyl-phenyl-carbamic acid 4-tetrazol-1-ylmethyl-phenyl ester, Methyl-phenyl-carbamic acid 4- (2, 5-dioxo-pyrrolidin-1-ylmethyl)-phenyl ester, Methyl-phenyl- carbamic acid 4-[2-(2-thioxo-2H-pyridin-1-yl)-ethyl]-phenyl ester, Methyl-phenyl-carbamic acid 4- (1, 3-dioxo-1, 3-dihydro-pyrrolo [3,4) pyridin-2-ylmethyl)-phenyl ester, Methyl-phenyl-carbamic acid 4- [1, 2, 4] triazol-1-ylmethyl-phenyl ester, Methyl-phenyl-carbamic acid 4- (2-thioxo-2H-pyridin-1-ylmethyl)-phenyl ester, Methyl-phenyl-carbamic acid 4- [2- (1-methyl-1 H-imidazol-2-ylsulfanyl)-ethyl]-phenyl ester, Ethyl-phenyl-carbamic acid 4-(2-tetrazol-1-yl-ethyl)-phenyl ester, Methyl-phenyl-carbamic acid 4-[2-(pyrimidin-2-yloxy)-ethyl]-phenyl ester, Methyl-phenyl-carbamic acid 4-[2-(pyridin-4-ylsulfanyl)-ethyl]-phenyl ester, Methyl-phenyl-carbamic acid 4- [2- (l-pyridin-3-yl-l H-imidazol-2-ylsulfanyl)-ethyl]-phenyl ester, and Methyl-phenyl-carbamic acid 4- [2- (1, 3-dioxo-1, 3-dihydro-isoindol-2-yl)-ethyl]-phenyl ester.

Further examples of specific compounds of the invention are: Benzyl-methyl-carbamic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester, and Benzyl-methyl-carbamic acid 4- (3, 5-dichloro pyridin-2-yloxy)-phenyl ester.

Further examples of specific compounds of the invention are: Isopropyl-methyl-carbamic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester, Cyclohexyl-methyl-carbamic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester.

Dimethyl-carbamic acid 4- (3, 5-dichloro pyridin-2-yloxy)-phenyl ester, Methyl-pyridin-2-yl-carbamic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester, (2-Dimethylamino-ethyl) methylcarbamic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl es- ter, (6-Methoxy-pyridin-2-yl)-methyl-carbamic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester, (4-Methoxy-phenyl)-methyl-carbamic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester, (2-Methoxy-phenyl)-methyl-carbamic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester, (2-Carbamoyl-4-chloro-phenyl)-methyl-carbamic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)- phenyl ester, (2-Carbamoyl-phenyl)-methyl-carbamic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl es- ter, (2-Chloro-phenyl)-methyl-carbamic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester,

(2, 4-Difluoro-phenyl)-methyl-carbamic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester, and <BR> Methyl- (2-trifluoromethoxy-phenyl)-carbamic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester.

Further examples of specific compounds of the invention are: Pyrrolidine1-carboxylic acid 4- (3, 5-dichloro-pyridin-2-yloxy)-phenyl ester, 2, 3-Dihydro-indole-1-carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester. and 1, 3-Dihydro-isoindole-2-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester.

Further examples of specific compounds of the invention are: Piperidine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester, Piperidine-1-carboxylic acid 3- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester, Piperidine-1-carboxylic acid 4- (3, 5-dichloro-pyridin-2-yloxy)-phenyl ester, Piperidine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-ylamino)-phenyl ester, Piperidine-1-carboxylic acid 4- (3, 5-dichloro-pyridin-4-yloxy)-phenyl ester, Piperidine-1-carboxylic acid 4- (4-trifluoromethyl-phenoxy)-phenyl ester, Piperidine-1-carboxylic acid 4- (2-cyano-5-trifluoromethyl-pyridine-3-yloxy)-phenyl ester, Piperidine-1-carboxylic acid 2-benzenesulfonyl-4- (3-chloro-5-trifluoromethyl-pyridine-2- yloxy)-phenyl ester, Piperidine-1-carboxylic acid 4-tert-butoxy-phenyl ester, Piperidine-1-carboxylic acid 3- (4-fluorobenzyl)-4-methyl-2-oxo-2H-chromen-7-yl ester, Piperidine-1-carboxylic acid 4-phenoxy-phenyl ester, Piperidine-1-carboxylic acid 4- (4-chlorobenzoyl)-phenyl ester, Piperidine-1-carboxylic acid 4- (3-chloro-5-trifluoromethyl)-pyridine-2-yloxy)-phenyl ester, Piperidine-1-carboxylic acid 4-[4-(4-chloro-phenyl)-thiazol-2-yl]-phenyl ester, Piperidine-1-carboxylic acid 4-pyrrol-1-yl-phenyl ester, Piperidine-1-carboxylic acid 4-imidazol-1-yl-phenyl ester, Piperidine-1-carboxylic acid 4- (3-chloro-5-trifluoromethyl)-pyridine-2-ylmethyl)-phenyl ester, Piperidine-1-carboxylic acid 4-trifluoromethylsulfanyl-phenyl ester, Piperidine-1-carboxylic acid 4-pentafluoromethyloxy-phenyl ester, Piperidine-1-carboxylic acid 4-benzyloxy-phenyl ester, Piperidine-1-carboxylic acid 4-benzyl-phenyl ester, Piperidine-1-carboxylic acid 4'-cyano-biphenyl-4-yl-ester, Piperidine-1-carboxylic acid 4'-bromo-biphenyl-4-yl-ester,

Piperidine-1-carboxylic acid biphenyl-4-yl-ester, Piperidine-1-carboxylic acid 4- [3- (4-chlorophenyl)-ureido]-phenyl ester, Piperidine-1-carboxylic acid 4- (4-nitro-phenoxy)-phenyl ester, Piperidine-1-carboxylic acid 4-heptylsulfanyl-phenyl ester, Piperidine-1-carboxylic acid 4-butoxy-phenyl ester, Piperidine-1-carboxylic acid 4- (4-chloro-benzenesulfonyl)-phenyl ester, Piperidine-1-carboxylic acid 4- (4-chloromethyl-thiazol-2-yl)-phenyl ester, Piperidine-1-carboxylic acid 4- (4, 4-dimethyl-2, 6-dioxo-piperidin-1-yl)-phenyl ester, cis-Piperidine-1-carboxylic acid 4-(1,3-dioxo-octahydro-isoindol-2-yl)-phenyl ester, Piperidine-1-carboxylic acid 4- (cyclohexanecarbonyl-amino)-phenyl ester, Piperidine-1-carboxylic acid 4- (2-cyclohexyl-acetylamino)-phenyl ester, cis/trans-Piperidine-1-carboxylic acid 4- [ (4-tert-butyl-cyclohexanecarbonyl)-amino]-phenyl ester, cis-Piperidine-1-carboxylic acid 4- [ (4-tert-butyl-cyclohexanecarbonyl)-amino]-phenyl ester, trans- Piperidine-1-carboxylic acid 4- [ (4-tert-butyl-cyclohexanecarbonyl)-amino]-phenyl ester, Piperidine-1-carboxylic acid 4- (3, 3-dimethyl-butyrylamino)-phenyl ester, Piperidine-1-carboxylic acid 3-benzyl-4-methyl-2-oxo-2H-chromen-7-yl ester, Piperidine-1-carboxylic acid 3- (3, 4-dichloro-benzyl)-4-methyl-2-oxo-2H-chromen-7-yl ester, Piperidine-1-carboxylic acid 3- (2-chloro-6-fluoro-benzyl)-4-methyl-2-oxo-2H-chromen-7-yl ester, Piperidine-1-carboxylic acid 3-(2,6-dichloro-benzyl)-4-methyl-2-oxo-2H-chromen-7-yl ester, Piperidine-1-carboxylic acid 3- (2, 6-dichloro-benzyl)-6-chloro-4-methyl-2-oxo-2H-chromen-7-yl ester, Piperidine-1-carboxylic acid 6-chloro-3- (2-chloro-6-fluoro-benzyl)-4-n-propy-2-oxo-2H- chromen-7-yl ester, Piperidine-1-carboxylic acid 3- (4-methoxy-phenyl)-4-methyl-2-oxo-2H-chromen-7-yl ester, Piperidine-1-carboxylic acid 4-methyl-2-oxo-3-phenyl-2H-chromen-7-yl ester, Piperidine-1-carboxylic acid 3-(2,5-dimethoxy-phenyl)-4-methyl-2-oxo-2H-chromen-7-yl ester, Piperidine-1-carboxylic acid 3- (3, 4-dimethoxy-phenyl)-4-methyl-2-oxo-2H-chromen-7-yl ester, Piperidine-1-carboxylic acid 4-pyrrolidine-1-yl-phenyl ester, Piperidine-1-carboxylic acid 4-piperidine-1-yl-phenyl ester, Piperidine-1-carboxylic acid 4-morpholine-1-yl-phenyl ester, Piperidine-1-carboxylic acid 4-[(6-chloro-pyridine-3-carbonyl)-amino]-phenyl ester, Piperidine-1-carboxylic acid 4-[(6-chloro-pyridine-3-carbonyl)-amino]-phenyl ester, Piperidine-1-carboxylic acid 4-[(pyridine-2-carbonyl)-amino]-phenyl ester,

Piperidine-1-carboxylic acid pyrazol-1-yl ester, Piperidine-1-carboxylic acid 3-bromo-pyrazol-1-yl ester, Piperidine-1-carboxylic acid 4-bromo-pyrazol-1-yl ester, Piperidine-1-carboxylic acid 5-bromo-pyrazol-1-yl ester, Piperidine-1-carboxylic acid 3,4, 5-tribromo-pyrazol-1-yl ester, Piperidine-1-carboxylic acid 4-chloro-pyrazol-1-yl ester, Piperidine-1-carboxylic acid 4-iodo-pyrazol-1-yl ester, Piperidine-1-carboxylic acid 3- (4-methoxy-phenyl)-pyrazol-1-yl ester, Piperidine-1-carboxylic acid 3-(2-methoxy-phenyl)-pyrazol-1-yl ester, Piperidine-1-carboxylic acid 3- (4-nitro-phenyl)-pyrazol-1-yl ester, Piperidine-1-carboxylic acid 3- (2-fluoro-phenyl)-pyrazol-1-yl ester, Piperidine-1-carboxylic acid 3-pyridin-2-yl-pyrazol-1-yl ester, Piperidine-1-carboxylic acid 4-phenylsulfanyl-pyrazol-1-yl ester, Piperidine-1-carboxylic acid 3-thiophen-2-yl-pyrazol-1-yl ester, Piperidine-1-carboxylic acid 5-thiophen-2-yl-pyrazol-1-yl ester, Piperidine-1-carboxylic acid imidazol-1-yl ester, Piperidine-1-carboxylic acid 2-chloro-imidazol-1-yl ester, Piperidine-1-carboxylic acid 2-bromo-imidazol-1-yl ester, Piperidine-1-carboxylic acid 2-iodo-imidazol-1-yl ester, Piperidine-1-carboxylic acid 2-methyl-imidazol-1-yl ester, Piperidine-1-carboxylic acid 2-phenylsulfanyl-imidazol-1-yl ester, Piperidine-1-carboxylic acid 2- (4-methoxy-phenyl)-imidazol-1-yl ester, Piperidine-1-carboxylic acid 2- (4-fluoro-phenyl)-imidazol-1-yl ester, Piperidine-1-carboxylic acid 2-thiophen-2-yl-imidazol-1-yl ester, Piperidine-1-carboxylic acid 2-pyridin-2-yl-imidazol-1-yl ester, Piperidine-1-carboxylic acid 2, 5-dichloro-imidazol-1-yl ester, Piperidine-1-carboxylic acid 4-bromo-2, 5-dichloro-imidazol-1-yl ester, 2-Methyl-piperidine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester, 3-Methyl-piperidine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester, 4-Methyl-piperidine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester, 4-Benzyl-piperidine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester, 1,4-Dioxa-8-aza-spiro [4.5] decane-8-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)- phenyl ester, 3-Hydroxy-piperidine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester, 3, 4-Dihydro-1 H-isoquinoline-2-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl es-

ter, 3, 4-Dihydro-2H-quinoline-1-carboxylic acid 4- (3, 5-dichloro-pyridin-2-yloxy)-phenyl ester, 3, 4-Dihydro-2H-quinoline-1-carboxylic acid 4- (2-cyano-5-trifluoromethyl-pyridin-3-yloxy)- phenyl ester, 3, 4-Dihydro-2H-quinoline-1-carboxylic acid 3- (3, 4-dichloro-benzyl)-4-methyl-2-oxo-2H- chromen-7-yl ester, 3, 4-Dihydro-2H-quinoline-1-carboxylic acid 3-benzyl-4-methyl-2-oxo-2H-chromen-7-yl ester, 3, 4-Dihydro-2H-quinoline-1-carboxylic acid 3- (2-chloro-6-fluoro-benzyl)-4-methyl-2-oxo-2H- chromen-7-yl ester, 3, 4-Dihydro-2H-quinoline-1-carboxylic acid 3- (2, 6-dichloro-benzyl)-4-methyl-2-oxo-2H- chromen-7-yl ester, 3, 4-Dihydro-2H-quinoline-1-carboxylic acid 3- (2, 6-dichloro-benzyl)-6-chloro-4-methyl-2-oxo- 2H-chromen-7-yl ester, 3, 4-Dihydro-2H-quinoline-1-carboxylic acid 3- (4-fluoro-benzyl)-4-methyl-2-oxo-2H-chromen- 7-yl ester, 3, 4-Dihydro-2H-quinoline-1-carboxylic acid 6-chloro-3- (2-chloro-6-fluoro-benzyl)-4-n-propy-2- oxo-2H-chromen-7-yl ester, 3, 4-Dihydro-2H-quinoline-1-carboxylic acid 3-(4-methoxy-phenyl)-4-methyl-2-oxo-2H- chromen-7-yl ester, 3, 4-Dihydro-2H-quinoline-1-carboxylic acid 4-methyl-2-oxo-3-phenyl-2H-chromen-7-yl ester, 3, 4-Dihydro-2H-quinoline-1-carboxylic acid 3-(2,5-dimethoxy-phenyl)-4-methyl-2-oxo-2H- chromen-7-yl ester, 3, 4-Dihydro-2H-quinoline-1-carboxylic acid 3- (3, 4-dimethoxy-phenyl)-4-methyl-2-oxo-2H- chromen-7-yl ester, 7-Trifluoromethyl-3, 4-dihydro-2H-quinoline-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2- yloxy)-phenyl ester, 4-Hydroxymethyl-piperidine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl es- ter, 4-Oxo-piperidine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester, 4-[5-(4-Dimethylamino-phenyl)-1H-pyrazol-3-yl]-piperidine-1- carboxylic acid 4- (5- trifluoromethyl-pyridin-2-yloxy)-phenyl ester, 4-(5-Furan-2-yl-1H-pyrazol-3-yl)-piperidine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2- yloxy)-phenyl ester, 4-Benzylamino-piperidine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester, 4- (3, 4-Dihydro-1 H-isoquinolin-2-ylmethyl)-piperidine-1-carboxylic acid 4- (5-trifluoromethyl-

pyridin-2-yloxy)-phenyl ester, 3-Hydroxymethyl-piperidine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl es- ter, 3-Hydroxy-piperidine-1-carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester, 4-Benzyl-4-hydroxy-piperidine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester, 4-Hydroxy-piperidine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester, 4-Pyrrolidin-1-yl-piperidine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl es- ter, 4-Hydroxymethyl-piperidine-1-carboxylic acid 4- (5-chloro-pyridin-2-yloxy)-phenyl ester, 1, 4-Dioxa-8-aza-spiro [4.5] decane-8-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)- phenyl ester, 4-Benzoyl-piperidine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester, [1,4'] Bipiperidinyl-1'-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester, 4-(2-Oxo-2, 3-dihydro-benzimidazol-1-yl)-piperidine-1-carboxylic acid 4- (5-trifluoromethyl- pyridin-2-yloxy)-phenyl ester, 3-Diethylcarbamoyl-piperidine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester, 4-Carbamoyl-piperidine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester, 3-Carbamoyl-piperidine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester, 4-(tert-Butyl-dimethyl-silanyloxy)-piperidine-1-carboxylic acid 5-benzoylamino-pyridin-2-yl es- ter, 4-Hydroxy-piperidine-1-carboxylic acid 5-benzoylamino-pyridin-2-yl ester, 4-Hydroxy-piperidine-1-carboxylic acid 5-trifluoromethyl-pyridin-2-yl ester, 4-Hydroxy-piperidine-1-carboxylic acid 5- (4-chloro-benzoylamino)-pyridin-2-yl ester, 4-Hydroxy-piperidine-1-carboxylic acid 5- (3-methoxy-benzoylamino)-pyridin-2-yl ester, 4-Hydroxy-piperidine-1-carboxylic acid 5-(4-methoxy-benzoylamino)-pyridin-2-yl ester, 4-Hydroxy-piperidine-1-carboxylic acid 5- (2, 4-dichloro-benzoylamino)-pyridin-2-yl ester, 4-Hydroxy-piperidine-1-carboxylic acid 5- (4-trifluoromethyl-benzoylamino)-pyridin-2-yl ester, 4-Hydroxy-piperidine-1-carboxylic acid 4, 4-dimethyl-2, 6-dioxo-3,4, 5,6-tetrahydro-2H- [1,3'] bipyridinyl-6'-yl ester, 4-Hydroxy-piperidine-1-carboxylic acid 5- (5-trifluoromethyl-pyridin-2-yloxy)-pyridin-2-yl ester, 4-Hydroxy-piperidine-1-carboxylic acid 5-(3,5-dichloro-pyridin-2-yloxy)-pyridin-2-yl ester, 4-Aminomethyl-piperidine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester, 4-Benzimidazol-1-yl-piperidine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl

ester, 4-Hydroxymethyl-piperidine-1-carboxylic acid 4- (2-cyclohexyl-acetylamino)-phenyl ester, 4- (4-Amino-phenyl)-piperidine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester, <BR> <BR> <BR> <BR> 4- (Methyl-pyridin-3-ylmethyl-amino)-piperidine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin- 2-yloxy)-phenyl ester, 4- (2-Oxo-pyrrolidin-1-yl)-piperidine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)- phenyl ester, <BR> <BR> <BR> 4- (Methyl-phenethyl-amino)-piperidine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)- phenyl ester, 4-[(Benzyl-ethyl-amino)-methyl]-piperidine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2- yloxy)-phenyl ester, 4-[Methyl-phenethyl-amino)-methyl]-piperidine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin- 2-yloxy)-phenyl ester, 4-[(CycloheXyl-methyl-amino)-methyl]-piperidine-1-carboxylic acid 4- (5-trifluoromethyl- pyridin-2-yloxy)-phenyl ester, 4-[(Ethyl-pyridin-4-ylmethyl-amino)-methyl]-piperidine-1-car boxylic acid 4- (5-trifluoromethyl- pyridin-2-yloxy)-phenyl ester, 4-[(Benzyl-methyl-amino)-methyl]-piperidine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2- yloxy)-phenyl ester, 4-[(Methyl-pyridin-3-ylmethyl-amino)-methyl]-piperidine-1-ca rboxylic acid 4-(5-trifluoromethyl- pyridin-2-yloxy)-phenyl ester, 4-(1,3-Dihydro-isoindol-2-ylmethyl)-piperidine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2- yloxy)-phenyl ester, 4-Benzotriazol-1-yl-piperidine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester, <BR> <BR> <BR> <BR> 4-[(Cyclopropylmethyl-amino)-methyl]-piperidine-1-carboxylic acid 4-(5-trifluoromthyl-pyridin- 2-yloxy)-phenyl ester, 4- [Methyl- (2-pyridin-2-yl-ethyl)-amino]-piperidine-1-carboxylic acid 4- (5-trifluoromethyl- pyridin-2-yloxy)-phenyl ester, 4- (Cyclohexyl-methyl-amino)-piperidine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2- yloxy)-phenyl ester, <BR> <BR> <BR> 4- (Isopropyl-methyl-amino)-piperidine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)- phenyl ester, 4-Hydroxymethyl-piperidine-1-carboxylic acid 4- (3, 3-dimethyl-butylcarbamoyl)-phenyl ester

ester, Piperidine-1-carboxylic acid 4, 4-dimethyl-2, 6-dioxo-3,4, 5, 6-tetrahydro-2H-[1,3']bipyridinyl-6'-yl, 4-[Methyl-(2-pyridin-4-yl-ethyl)-amino]-piperidine-1-carboxy lic acid 4- (5-trifluoromethyl- pyridin-2-yloxy)-phenyl ester, 4-(Cyclopropyl-pyridin-4-ylmethyl-amino)-piperidine-1-carbox ylic acid 4- (5-trifluoromethyl- pyridin-2-yloxy)-phenyl ester, 4-[Cyclopropyl-(2-fluoro-benzyl)-amino]-piperidine-1-carboxy lic acid 4- (5-trifluoromethyl- pyridin-2-yloxy)-phenyl ester, 4-(Cyclopropyl-pyridin-3-ylmethyl-amino)-piperidine-1-carbox ylic acid 4- (5-trifluoromethyl- pyridin-2-yloxy)-phenyl ester, 4-(Cyclopropylmethyl-pyridin-3-ylmethyl-amino)-piperidine-1- carboxylic acid 4- (5- trifluoromethyl-pyridin-2-yloxy)-phenyl ester, 4-(Cyclopropylmethyl-pyridin-3-ylmethyl-amino)-piperidine-1- carboxylic acid 4- (5- trifluoromethyl-pyridin-2-yloxy)-phenyl ester, 4- (4-Hydroxy-piperidin-1-ylmethyl)-piperidine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2- yloxy)-phenyl ester, 4- {3- [1- (2-Hydroxy-ethyl)-piperidin-4-yl]-propyl}-piperidine-1-carbo xylic acid 4- (5- trifluoromethyl-pyridin-2-yloxy)-phenyl ester, 4-(2-Pyrrolidin-1-yl-ethyl)-piperidine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)- phenyl ester, 4-Hydroxy-piperidine-1-carboxylic acid 4- [2- (toluene-4-sulfonylamino)-ethyl]-phenyl ester, 4-Hydroxy-piperidine-1-carboxylic acid 4-[2-(5-pyridin-2-yl-thiophene-2-sulfonylamino)-ethyl]- phenyl, 4-Hydroxy-piperidine-1-carboxylic acid 4- (5-pyridin-2-yl-thiophene-2-sulfonylamino)-phenyl ester, 4-Hydroxy-piperidine-1-carboxylic acid 4-pyridin-2-ylmethyl-phenyl ester, 4-Hydroxy-piperidine-1-carboxylic acid 4-pyridin-3-ylmethyl-phenyl ester, 4-Hydroxy-piperidine-1-carboxylic acid 4- (4-trifluoromethyl-benzyl)-phenyl ester, 4-Hydroxy-piperidine-1-carboxylic acid 4- (5-methyl-pyridin-2-ylmethyl)-phenyl ester, 4- (3-Amino-phenyl)-piperidine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin2-yloxy)-phenyl es- ter, 4-Phenyl-piperidine-1-carboxylic acid 4- (5-methyl-pyridin-2-ylmethyl)-phenyl ester, and 4- (4-Methoxy-phenyl)-3, 6-dihydro-2H-pyridine-l-carboxylic acid 4- (5-methyl-pyridin-2- ylmethyl)-phenyl ester.

Further examples of specific compounds of the invention are :

4-Methyl-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester, 4-Benzyl-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester, 4-(2-Hydroxyethyl)-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester, 4-(Pyridin-2-yl)-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester, 4- (Pyrrolidinocarbonylmethyl)- piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2- yloxy)-phenyl ester, 4-Phenyl-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester, 4- (Isopropylaminocarbonylmethyl)-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2- yloxy)-phenyl ester, 4-Ethyl-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester, 4-Propyl-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester, 4-Butyl-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester, 4- (4-Chlorobenzyl)-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester, 4- (4-Chlorophenyl)-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester, 4-(Diphenylmethyl)-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester, 4-(3-Hydroxypropyl)-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester, 4-(3-Trifluoromethylphenyl)-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)- phenyl ester, 4-(3-Chlorophenyl)-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester, 4-(2-Chlorophenyl)-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester, 4-(3,4-Dichlorophenyl)-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)- phenyl ester, 4-(4-Fluorophenyl)-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester, 4- (4-Methoxyphenyl)-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester, 4-(3-Methoxyphenyl)-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl

ester, 4-(2-Methoxyphenyl)-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester, 4-(2,4-Dimethoxyphenyl)-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)- phenyl ester, 4- (3, 4, 5-Trimethoxyphenyl)-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)- phenyl ester, <BR> <BR> <BR> <BR> 4- [3- (Trifluoromethyl) pyridin-2-yl]-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2- yloxy)-phenyl ester, 4-(3,4-Methylenedioxy-phenyl)-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2- yloxy)-phenyl ester, 4-(3,4-Methylenedioxy-phenyl)-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2- yloxy)-phenyl ester, 4-(Pyridin-4-yl)-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester, 4-Cyclopentyl-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester, 4-(2-Pyrimidinyl)-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl es- ter, 4- (4-Acetylphenyl)-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester, 4-(2-(2-Hydroxyethoxy)ethyl)-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2- yloxy)-phenyl ester, 4-Benzyl-piperazine-1-carboxylic acid pyrazol-1-yl ester, 4-Benzyl-piperazine-1-carboxylic acid 3-bromo-pyrazol-1-yl ester, 4-Benzyl-piperazine-1-carboxylic acid 4-bromo-pyrazol-1-yl ester, 4-Benzyl-piperazine-1-carboxylic acid 5-bromo-pyrazol-1-yl ester, 4-Benzyl-piperazine-1-carboxylic acid 3,4, 5-tribromo-pyrazol-1-yl ester, 4-Benzyl-piperazine-1-carboxylic acid 4-chloro-pyrazol-1-yl ester, 4-Benzyl-piperazine-1-carboxylic acid 4-iodo-pyrazol-1-yl ester, 4-Benzyl-piperazine-1-carboxylic acid 3- (4-methoxy-phenyl)-pyrazol-1-yl ester, 4-Benzyl-piperazine-1-carboxylic acid 3-(2-methoxy-phenyl)-pyrazol-1-yl ester, 4-Benzyl-piperazine-1-carboxylic acid 3-(4-nitro-phenyl)-pyrazol-1-yl ester, 4-Benzyl-piperazine-1-carboxylic acid 3- (2-fluoro-phenyl)-pyrazol-1-yl ester, 4-Benzyl-piperazine-1-carboxylic acid 3-pyridin-2-yl-pyrazol-1-yl ester, 4-Benzyl-piperazine-1-carboxylic acid 4-phenylsulfanyl-pyrazol-1-yl ester, 4-Benzyl-piperazine-1-carboxylic acid 3-thiophen-2-yl-pyrazol-1-yl ester,

4-Benzyl-piperazine-1-carboxylic acid 5-thiophen-2-yl-pyrazol-1-yl ester, 4-Benzyl-piperazine-1-carboxylic acid imidazol-1-yl ester, 4-Benzyl-piperazine-1-carboxylic acid 2-chloro-imidazol-1-yl ester, 4-Benzyl-piperazine-1-carboxylic acid 2-bromo-imidazol-1-yl ester, 4-Benzyl-piperazine-1-carboxylic acid 2-iodo-imidazol-1-yl ester, 4-Benzyl-piperazine-1-carboxylic acid 2-methyl-imidazol-1-yl ester, 4-Benzyl-piperazine-1-carboxylic acid 2-phenylsulfanyl-imidazol-1-yl ester, 4-Benzyl-piperazine-1-carboxylic acid 2-(4-methoxy-phenyl)-imidazol-1-yl ester, 4-Benzyl-piperazine-1-carboxylic acid 2- (4-fluoro-phenyl)-imidazol-1-yl ester, 4-Benzyl-piperazine-1-carboxylic acid 2-thiophen-2-yl-imidazol-1-yl ester, 4-Benzyl-piperazine-1-carboxylic acid 2-pyridin-2-yl-imidazol-1-yl ester, 4-Benzyl-piperazine-1-carboxylic acid 2, 5-dichloro-imidazol-1-yl ester, 4-Benzyl-piperazine-1-carboxylic acid 4-bromo-2, 5-dichloro-imidazol-1-yl ester, 4-Benzyl-piperazine-1-carboxylic acid 4-bromo-2-chloro-imidazol-1-yl ester, 4-Benzyl-piperazine-1-carboxylic acid 5- (4-methoxy-phenyl)-imidazol-1-yl ester, 4-Benzyl-piperazine-1-carboxylic acid 5- (4-fluoro-phenyl)-imidazol-1-yl ester, 4-Benzyl-piperazine-1-carboxylic acid 5-thiophen-2-yl-imidazol-1-yl ester, 4-Benzyl-piperazine-1-carboxylic acid 5-pyridin-2-yl-imidazol-1-yl ester, 4-Benzyl-piperazine-1-carboxylic acid 4- (5-chloro-pyridin-2-yloxy)-phenyl ester, 4-Pyridin-3-ylmethyl-piperazine-1-carboxylic acid 4- (5-chloro-pyridin-2-yloxy)-phenyl ester, 4-Pyridin-2-yl-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy) phenyl ester, 4-(1,3-Benzodioxol-5-yl)-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)- phenyl ester, 4-[2-(2-Hydroxyethoxy)ethyl]-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2- yloxy)-phenyl ester, 4-(Diphenylmethyl)piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester, 4- (4-tert-Butylbenzyl) piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy) phenyl ester, 4-(4-Fluorobenzyl)-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester, 4- (2-Thienylethyl) piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy) phenyl es- ter,

4- (1-Phenylethyl) piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy) phenyl es- ter, 4-Octylpiperazine-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy) phenyl ester, 4- (3-Dimethylamino-propyl)-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)- phenyl ester, 4-Pyrimidin-2-yl-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl es- ter, 4-Cyclopropylmethyl-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester, 4-Phenethyl-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester, 4-Pyridin-2-ylmethyl-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester, 4-Pyridin-3-ylmethyl-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester, 4-(3-Phenylpropyl)piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester, 4-(4-Phenylbutyl)piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl es- ter, 4-(3,4-Dichlorophenyl)piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy) phenyl ester, 4-(4-Fluorophenyl)piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy) phenyl ester, 4-(2-Chlorophenyl)piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy) phenyl ester, 4-Methylpiperazine-1-carboxylic acid 4-chlorophenyl ester, 4-(4-Phenylbutyl)piperazine-1-carboxylic acid 4-chlorophenyl ester, 4-[2-(2-Hydroxyethoxy) ethyl] piperazine-1-carboxylic acid 4- (4-trifluoromethylphenoxy) phenyl ester, 4- (1-Ethylpropyl) piperazine-1-carboxylic acid 4- (4-trifluoromethylphenoxy) phenyl ester, 4-Cyclohepthlpiperazine-1-carboxylic acid 4- (4-trifluoromethyl-phenoxy) phenyl ester, 4-Cyclohexylpiperazine-1-carboxylic acid 4- (4-trifluoromethyl-phenoxy) phenyl ester, 4- (4-Chlorobenzyl) piperazine-1-carboxylic acid 4- (4-trifluoromethylphenoxy) phenyl ester, 4-(4-Methylbenzyl)piperazine-1-carboxylic acid 4- (4-trifluoromethylphenoxy) phenyl ester, 4-(4-Methoxybenzyl)piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester,

4- (2-Chloro-6-fluoro-benzyl)-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)- phenyl ester, 4-(3-Methoxyphenyl)piperazine-1-carboxylic acid 4- (4-trifluoromethylphenoxy) phenyl ester, 4-Benzyl-piperazine-1-carboxylic acid 4- (3-chloro-5-trifluoromethyl-pyridin-2-yloxy) phenyl es- ter, 4-Methyl-piperazine-1-carboxylic acid pyrazol-1-yl ester, 4-Cyclopentyl-piperazine-1-carboxylic acid pyrazol-1-yl ester, 4-Phenyl-piperazine-1-carboxylic acid pyrazol-1-yl ester, 4-Pyridin-2-yl-piperazine-1-carboxylic acid pyrazol-1-yl ester, 4-Pyrimidin-2-yl-piperazine-1-carboxylic acid pyrazol-1-yl ester, 4-Benzo [1,3] dioxol-5-yl-piperazine-1-carboxylic acid pyrazol-1-yl ester, 4-Benzyl-piperazine-1-carboxylic acid 4-iodo-pyrazol-1-yl ester, 4-Cyclopentyl-piperazine-1-carboxylic acid 4-iodo-pyrazol-1-yl ester, 4- (4-Fluoro-benzyl)-piperazine-1-carboxylic acid 4-iodo-pyrazol-1-yl ester, 4-Phenyl-piperazine-1-carboxylic acid 4-iodo-pyrazol-1-yl ester, 4-Pyridin-2-yl-piperazine-1-carboxylic acid 4-iodo-pyrazol-1-yl ester, 4-Pyrimidin-2-yl-piperazine-1-carboxylic acid 4-iodo-pyrazol-1-yl ester, 4-Benzo [1,3] dioxol-5-yl-piperazine-1-carboxylic acid 4-iodo-pyrazol-1-yl ester, 4-Methyl-1, 4-diazepane-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy) phenyl ester, 4-Benzyl-1, 4-diazepane-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester, 4-(Tetrahydrofuran-2-ylmethyl)-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2- yloxy)-phenyl ester, 4-Cyclopropylmethyl-piperazine-1-carboxylic acid 4- (3-chloro-5-trifluoromethyl-pyridin-2- yloxy)-phenyl ester, 4- (Tetrahydro-furan-2-ylmethyl)-piperazine-1-carboxylic acid 4- (4-trifluoromethylphenoxy)- phenyl ester, 4-Cyclohexylmethyl-piperazine-1-carboxylic acid 4- (4-trifluoromethyl-phenoxy)-phenyl ester, 4-Cyclohexylmethyl-piperazine-1-carboxylic acid 4- (3-chloro-5-trifluoromethyl-pyridin-2- yloxy)-phenyl ester, 4-Cyclopropylmethyl-piperazine-1-carboxylic acid 4-(4-trifluoromethyl-phenoxy)-phenyl ester, 4-(Tetrahydrofuran-2-ylmethyl)-piperazine-1-carboxylic acid 4- (3-chloro-5-trifluoromethyl- pyridin-2-yloxy)-phenyl ester, 4-Naphthalen-1-ylmethyl-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)- phenyl ester, 4-(2-Cyclohexyl-ethyl)-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-

phenyl ester, 4- (3-Methoxy-phenyl)-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)- phenyl ester, 4-Cyclopropylmethyl-piperazine-1-carboxylic acid 4- [2- (4-chloro-phenyl)-ethylcarbamoyl]- phenyl ester, 4-(Tetrahydro-furan-2-ylmethyl)-piperazine-1-carboxylic acid 4- [2- (4-chloro-phenyl)- ethylcarbamoyl]-phenyl ester, 4- (3, 4-Dichloro-benzyl)-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)- phenyl ester, 4-Cyclopropylemthyl-[1,4]diazepane-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)- phenyl ester, 4-(2-Pyridin-2-yl-ethyl)-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)- phenyl ester, 4-(Pyrazin-2-yl)-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl es- ter, 4-(Benzo-isothiazol-3-yl)-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)- phenyl ester, 4-(5-Chloro-thiophen-2-ylmethyl)-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2- yloxy)-phenyl ester, <BR> <BR> <BR> 4- (3-Trifluoromethyl-phenyl)-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)- phenyl ester, 4- (5-Chloro-2-methyl-phenyl)-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2- yloxy)-phenyl ester, 4-(1-Methyl-piperidin-4-ylmethyl)-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2- yloxy)-phenyl ester, 4-Biphenyl-4-ylmethyl- [1, 4] diazepane-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)- phenyl ester 4- (5-Dimethylamino-naphthalene-1-sulfonyl)-piperazine-1-carbox ylic acid 4- (5- trifluoromethyl-pyridin-2-yloxy)-phenyl ester, 4- (3-Methoxy-benzyl)-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester, 4- (3-Fluoro-benzyl)-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester, 4-(3-Trifluoromethyl-pyridin-2-yl)-piperazine-1-carboxylic acid 4-(5-trifluoromethyl-pyridin-2- yloxy)-phenyl ester,

4- (3-Fluorobenzyl)-piperazine-1-carboxylic acid 4- (4, 6-dimethyl-pyrimidin-2-ylsulfanyl)-phenyl ester, 5- (4-Trifluoromethoxybenzyl)-2, 5-diazabicyclo [2.2. 1] heptane-2-carboxylic acid 4- (5- trifluoromethylpyridin-2-yloxy)-phenyl ester, 4-(2,4-Dimethoxyphenyl)-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)- phenyl ester, 5-Benzyl-2, 5-diazabicyclo [2.2. 1] heptane-2-carboxylic acid 4- (5-trifluoromethylpyridin-2- yloxy)-phenyl ester, 4-Pyrimidin-2-yl-piperazine-1-carboxylic acid 4- (5-chloro-pyridin-2-yloxy)-phenyl ester, 4-Cyclopropylmethyl-piperazine-1-carboxylic acid 4- (4, 4-dimethyl-2, 6-dioxo-piperidin-1-yl)- phenyl ester, 4- (4-Methoxy-benzyl)-piperazine-1-carboxylic acid 4- (4, 4-dimethyl-2, 6-dioxo-piperidin-1-yl)- phenyl ester, 4-Pyridin-3-ylmethyl-piperazine-1-carboxylic acid 4- (4, 4-dimethyl-2, 6-dioxo-piperidin-1-yl)- phenyl ester, 4-(4-Methoxy-benzyl)-piperazine-1-carboxylic acid 4- (2-cyclohexyl-acetylamino)-phenyl es- ter, 4-Cyclopropylmethyl-piperazine-1-carboxylic acid 4- (2-cyclohexyl-acetylamino)-phenyl ester, 4-Pyridin-3-ylmethyl-piperazine-1-carboxylic acid 4- (2-cyclohexyl-acetylamino)-phenyl ester, 4-Cyclopropylmethyl-piperazine-1-carboxylic acid 4- (3, 3-dimethyl-butylcarbamoyl)-phenyl ester, 4-Pyridin-3-ylmethyl-piperazine-1-carboxylic acid 4-(3,3-dimethyl-butylcarbamoyl)-phenyl es- ter, 4-(4-Methoxy-benzyl)-piperazine-1-carboxylic acid 4- (3, 3-dimethyl-butylcarbamoyl)-phenyl ester, <BR> <BR> <BR> <BR> 4- (2-Pyridin-2-yl-acetyl)-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester, Piperazine-1, 4-dicarboxylic acid tert-butyl ester 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl es- ter, Piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester hydrochloride, <BR> <BR> <BR> 4-(2-Pyridin-2-yl-acetyl)-piperazine-1-carboxylic acid 4-(5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester, and 4- (2-Pyridin-4-yl-ethyl)-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester.

Further examples of specific compounds of the invention are: Morpholine-4-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester, Morpholine-4-carboxylic acid 3- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester, Morpholine-4-carboxylic acid 4- (3, 5-dichloro-pyridin-2-yloxy)-phenyl ester, Morpholine-4-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-ylamino)-phenyl ester, Morpholine-4-carboxylic acid 4- (3, 5-dichloro-pyridin-4-yloxy)-phenyl ester, Morpholine-4-carboxylic acid 4- (4-trifluoromethyl-phenoxy)-phenyl ester, Morpholine-4-carboxylic acid 4- (2-cyano-5-trifluoromethyl-pyridine-3-yloxy)-phenyl ester, Morpholine-4-carboxylic acid 2-benzenesulfonyl-4- (3-chloro-5-trifluoromethyl-pyridine-2- yloxy)-phenyl ester, Morpholine-4-carboxylic acid 4-tert-butoxy-phenyl ester, Morpholine-4-carboxylic acid 3- (4-fluorobenzyl)-4-methyl-2-oxo-2H-chromen-7-yl ester, Morpholine-4-carboxylic acid 4-phenoxy-phenyl ester, Morpholine-4-carboxylic acid 4- (4-chlorobenzoyl)-phenyl ester, Morpholine-4-carboxylic acid 4- (3-chloro-5-trifluoromethyl)-pyridine-2-yloxy)-phenyl ester, Morpholine-4-carboxylic acid 4- [4- (4-chloro-phenyl)-thiazol-2-yl]-phenyl ester, Morpholine-4-carboxylic acid 4-pyrrol-1-yl-phenyl ester, Morpholine-4-carboxylic acid 4-imidazol-1-yl-phenyl ester, Morpholine-4-carboxylic acid 4- (3-chloro-5-trifluoromethyl)-pyridine-2-ylmethyl)-phenyl ester, Morpholine-4-carboxylic acid 4-trifluoromethylsulfanyl-phenyl ester, Morpholine-4-carboxylic acid 4-pentafluoromethyloxy-phenyl ester, Morpholine-4-carboxylic acid 4-benzyloxy-phenyl ester, Morpholine-4-carboxylic acid 4-benzyl-phenyl ester, Morpholine-4-carboxylic acid 4'-cyano-biphenyl-4-yl-ester, Morpholine-4-carboxylic acid 4'-bromo-biphenyl-4-yl-ester, Morpholine-4-carboxylic acid biphenyl-4-yl-ester, Morpholine-4-carboxylic acid 4- [3- (4-chlorophenyl)-ureido]-phenyl ester, Morpholine-4-carboxylic acid 4- (4-nitro-phenoxy)-phenyl ester, Morpholine-4-carboxylic acid 4-heptylsulfanyl-phenyl ester, Morpholine-4-carboxylic acid 4-butoxy-phenyl ester, Morpholine-4-carboxylic acid 4- (4-chloro-benzenesulfonyl)-phenyl ester, Morpholine-4-carboxylic acid 4- (4-chloromethyl-thiazol-2-yi)-phenyl ester Morpholine-4-carboxylic acid 4- (4, 4-dimethyl-2, 6-dioxo-piperidin-1-yl)-phenyl ester, cis-Morpholine-4-carboxylic acid 4- (1, 3-dioxo-octahydro-isoindol-2-yl)-phenyl ester, Morpholine-4-carboxylic acid 4- (cyclohexanecarbonyl-amino)-phenyl ester,

Morpholine-4-carboxylic acid 4- (2-cyclohexyl-acetylamino)-phenyl ester, <BR> <BR> <BR> cis/trans-Morpholine-4-carboxylic acid 4- [ (4-tert-butyl-cyclohexanecarbonyl)-amino]-phenyl ester, cis-Morpholine-4-carboxylic acid 4- [ (4-tert-butyl-cyclohexanecarbonyl)-amino]-phenyl ester, trans-Morpholine-4-carboxylic acid 4- [ (4-tert-butyl-cyclohexanecarbonyl)-amino]-phenyl es- ter, Morpholine-4-carboxylic acid 4- (3, 3-dimethyl-butyrylamino)-phenyl ester, Morpholine-4-carboxylic acid 3-benzyl-4-methyl-2-oxo-2H-chromen-7-yl ester, Morpholine-4-carboxylic acid 3- (3, 4-dichloro-benzyl)-4-methyl-2-oxo-2H-chromen-7-yi ester, <BR> <BR> <BR> Morpholine-4-carboxylic acid 3-(2-chloro-6-fluoro-benzyl)-4-methyl-2-oxo-2H-chromen-7-yl ester, Morpholine-4-carboxylic acid 3- (2, 6-dichloro-benzyl)-4-methyl-2-oxo-2H-chromen-7-yl ester, Morpholine-4-carboxylic acid 3- (2, 6-dichloro-benzyl)-6-chloro-4-methyl-2-oxo-2H-chromen-7- yl ester, Morpholine-4-carboxylic acid 6-chloro-3- (2-chloro-6-fluoro-benzyl)-4-n-propy-2-oxo-2H- chromen-7-yl ester, Morpholine-4-carboxylic acid 3- (4-methoxy-phenyl)-4-methyl-2-oxo-2H-chromen-7-yl ester, Morpholine-4-carboxylic acid 4-methyl-2-oxo-3-phenyl-2H-chromen-7-yl ester, Morpholine-4-carboxylic acid 3- (2, 5-dimethoxy-phenyl)-4-methyl-2-oxo-2H-chromen-7-yl es- ter, Morpholine-4-carboxylic acid 3- (3, 4-dimethoxy-phenyl)-4-methyl-2-oxo-2H-chromen-7-yl es- ter, Morpholine-4-carboxylic acid 4- (5, 7-bis-trifluoromethyl- [1, 8] naphthypyridin-2-yloxy)-phenyl ester, Morpholine-4-carboxylic acid 4-pyrrolidine-1-yl-phenyl ester, Morpholine-4-carboxylic acid 4-piperidine-1-yl-phenyl ester, Morpholine-4-carboxylic acid 4-morpholine-1-yl-phenyl ester, Morpholine-4-carboxylic acid 4-[(6-chloro-pyridine-3-carbonyl)-amino]-phenyl ester, Morpholine-4-carboxylic acid 4-[(6-chloro-pyridine-3-carbonyl)-amino]-phenyl ester, Morpholine-4-carboxylic acid 4-[(pyridine-2-carbonyl)-amino]-phenyl ester, 2. 6-dimethyl-morpholine-4-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester, Morpholine-4-carboxylic acid pyrazol-1-yl ester, Morpholine-4-carboxylic acid 3-bromo-pyrazol-1-yl ester, Morpholine-4-carboxylic acid 4-bromo-pyrazol-1-yl ester, Morpholine-4-carboxylic acid 5-bromo-pyrazol-1-yl ester,

Morpholine-4-carboxylic acid 3,4, 5-tribromo-pyrazol-1-yl ester, Morpholine-4-carboxylic acid 4-chloro-pyrazol-1-yl ester, Morpholine-4-carboxylic acid 4-iodo-pyrazol-1-yl ester, Morpholine-4-carboxylic acid 3- (4-methoxy-phenyl)-pyrazol-1-yl ester, Morpholine-4-carboxylic acid 3-(2-methoxy-phenyl)-pyrazol-1-yl ester, Morpholine-4-carboxylic acid 3- (4-nitro-phenyl)-pyrazol-1-yl ester, Morpholine-4-carboxylic acid 3-(2-fluoro-phenyl)-pyrazol-1-yl ester, Morpholine-4-carboxylic acid 3-pyridin-2-yl-pyrazol-1-yl ester, Morpholine-4-carboxylic acid 4-phenylsulfanyl-pyrazol-1-yl ester, Morpholine-4-carboxylic acid 3-thiophen-2-yl-pyrazol-1-yl ester, Morpholine-4-carboxylic acid 5-thiophen-2-yl-pyrazol-1-yl ester, Morpholine-4-carboxylic acid imidazol-1-yl ester, Morpholine-4-carboxylic acid 2-chloro-imidazol-1-yl ester, Morpholine-4-carboxylic acid 2-bromo-imidazol-1-yl ester, Morpholine-4-carboxylic acid 2-iodo-imidazol-1-yl ester, Morpholine-4-carboxylic acid 2-methyl-imidazol-1-yl ester, Morpholine-4-carboxylic acid 2-phenylsulfanyl-imidazol-1-yl ester, Morpholine-4-carboxylic acid 2- (4-methoxy-phenyl)-imidazol-1-yl ester, Morpholine-4-carboxylic acid 2- (4-fluoro-phenyl)-imidazol-1-yl ester, Morpholine-4-carboxylic acid 2-thiophen-2-yl-imidazol-1-yl ester, Morpholine-4-carboxylic acid 2-pyridin-2-yl-imidazol-1-yl ester Morpholine-4-carboxylic acid 2, 5-dichloro-imidazol-1-yl ester, Morpholine-4-carboxylic acid 4-bromo-2, 5-dichloro-imidazol-1-yl ester, Morpholine-4-carboxylic acid 4-bromo-2-chloro-imidazol-1-yl ester, Morpholine-4-carboxylic acid 5- (4-methoxy-phenyl)-imidazol-1-yl ester, Morpholine-4-carboxylic acid 5- (4-fluoro-phenyl)-imidazol-1-yl ester, Morpholine-4-carboxylic acid 5-thiophen-2-yl-imidazol-1-yl ester, Morpholine-4-carboxylic acid 5-pyridin-2-yl-imidazol-1-yl ester, Morpholine-4-carboxylic acid 4-trifluoromethyl-pyrimidin-2-yl ester, Morpholine-4-carboxylic acid 4-trifluoromethyl-pyrimidin-2-yl ester, Morpholine-4-carboxylic acid imidazol-1-yl ester, Morpholine-4-carboxylic acid 2-bromo-imidazol-1-yl ester, Morpholine-4-carboxylic acid 2-chloro-imidazol-1-yl ester, Morpholine-4-carboxylic acid 2-phenylsulfanyl-imidazol-1-yl ester, Morpholine-4-carboxylic acid 2- (4-methoxy-phenyl)-imidazol-1-yl ester,

Morpholine-4-carboxylic acid 4-bromo-pyrazol-1-yl ester, Morpholine-4-carboxylic acid 4-iodo-pyrazol-1-yl ester, Morpholine-4-carboxylic acid 3,4, 5-tribromo-pyrazol-1-yl ester, Morpholine-4-carboxylic acid 3- (4-methoxy-phenyl)-pyrazol-1-yl ester, Morpholine-4-carboxylic acid 3-thiophen-2-yl-pyrazol-1-yl ester, Morpholine-4-carboxylic acid pyrazol-1-yl ester, and 1-Oxo-1#4-thiomorpholine-4-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester Further examples of specific compounds of the invention are : Methyl-o-tolyl-carbamic acid 4-iodo-pyrazol-1-yl ester, Methyl-m-tolyl-carbamic acid 4-iodo-pyrazol-1-yl ester, Methyl-p-tolyl-carbamic acid 4-iodo- pyrazol-1-yl ester, (3-Chloro-phenyl)-methyl-carbamic acid 4-iodo-pyrazol-1-yl ester, (3-Fluoro- phenyl)-methyl-carbamic acid 4-iodo-pyrazol-1-yl ester, 4- (3-Trifluoromethyl-pyridin-2-yl)- piperazine-1-carboxylic acid 4-iodo-pyrazol-1-yl ester, 2, 6-Dimethyl-morpholine-4-carboxylic acid 4-iodo-pyrazol-1-yl ester, Thiomorpholine-4-carboxylic acid 4-iodo-pyrazol-1-yl ester, 3, 5-Dimethyl-morpholine-4-carboxylic acid 4-iodo-pyrazol-1-yl ester, Piperidine-1-carboxylic acid 4-iodo-pyrazol-1-yl ester, Methyl-o-tolyl-carbamic acid 2-chloro-imidazol-1-yl ester, (3-Fluoro-phenyl)-methyl-carbamic acid 2-chloro-imidazol-1-yl ester, and Methyl-phenyl-carbamic acid 5-phenylsulfanyl-pyrazol-1-yl ester.

Further examples of compounds of the invention are: N-Methyl-N-phenyl-5-hexylsulfanyl-3-p-tolyl- [1, 2,4] triazole-1-carboxamide, N-Methyl-N-phenethyl-5-ethyl-3- (4-chlorophenyl)- [1, 2,4] triazole-1-carboxamide, [3- (4-Chlorophenyl)-5-methylsulfanyl- [1, 2,4] triazol-1-yl]-morpholin-4-yl-methanone, N, N-Dimethyl-5-methylsulfanyl-3-naphthalen-2-yl- [1, 2,4] triazole-1-carboxamide, N, N-Dimethyl-3- (4-chloro-phenyl)-5-ethylsulfanyl- [1, 2,4] triazole-1-carboxamide, and N, N-Dimethyl-3-biphenyl-4-yl-5-methylsulfanyl- [1, 2,4] triazole-1-carboxamide.

The present invention also encompasses compounds of formulae I-XXXXVIII, which possess a range of pharmaceutical desirable properties.

In one embodiment, the invention is concerned with compounds of formulae I-XXXXVIII, which have a solubility in water of at least 0.5 mg/L, preferably at least 2 mg/L, more prefer-

able at least 10 mg/L, more preferable at least 50 mg/L and most preferable at least 200 mg/L as determined at 25 °C and pH 7.0.

In another embodiment, the invention is concerned with compounds of formulae I-XXXXVIII, which have a solubility in water of at least 0.5 mg/L, preferably at least 2 mg/L, more prefer- able at least 10 mg/L, more preferable at least 50 mg/L and most preferable at least 200 mg/L as determined at 25 °C and pH 2.0.

In another embodiment, the invention is concerned with compounds of formulae I-XXXXVIII, which have an IC5o value of no greater than 5 RM as determined by the assay 3190.2 or 3180.1 disclosed herein.

In another embodiment, the invention is concerned with compounds of formulae I-XXXXVIII, which have an ICgo value of less than 1 uM, preferably less than 500 nM, preferably less than 100 nM, preferably less than 50 nM, more preferable less than 25 nM, more preferable less than 10nM and even more preferable less than 5 nM as determined by the assay 3190.2 or 3180.1 disclosed herein.

In another embodiment, the invention is concerned with compounds of formulae I-XXXXVIII, which are ionized at pH 7.0.

In another embodiment, the invention is concerned with compounds of formulae I-XXXXVIII, which have a pKa in the range from 8 to 12, preferable from 9 to 12, more preferable from 10 to 12.

In another embodiment, the invention is concerned with compounds of formulae I-XXXXVIII, which have a molar weight of no greater than 1000 D.

In another embodiment, the invention is concerned with compounds of formulae I-XXXXVIII, which have a molar weight of less than 750 D, preferably less than 500 D, more preferable less than 400 D, more preferable less than 300D and even more preferably less than 250 D.

In another aspect the invention is concerned with a process for the preparation of a com- pound of formulae l-X) OCXVIII or their pharmaceutically acceptable salts, which process comprises reacting the appropriate alcohol, Rz-OH, with the appropriate carbamoylating re- agent, Lv-C (=O)-NRxRy, in a solvent according to the reaction scheme P, Basa/ solvent Rx i , H Lv N. NRY Rz +"-r Ry Rz O O and isolating the disubstituted carbamate product. In one embodiment, the invention is concerned with process Pi, wherein said carbamoylating reagent is selected from the group consisting of

In another embodiment, the invention is concerned with the process of scheme Pi, wherein said solvent is selected from the group consisting of tetrahydrofurane, dimethylformamide and N-methylpyrolidone.

In another embodiment, the invention is concerned with the process of scheme Pi, wherein said base is selected from the group consisting of triethylamine, N, N-diisopropyl-N- ethylamin and DABCO.

In another aspect the invention is concerned with a process for the preparation of a com- pound according to the general formula wherein R'is selected from C1 6-alkyl, C2 8-alkenyl and C3 10-cycloalkyl, each of which is op- tionally substituted with one or more substituents independently selected from hydroxy, sul- fanyl, oxo, halogen, amino, cyano and nitro; and R2 is selected from C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3 10- cycloalkyl, each of which is optionally substituted with one or more substituents independ- ently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6- alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3 10-cycloalkyl, wherein each of hydroxy, sul- fanyl, sulfo, amino, CI-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3 10- cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C34-heterocyclyl and C3 10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3 10-cycloalkyl is op-

tionally substituted with one or more substituents independently selected from hydroxy, sul- fanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C2 6-alkenyl, aryl, heteroaryl, C3 8-heterocyclyl and C3 10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3- 10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1 6-alkyl, C2 6-alkenyl, aryl, heteroaryl, C3 8-heterocyclyl and C3-10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1 6-alkyl, C2 6-alkenyl, perhalomethyl and perhalomethoxy ; and wherein R2 is optionally covalently bound to R'by an ether, thioether, C-C or C-N bond, to form a ring system with the N-atom to which R'and R2 are bound; and R3 is selected from hydroxy, sulfanyl, sulfo, amino, C1 6-alkyl, C2 6-alkenyl, aryl, heteroaryl, C3 8-heterocyclyl and C3-10-cycloalkyl, each of which is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl and C3-10-cycloalkyl is optionally substituted with one or more substituents inde- pendently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C, 6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3$-heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and 3-10- cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1 6-alkyl, C26-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3 10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8-heterocyclyl and C3 10-cycloalkyl is op- tionally substituted with one or more substituents independently selected from hydroxy, sul- fanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3-8- heterocyclyl and C3-10-cycloalkyl, wherein each of hydroxy, sulfanyl, sulfo, amino, C1. 8-alkyl, C2-6-alkenyl, aryl, heteroaryl, C3$-heterocyclyl and C3 10-cycloalkyl is optionally substituted with one or more substituents independently selected from hydroxy, sulfanyl, sulfo, oxo, halogen, amino, cyano, nitro, C1-6-alkyl, C2-6-alkenyl, perhalomethyl and perhalomethoxy ; and X is O or S ; or

a compound according to any one of formulae III-XXXXVIII ; or a pharmaceutically acceptable salt thereof; said process comprising the treatment of the appropriate amine, R'-NH-R2, with the appro- priate acylating reagent, Y-C (=X)-R3, in a solvent and in the presence of a base according to the reaction scheme P2 In one embodiment, the invention is concerned with the process of scheme P2, wherein Y is Cl.

In another embodiment, the invention is concerned with the process of scheme P2, wherein R3 is an aryloxy group.

In another embodiment, the invention is concerned with the process of scheme P2, wherein said solvent is selected from the group consisting of diethyl ether, tetrahydrofuran and di- chloromethane.

In another embodiment, the invention is concerned with the process of scheme P2, wherein said base is selected from the group consisting of trimethylamine, triethylamine, ethyl- diisopropyl-amine and 1, 4-diazabicyclo [2.2. 2] octane.

In another embodiment, the invention is concerned with the process of scheme P2, wherein said base is present as a functionality in one or both of the substituents R'and R2, thus form- ing a salt with the acid H-Y.

In another aspect the invention is concerned with a pharmaceutical composition comprising a compound of formulae I-XXXXVIII or a pharmaceutically acceptable salt thereof together with a pharmaceutically acceptable carrier or diluent.

In one embodiment the invention is concerned with a pharmaceutical composition, wherein said composition is in unit dosage form, comprising from about 0.05 to about 2000 mg, preferably from about 0.1 to about 500 mg and even more preferable from about 1.0 to about 100 mg of a compound of formulae l-XXXXVIII or a pharmaceutically acceptable salt thereof.

In another embodiment the invention is concerned with a pharmaceutical composition for use as a medicament for inhibiting the lipolytic activity of hormone-sensitive lipase against

triacylglycerols, diacylglycerols, cholesterol acyl esters or steroid acyl esters, said composition comprising a compound of any one of formulae I-XXXXVIII or a pharmaceutically acceptable salt thereof together with a pharmaceutically acceptable carrier or diluent.

In another embodiment the invention is concerned with a pharmaceutical composition for oral, nasal, transdermal, pulmonal, or parenteral administration.

In another aspect the invention is concerned with use of a compound according to any one of formulae I-XXXXVIII for preparation of a medicament for inhibition of the lipolytic activity of hormone-sensitive lipase against triacylglycerols, diacylglycerols, cholesterol acyl esters or steroid acyl esters.

In one embodiment the invention is concerned with said use, wherein a further antidiabetic, antiobesity, antihypertensive or appetite regulating drug is used.

In another aspect the invention is concerned with use of a compound according to any one of formulae l-XXXXVIII for the preparation of a medicament for the treatment of any disorder where it is desirable to modulate the plasma level of free fatty acids, glycerol, LDL-cholesterol, HDL-cholesterol, in- sulin and/or glucose ; and/or modulate intracellular triacylglycerol and cholesterol ester stores, intracellular level of fatty acids, fatty acid esters such as diacylglycerols, phosphatidic acids, long chain acyl-CoA's as well as citrate or malonyl-CoA ; and/or increase insulin sensitivity in adipose tissue, skeletal muscle, liver or pancreatic p cells ; and/or modulate insulin secretion from pancreatic p cells.

In one embodiment the invention is concerned with said use, wherein said disorder is se- lected from the group consisting of insulin resistance, diabetes type 1 and 2, metabolic syn- drome X, impaired glucose tolerance, hyperglycemia, dyslipidemia, obesity, abnormalities of lipoprotein metabolism and any combination thereof.

In another aspect the invention is concerned with use of a compound according to any one of formulae I-XXXXVIII or a pharmaceutical acceptable salt thereof for the preparation of a medicament.

In another aspect the invention is concerned with a method of treating a disorder of a patient where modulation of the activity of hormone-sensitive lipase is desired, the method comprising administering to said patient an effective amount of a compound according to any one of formulae I-XXXXVIII or a pharmaceutical acceptable salt thereof.

In one embodiment the invention is concerned with said method, wherein said administration is carried out by the oral, nasal, transdermal, pulmonal, or parenteral route.

In another embodiment the invention is concerned with said method, wherein said disorder is selected from the group consisting of insulin resistance, diabetes type 1 and 2, metabolic syndrome X, impaired glucose tolerance, hyperglycemia, dyslipidemia, obesity, abnormalities of lipoprotein metabolism and any combination thereof.

In another embodiment the invention is concerned with said method, wherein a further antidiabetic, antiobesity, antihypertensive or appetite regulating drug is administered to the pa- tient.

The present invention also encompasses pharmaceutically acceptable salts of the present compounds. Such salts include pharmaceutical acceptable acid addition salts, pharmaceu- tically acceptable base addition salts, pharmaceutically acceptable metal salts, ammonium and alkylated ammonium salts. Acid addition salts include salts of inorganic acids as well as organic acids. Representative examples of suitable inorganic acids include hydrochloric, hy- drobromic, hydroiodic, phosphoric, sulfuric, nitric acids and the like. Representative exam- ples of suitable organic acids include formic, acetic, trichloroacetic, trifluoroacetic, propionic, benzoic, cinnamic, citric, fumaric, glycolic, lactic, maleic, malic, malonic, mandelic, oxalic, picric, pyruvic, salicylic, succinic, methanesulfonic, ethanesulfonic, tartaric, ascorbic, pamoic, bismethylene salicylic, ethanedisulfonic, gluconic, citraconic, aspartic, stearic, palmitic, EDTA, glycolic, p-aminobenzoic, glutamic, benzenesulfonic, p-toluenesulfonic acids, sul- phates, nitrates, phosphates, perchlorates, borates, acetates, benzoates, hydroxynaphtho- ates, glycerophosphates, ketoglutarates and the like. Further examples of pharmaceutical acceptable inorganic or organic acid addition salts include the pharmaceutically acceptable salts listed in J. Pharm. Sci. 1977,66, 2, which is incorporated herein by reference. Exam- ples of metal salts include lithium, sodium, potassium, magnesium, zinc, calcium salts and the like. Examples of amines and organic amines include ammonium, methylamine, di-

methylamine, trimethylamine, ethylamine, diethylamine, propylamine, butylamine, tetrame- thylamine, ethanolamine, diethanolamine, triethanolamine, meglumine, ethylenediamine, choline, N, N'-dibenzylethylenediamine, N-benzylphenylethylamine, N-methyl-D-glucamine, guanidine and the like. Examples of cationic amino acids include lysine, arginine, histidine and the like.

The pharmaceutically acceptable salts are prepared by reacting the compound of formulae I- XXXXVIII with 1 to 4 equivalents of a base such as sodium hydroxide, sodium methoxide, sodium hydride, potassium t-butoxide, calcium hydroxide, magnesium hydroxide and the like, in solvents like ether, THF, methanol, t-butanol, dioxane, isopropanol, ethanol etc. Mixture of solvents may be used. Organic bases like lysine, arginine, diethanolamine, choline, guandine and their derivatives etc. may also be used. Alternatively, acid addition salts wherever appli- cable are prepared by treatment with acids such as hydrochloric acid, hydrobromic acid, ni- tric acid, sulfuric acid, phosphoric acid, p-toluenesulphonic acid, methanesulfonic acid, acetic acid, citric acid, maleic acid salicylic acid, hydroxynaphthoic acid, ascorbic acid, palmitic acid, succinic acid, benzoic acid, benzenesulfonic acid, tartaric acid and the like in solvents like ethyl acetate, ether, alcohols, acetone, THF, dioxane etc. Mixture of solvents may also be used.

The stereoisomers of the compounds forming part of this invention may be prepared by using reactants in their single enantiomeric form in the process wherever possible or by conducting the reaction in the presence of reagents or catalysts in their single enantiomer form or by re- solving the mixture of stereoisomers by conventional methods. Some of the preferred meth- ods include use of microbial resolution, enzymatic resolution, resolving the diastereomeric salts formed with chiral acids such as mandelic acid, camphorsulfonic acid, tartaric acid, lac- tic acid, and the like wherever applicable or chiral bases such as brucine, (R)-or (S)- phenylethylamine, cinchona alkaloid and their derivatives and the like. Commonly used methods are compiled by Jaques et al in"Enantiomers, Racemates and Resolution" (Wiley Interscience, 1981). More specifically the compound of formula I may be converted to a 1: 1 mixture of diastereomeric amides by treating with chiral amines, aminoacids, aminoalcohols derived from aminoacids; conventional reaction conditions may be employed to convert acid into an amide; the dia-stereomers may be separated either by fractional crystallization or chromatography and the stereoisomers of compound of formulae I-XXXXVIII may be pre- pared by hydrolysing the pure diastereomeric amide.

Various polymorphs of compound of general formulae I-XXXXVIII forming part of this inven- tion may be prepared by crystallization of compound of formulae I-XXXXVIII under different conditions. For example, using different solvents commonly used or their mixtures for recrys-

tallization ; crystallizations at different temperatures; various modes of cooling, ranging from very fast to very slow cooling during crystallizations. Polymorphs may also be obtained by heating or melting the compound followed by gradual or fast cooling. The presence of poly- morphs may be determined by solid probe NMR spectroscopy, IR spectroscopy, differential scanning calorimetry, powder X-ray diffraction or such other techniques.

The invention also encompasses prodrugs of the present compounds, which on administra- tion undergo chemical conversion by metabolic processes before becoming active pharma- cological substances. In general, such prodrugs will be functional derivatives of the present compounds, which are readily convertible in vivo into the required compound of the formulae I-XXXXVIII. Conventional procedures for the selection and preparation of suitable prodrug derivatives are described, for example, in"Design of Prodrugs", ed. H. Bundgaard, Elsevier, 1985.

The invention also encompasses active metabolites of the present compounds.

The invention also relates to pharmaceutical compositions comprising, as an active ingredi- ent, at least one compound of the formula I or any optical or geometric isomer or tautomeric form thereof including mixtures of these or a pharmaceutically acceptable salt thereof to- gether with one or more pharmaceutically acceptable carriers or diluents.

Furthermore, the invention relates to the use of compounds of the general formulae 1- XXXXVIII or their tautomeric forms, their stereoisomers, their polymorphs, their pharmaceuti- cally acceptable salts or pharmaceutically acceptable solvates thereof for the preparation of a pharmaceutical composition for the treatment and/or prevention of disorders where a de- creased level of plasma FFA is desirable, such as the conditions mentioned above.

In another aspect, the present invention relates to a method of treating and/or preventing type 2 diabetes, insulin resistance, metabolic syndrome X, impaired glucose tolerance, dyslipidemia and abnormalities of lipoprotein metabolism.

In a still further aspect, the present invention relates to the use of one or more compounds of the general formulae I-XXXXVIII, or pharmaceutically acceptable salts thereof, for the preparation of a pharmaceutical composition for the treatment and/or prevention of type 2 diabetes, insulin resistance, metabolic syndrome X, impaired glucose tolerance, dyslipidemia and abnormalities of lipoprotein metabolism.

In a still further aspect, the present compounds are useful for the delaying or prevention of the progression from impaired glucose tolerance to type 2 diabetes.

In a still further aspect, the present compounds are useful for the delaying or prevention of the progression from non-insulin requiring type 2 diabetes to insulin requiring type 2 diabe tes.

In another aspect, the present compounds reduce triglyceride levels and are accordingly useful for the treatment and/or prevention of ailments and disorders such as diabetes and/or obesity.

In still another aspect, the compounds of general formulae I-XXXXVIII are useful for the treatment of hyperglycemia, elevated HbAic level, hyperinsulinemia, type 1.5 diabetes, latent autoimmune diabetes in adults, maturity onset diabetes, beta-cell apoptosis, hemochromato- sis induced diabetes, impaired glucose tolerance, impaired fasting glucose, metabolic syn- drome X, insulin resistance, impaired lipid tolerance, cystic fibrosis related diabetes, polycys- tic ovarian syndrome, and gestational diabetes.

In still another aspect, the compounds of general formulae I-XXXXVIII are useful for the treatment of obesity, dyslipidemia, diabetic dyslipidemia, hyperlipidemia, hypertriglyceride- mia, hyperlipoproteinemia, hypercholesterolemia, hypertension, essential hypertension, acute hypertensive emergency, arteriosclerosis, atherosclerosis, restenosis, intermittent claudication (atherosclerosis oblitterens), cardiovascular disease, cardiomyopathy, cardiac hypertrophy, left ventricular hypertrophy, coronary artery disease, early coronary artery dis- ease, heart insufficiency, exercise tolerance, chronic heart failure, mild chronic heart failure, arrhythmia, cardiac dysrythmia, syncopy, heart attack, myocardial infarction, Q-wave myo- cardial infarction, stroke, acute coronary syndrome, angina pectoris, unstable angina, cardiac bypass reocclusion, diastolic dysfunction, systolic dysfunction, non-Q-wave cardiac necrosis, catabolic changes after surgery, acute pancreatitis, and irritable bowel syndrome In still another aspect, the compounds of general formulae I-XXXXVIII may be useful for the treatment of diabetic retinopathy, background retinopathy, preproliferative retinopathy, prolif- erative retinopathy, macular edema, cataracts, nephropathy, nephrotic syndrome, diabetic nephropathy, microalbuminuria, macroalbuminuria, neuropathy, diabetic neuropathy, distal symmetrical sensorimotor polyneuropathy, and diabetic autonomic neuropathy.

In still another aspect, the compounds of general formulae I-XXXXVIII are useful for increas- ing the number of beta-cells in a patient, increasing the size of beta-cells in a patient or stimulating beta-cell proliferation, modulating beta-cell function and insulin secretion in a pa- tient in need thereof, which method comprises administration of an effective amount of a compound of formulae I-XXXXVIII to a patient in need thereof.

The compounds of the invention are also believed to be useful for reducing body weight in a patient in need thereof.

The compounds of the invention are also believed to be useful Use for weight neutral treat- ment of above mentioned diseases.

The compounds of the invention are also believed to be useful for redistributing fat in a pa- tient in need thereof.

The compounds of the invention are also believed to be useful for redistributing central fat in a patient in need thereof.

The compounds of the invention are also believed to be useful for reducing or preventing central obesity.

The compounds of the invention are also believed to be useful for reducing postprandial se- rum lipid excursions.

The compounds of the invention are also believed to be useful for the treatment of fatty acid oxidation disorders such as MCAD.

In still another aspect, the compounds of general formulae I-XXXXVIII are believed to be useful for the treatment of a disease, condition or disorder wherein cholesterol is a precursor.

Such diseases, conditions or disorders may relate to testosterone, e. g. male contraception, excessive testosterone levels, PCOS and prostate cancer. They may also relate to cortisol or corticotropin, e. g. Cushing disease.

The compounds of the invention are also believed to be useful for the treatment of cancer.

Thus, the compounds of the general formulae I-XXXXVIII may be useful for the treatment of insulinoma (pancreatic islet cell tumors), e. g. malignant insulinomas and multiple insulino- mas, adipose cell carcinomas, e. g. lipocarconoma.

The compounds of the invention are also believed to be useful for the treatment of phaechromocytoma and other diseases with increased catecholamine incretion.

The compounds of the invention are also believed to be useful for the treatment of prostate cancer, e. g. adenocarcinoma.

In still another aspect, the compounds of general formulae I-XXXXVIII may be useful for the treatment of hepatic steatosis.

In still another aspect, the compounds of general formulae I-XXXXVIII may be useful for the treatment of cirrhosis.

In still another aspect, the compounds of general formulae I-XXXXVIII may be useful for the treatment of AIDS or an AIDS related diseases, condition or disorders

In still another aspect, the compounds of general formulae I-XXXXVIII may be useful for the treatment of lipodystrophy In still another aspect, the compounds of general formulae I-XXXXVIII may be useful for the treatment of lactic acidosis.

In yet another aspect, the compounds of the present invention are expected to be useful for the treatment of CNS diseases, conditions or disorders.

Thus, the compound of the present invention may be used for the treatment of Parkinsons disease, Alzheimer disease, ADHD (Attention Deficit Hyperactivity Disorder), feeding disor- ders such as bulimia and anorexia, depression, anxiety, cognitive memory disorders, age related cognitive decline, mild cognitive impairment and schizophrenia.

In yet another aspect, the compounds of the present invention may be useful for the treat- ment of inflammatory disorders, e. g. rheumatoid arthritis, psoriasis, systemic inflammatory response syndrome, sepsis and the like.

The present compounds may also be administered in combination with one or more further pharmacologically active substances eg. , selected from antiobesity agents, antidiabetics, an- tihypertensive agents, agents for the treatment and/or prevention of complications resulting from or associated with diabetes and agents for the treatment and/or prevention of complica- tions and disorders resulting from or associated with obesity.

Thus, in a further aspect of the invention the present compounds may be administered in combination with one or more antiobesity agents or appetite regulating agents.

Such agents may be selected from the group consisting of CART (cocaine amphetamine regulated transcript) agonists, NPY (neuropeptide Y) antagonists, MC4 (melanocortin 4) agonists, orexin antagonists, TNF (tumor necrosis factor) agonists, CRF (corticotropin releas- ing factor) agonists, CRF BP (corticotropin releasing factor binding protein) antagonists, uro- cortin agonists, p3 agonists, MSH (melanocyte-stimulating hormone) agonists, MCH (melanocyte-concentrating hormone) antagonists, CCK (cholecystokinin) agonists, serotonin re-uptake inhibitors, serotonin and noradrenaline re-uptake inhibitors, mixed serotonin and noradrenergic compounds, 5HT (serotonin) agonists, bombesin agonists, galanin antago- nists, growth hormone, growth hormone releasing compounds, TRH (thyreotropin releasing hormone) agonists, UCP 2 or 3 (uncoupling protein 2 or 3) modulators, leptin agonists, DA agonists (bromocriptin, doprexin), lipase/amylase inhibitors, RXR (retinoid X receptor) modu- lators or TR f3 agonists.

In one embodiment of the invention the antiobesity agent is leptin.

In another embodiment the antiobesity agent is dexamphetamine or amphetamine.

In another embodiment the antiobesity agent is fenfluramine or dexfenfluramine.

In still another embodiment the antiobesity agent is sibutramine.

In a further embodiment the antiobesity agent is orlistat.

In another embodiment the antiobesity agent is mazindol or phentermine.

Suitable antidiabetics comprise insulin, exendin-4, GLP-1 (glucagon like peptide-1) deriva- tives such as those disclosed in WO 98/08871 to Novo Nordisk A/S, which is incorporated herein by reference as well as orally active hypoglycaemic agents.

The orally active hypoglycaemic agents preferably comprise sulphonylureas, biguanides, meglitinides, glucosidase inhibitors, glucagon antagonists such as those disclosed in WO 99/01423 to Novo Nordisk A/S and Agouron Pharmaceuticals, Inc., GLP-1 agonists, potas- sium channel openers such as those disclosed in WO 97/26265 and WO 99/03861 to Novo Nordisk A/S which are incorporated herein by reference, DPP-IV (dipeptidyl peptidase-IV) inhibitors, inhibitors of hepatic enzymes involved in stimulation of gluconeogenesis and/or glycogenolysis, glucose uptake modulators, compounds modifying the lipid metabolism such as antihyperlipidemic agents and antilipidemic agents as HMG CoA inhibitors (statins), com- pounds lowering food intake, RXR agonists and agents acting on the ATP-dependent potas- sium channel of the (3-celles.

In one embodiment of the invention the present compounds are administered in combination with insulin.

In a further embodiment the present compounds are administered in combination with a sul- phonylurea eg. tolbutamide, glibenclamide, glipizide or glicazide.

In another embodiment the present compounds are administered in combination with a biguanide eg. metformin.

In yet another embodiment the present compounds are administered in combination with a meglitinide eg. repaglinide or senaglinide.

In a further embodiment the present compounds are administered in combination with an a-glucosidase inhibitor eg. miglitol or acarbose.

In another embodiment the present compounds are administered in combination with an agent acting on the ATP-dependent potassium channel of the ß-cells eg. tolbutamide, gliben- clamide, glipizide, glicazide or repaglinide.

Furthermore, the present compounds may be administered in combination with nateglinide.

In still another embodiment the present compounds are administered in combination with an antihyperlipidemic agent or antilipidemic agent eg. cholestyramine, colestipol, clofibrate, gemfibrozil, lovastatin, pravastatin, simvastatin, probucol or dextrothyroxine.

In a further embodiment the present compounds are administered in combination with more than one of the above-mentioned compounds eg. in combination with a sulphonylurea and metformin, a sulphonylurea and acarbose, repaglinide and metformin, insulin and a sul- phonylurea, insulin and metformin, insulin, insulin and lovastatin, etc.

Furthermore, the present compounds may be administered in combination with one or more antihypertensive agents. Examples of antihypertensive agents are (3-blockers such as alpre- nolol, atenolol, timolol, pindolol, propranolol and metoprolol, ACE (angiotensin converting en- zyme) inhibitors such as benazepril, captopril, alatriopril, enalapril, fosinopril, lisinopril, quinapril and ramipril, calcium channel blockers such as nifedipine, felodipine, nicardipine, isradipine, nimodipine, diltiazem and verapamil, and a-blockers such as doxazosin, urapidil, prazosin and terazosin. Further reference can be made to Remington: The Science and Practice of Pharmacy, 19th Edition, Gennaro, Ed. , Mack Publishing Co., Easton, PA, 1995.

It should be understood that any suitable combination of the compounds according to the in- vention with one or more of the above-mentioned compounds and optionally one or more fur- ther pharmacologically active substances are considered to be within the scope of the pre- sent invention.

The present invention also relates to processes according to reaction schemes Pi and P2 for the preparation of the above said novel compounds, their derivatives, their analogs, their tautomeric forms, their stereoisomers, their polymorphs, their pharmaceutically acceptable salts or pharmaceutically acceptable solvates.

Pharmaceutical compositions.

The compounds of the invention may be administered alone or in combination with pharma- ceutically acceptable carriers or excipients, in either single or multiple doses. The pharmaceutical compositions according to the invention may be formulated with pharmaceutically acceptable carriers or diluents as well as any other known adjuvants and excipients in accordance with conventional techniques such as those disclosed in Remington: The Science and Practice of Pharmacy, 19th Edition, Gennaro, Ed. , Mack Publishing Co. , Easton, PA, 1995. The compositions may appear in conventional forms, for example capsules, tablets, aerosols, solutions, suspensions or topical applications.

The pharmaceutical compositions may be specifically formulated for administration by any suitable route such as the oral, rectal, nasal, pulmonary, topical (including buccal and sublin- gual), transdermal, intracisternal, intraperitoneal, vaginal and parenteral (including subcuta- neous, intramuscular, intrathecal, intravenous and intradermal) route, the oral route being preferred. It will be appreciated that the preferred route will depend on the general condition and age of the subject to be treated, the nature of the condition to be treated and the active ingredient chosen.

Pharmaceutical compositions for oral administration include solid dosage forms such as cap- sules, tablets, dragees, pills, lozenges, powders and granules. Where appropriate, they can be prepared with coatings such as enteric coatings or they can be formulated so as to pro- vide controlled release of the active ingredient such as sustained or prolonged release ac- cording to methods well-known in the art.

Liquid dosage forms for oral administration include solutions, emulsions, suspensions, syr- ups and elixirs.

Pharmaceutical compositions for parenteral administration include sterile aqueous and non- aqueous injectable solutions, dispersions, suspensions or emulsions as well as sterile pow- ders to be reconstituted in sterile injectable solutions or dispersions prior to use. Depot in- jetable formulations are also contemplated as being within the scope of the present inven- tion.

Other suitable administration forms include suppositories, sprays, ointments, cremes, gels, inhalants, dermal patches, implants etc.

The therapeutic dose of the compound will depend upon the frequency and mode of administration, the sex, age, weight and general condition of the subject treated, the nature and severity of the condition treated and any concomitant diseases to be treated and other factors evident to those skilled in the art. The formulations may conveniently be presented in unit dosage form by methods known to those skilled in the art. In one embodiment the composition in unit dosage form, comprises from about 0.05 to about 2000 mg, preferably from about 0.1 to about 500 mg of the compound of formula I pharmaceutical acceptable salt thereof.

In a still further embodiment the pharmaceutical composition is for oral, nasal, transdermal, pulmonal, or parenteral administration.

For parenteral routes, such as intravenous, intrathecal, intramuscular and similar administration, typically doses are in the order of about half the dose employed for oral administration.

The compounds of this invention are generally utilized as the free substance or as a pharma- ceutically acceptable salt thereof. One example is an acid addition salt of a compound having the utility of a free base. When a compound of the invention contains a free base such salts are prepared in a conventional manner by treating a solution or suspension of a free base of the compound with a chemical equivalent of a pharmaceutically acceptable acid, for example, inor- ganic and organic acids. Representative examples are mentioned above. Physiologically ac- ceptable salts of a compound with a hydroxy group include the anion of said compound in com- bination with a suitable cation such as sodium or ammonium ion.

For parenteral administration, solutions of the present compounds in sterile aqueous solution, aqueous propylene glycol or sesame or peanut oil may be employed. Such aqueous solutions should be suitable buffered if necessary and the liquid diluent first rendered isotonic with suffi- cient saline or glucose. The aqueous solutions are particularly suitable for intravenous, intra- muscular, subcutaneous and intraperitoneal administration. The sterile aqueous media em- ployed are all readily available by standard techniques known to those skilled in the art.

Suitable pharmaceutical carriers include inert solid diluents or fillers, sterile aqueous solution and various organic solvents. Examples of suitable carriers are water, salt solutions, alcohols, polyethylene glycols, polyhydroxyethoxylated castor oil, peanut oil, olive oil, gelatine, lactose, terra alba, sucrose, cyclodextrin, amylose, magnesium stearate, talc, gelatin, agar, pectin, acacia, stearic acid or lower alkyl ethers of cellulose, silicic acid, fatty acids, fatty acid amines, fatty acid monoglycerides and diglycerides, pentaerythritol fatty acid esters, polyoxyethylene, hydroxymethylcellulose and polyvinylpyrrolidone. Similarly, the carrier or diluent may include any sustained release material known in the art, such as glyceryl monostearate or glyceryl distearate, alone or mixed with a wax. The formulations may also include wetting agents, emulsifying and suspending agents, preserving agents, sweetening agents or flavouring agents.

The pharmaceutical compositions formed by combining the compounds of the invention and the pharmaceutically acceptable carriers are then readily administered in a variety of dosage forms suitable for the disclosed routes of administration. The formulations may conveniently be pre- sented in unit dosage form by methods known in the art of pharmacy.

Formulations of the present invention suitable for oral administration may be presented as dis- crete units such as capsules or tablets, each containing a predetermined amount of the active ingredient, and which may include a suitable excipient. These formulations may be in the form of powder or granules, as a solution or suspension in an aqueous or non-aqueous liquid, or as an oil-in-water or water-in-oil liquid emulsion.

If a solid carrier is used for oral administration, the preparation may be tablette, placed in a hard gelatine capsule in powder or pellet form or it can be in the form of a troche or lozenge.

The amount of solid carrier will vary widely but will usually be from about 25 mg to about 1 g.

If a liquid carrier is used, the preparation may be in the form of a syrup, emulsion, soft gela- tine capsule or sterile injectable liquid such as an aqueous or non-aqueous liquid suspension or solution.

A typical tablet which may be prepared by conventional tabletting techniques may contain:

Core: Active compound (as free compound or salt thereof) 5 mg Colloidal silicon dioxide (Aerosil) 1.5 mg Cellulose, microcryst. (Avicel) 70 mg Modified cellulose gum (Ac-Di-Sol) 7.5 mg Magnesium stearate q. s.

Coating: HPMC approx. 9 mg *Mywacett 9-40 T approx. 0.9 mg *Acylated monoglyceride used as plasticizer for film coating.

The compounds of the invention may be administered to a patient which is a mammal, espe- cially a human in need thereof. Such mammals include also animals, both domestic animals, e. g. household pets, and non-domestic animals such as wildlife.

In a further aspect of the invention the present compounds may be administered in combination with further pharmacologically active substances e. g. an antidiabetic or other pharmacologically active material, including other compounds for the treatment and/or prevention of insulin resistance and diseases, wherein insulin resistance is the pathophysiological mechanism.

Furthermore, the compounds according to the invention may be administered in combination with antiobesity agents or appetite regulating agents.

EXAMPLES.

General Methods All reactions involving air-sensitive reagents were performed under nitrogen using syringe- septum cap techniques. The glassware were dried by heating with a heath-gun. MgS04 were used to dry solutions. Solvents were removed in vacuo by rotary evaporation. Melting points were recorded on a Buchi 535, Bruker AMX 400 and Bruker DRX 300 instruments were used to record'H NMR spectra at 400 and 300 MHz respectively with tetramethylsilane (TMS) as internal standard. Coupling constants (J) are given in Hz.

Materials Test compounds were synthesized or when commercially available they were purchased from Specs, Maybridge, Comgenex, Peakdale or Bionet. For the synthesized compounds the procedure for synthesis and measured characteristics of the compound are stated in the ex- ample. All compounds for which no synthesis procedure is stated in the examples are com- mercially available and have been purchased, or were prepared by standard methods de- scribed in the literature.

N-methyl-phenethylcarbamoyl chloride was prepared from N-methyl-phenethylamine and phosgene using triethylamine as a base in dichloromethane. 1-Methyl-3- (morpholine-4- carbonyl)-3H-imidazol-1-ium iodide, 3- (3, 4-dihydro-2H-quinoline-1-carbonyl)-1-methyl-3H- imidazol-1-ium iodide and 1-methyl-3-(methyl-phenyl-carbamoyl)-3H-imidazol-1-ium iodide was prepared as described by Batey, R. A. , Tetrahedron Lett. 39,1998, 6267.

1-Hydroxypyrazole was prepared as described in Begtrup, Vedso, J. Chem. Soc. Perkin Trans 1,1995, 243. 1-hydroxy-4-bromopyrazole was prepared as described in Balle et al., J.

Org. Chem. 64,1999, 5366. 1-hydroxy-3- (4-methoxyphenyl) pyrazole was prepared as de- scribed in Eskildsen et al., J. Org. Chem. 2001 (in press). 1-hydroxyimidazole was prepared as described in Eriksen et al., J. Org. Chem. 63,1998, 12.1-hydroxy-1, 2, 3-triazole was pre- pared as described in Uhimann et al., J. Org. Chem. 62,1997, 9177.

2-Piperidin-4-ylmethyl-1, 2,3, 4-tetrahydro-isoquinoline, cyclohexyl-methyl-piperidin-4- ylmethyl-amine, methyl-phenethyl-piperidine-4-ylmethyl-amine, ethyl-piperidin-4-ylmethyl-

piperidin-4-ylmethylamine, benzyl-methyl-piperidin-4-ylmethyl-amine, benzyl-ethyl-piperidin- 4-ylmethyl-amine, methyl-piperidin-4-ylmethyl-piperidin-3-ylmethyl-amine, 1-piperidin-4- ylmethyl-piperidin-4-ol, 2-piperidin-4-ylmethyl-2, 3-dihydro-1 H-isoindole, cyclopropylmethyl- piperidin-4-ylmethyl-amine was prepared from 4-formylpiperidine-1-carboxylic acid tert.- butyl ester prepared as described by Ting, P. C. (Bioorg, Med. Chem. Lett, 11,4, 491,2001) and an appropriate amine by a reductive amination (general procedure 19).

Benzylpiperidine-4-yl-amine, methyl-piperidin-4-yl- (2-pyridin-2-yl-ethyl)-amine, cyclohexyl- methyl-piperidin-4-yl-amine, Isopropyl-methyl-piperidin-4-yl-amine, methyl-phenethyl- piperidin-4-yl-amine, methyl-piperidin-4-yl-pyridin-3-ylmethyl-amine, was prepared from 4- oxopiperidine-1-carboxylic acid tert-butyl ester by a standard reductive amination procedure as described by Mattson R. J. (J. Org. Chem. 55,2552, 1990).

Cyclopropyl-piperidin-4-yl-pyridin-4-ylmethyl-amine was prepared from 4- (cyclopropyl-pyridin- 4-ylmethyl-amino)-piperidine-1-carboxylic acid tert-butyl ester by a classical N-deprotection reaction (HCI (g) in diethyl ether or ethanol). 4- (Cyclopropyl-pyridin-4-ylmethyl-amino)- piperidine-1-carboxylic acid tert-butyl ester was prepared from 4-cyclopropylamino- piperidine-1-carboxylic acid tert-butyl ester and pyridine-4-yl-acetaldehyde by a classical re- ductive amination procedure as described by Mattson R. J. 4-Cyclopropylamino-piperidine-1- carboxylic acid tert-butyl ester was prepared from cyclopropylamine and 4-oxopiperidine-1- carboxylic acid tert-butyl ester by a standard reductive amination procedure as described by Mattson R. J. Cyclopropyl-(2-fluoro-benzyl)-piperidin-4-yl-amine, cyclopropyl-piperidin-4-yl- pyridin-3-ylmethyl-amine, cyclopropylmethyl-piperidin-4-yl-pyridin-3-ylmethyl-amine and cyclopropylmethyl-piperidin-4-yl-pyridin-4-ylmethyl-amine was prepared by a procedure simi- lar to the one described for cyclopropyl-piperidin-4-yl-pyridin-4-ylmethyl-amine.

Chloroformates were synthesized from the appropriate phenols and phosgene or a phosgene substitute like e. g. trichloromethyl chloroformate as described in K onakahara, Ozaki, Sato, Gold, Synthesis 1993 (1) 103-106, except that the crude product was separated from the diisopropylethylamine hydrochloride by extraction with diethyl ether rather than with THF.

Non-commercial N-monosubstitued piperazines were prepared by alkylation (alkylation pro- cedure as described in e. g. Masaguer, Ravina, Tetrahedron Lett. 1996,37 (29) 5171-5174) of 1-Boc-piperazine, and subsequent removal of the Boc group under acidic conditions, e. g.

by heating in a mixture of hydrochloric acid and ethanol. N-Monosubstitued homopiprazines and N-monosubstituted 2, 5-diazabicyclo [2.2. 1] heptanes were prepared in a similar manner.

Thin layer chromatography was performed on Merck DC-Alufolien, silica gel 60 F254 and components were visualized by UV254. Flash chromatography was performed using silica gel Merck 60 size 0.04-0-063 mm and a Quad 12/25 flash system.

Preparative HPLC (Method A).

The system consists of two Gilson 322 pumps equipped with 30 ml pump heads. A Gilson 215 combined autoinjector and fraction collector performs injection and fraction collection.

Detection is performed with a Gilson Diode array detector.

Separation is performed on Waters Xterra columns 19.8 mm * 100 mm, flow rate 25 ml/min.

The most widely used gradient starts at 10 % acetonitrile in water and ends after 11 min on 100 % acetonitrile, the system is buffered by 0. 01 % TFA. In special cases the gradient is al- tered to fit the separation need.

Preparative HPLC (Method B) HPLC Purification: The following instrumentation is used: Gilson 306 Pump Gilson 806 Manometric module Gilson 811 C Dynamic mixer Gilson UVNIS-155 Gilson 202 Fraction collector The instrument is controlled by Gilson Unipoint software.

The HPLC pump is connected to two eluent reservoirs containing: A: 0. 01 % TFA in water B: 0. 01 % TFA in acetonitrile The purification is performed at room temperature by injecting an appropriate volume of the sample (preferably 2 mi) onto the column, which is eluted with a gradient of acetonitrile.

The HPLC conditions and detector settings used are as follows :

Column : Waters Xterra MS C-18 X 19 x 100 mm Gradient: 50%-60% acetonitrile linearly during 12 min at 20 ml/min Detection: 210 and 270 nm Preparative HPLC (method C) The system consists of two Gilson 322 pumps equipped with 30 ml pump heads. Gilson ma- nometric module 805. A Gilson 215 combined autoinjector and fraction collector performs injection and fraction collection. Detection is performed with a Gilson Diode array detector 170. A sample contain 25-100 mg of material dissolved in 0.5-2. 0 ml of solvent (minimum water concentration : 10%).

Separation is performed on Waters Xterra, RP18 7Jum, columns 19 mm x 150 mm, flow rate 15 ml/min (sample added with a flow rate of 5 ml/min for about 1 min). The most widely used gradient starts at 5 % acetonitrile in water and ends after 14 min on 95 % acetonitrile. This concentration is maintained for 6 min. The system is buffered with 0.05% TFA. In special cases the gradient is altered to fit the separation need. The pooled fractions are evaporated to dryness in vacuo.

HPLC-MS.

The following instrumentation was used: - Hewlett Packard series 1100 G1312A Bin Pump - Hewlett Packard series 1100 Column compartment - Hewlett Packard series 1100 G13 15A DAD diode array detector - Hewlett Packard series 1100 MSD The instrument was controlled by HP Chemstation software.

The HPLC pump was connected to two eluent reservoirs containing: A: 0. 01% TFA in water B: 0. 01 % TFA in acetonitrile The analysis was performed at 40 °C by injecting an appropriate volume of the sample (pref- erably 1 pI) onto the column, which is eluted with a gradient of acetonitrile. The HPLC conditions, detector settings and mass spectrometer settings which were used are as follows : Column Waters Xterra MS C-18 X 3 mm id Gradient 10%-100% acetonitrile linear during 7.5 min at 1. Omi/min Detection 210 nm (analogue output from DAD) MS lonisation mode API-ES, Scan 100-1000 amu step 0.1 amu

General procedure 1 The phenol (1.0 mmol) was dissolved in tetrahydrofuran (15 ml) in a glass screw cap vessel, 1, 4-diazabicyclo [2.2. 2] octane (DABCO) (2.0 mmol) was added together with the respective carbamoyl chloride (2.0 mmol) at room temperature. The reaction mixture was shaken for 16 hours and poured into ethyl acetate (20 ml) and aqueous citric acid (5%; 20 ml). The organic phase was dried and evaporated to give the crude product.

General procedure 2 The phenol (1.0 mmol) was dissolved in acetonitrile (15 mi) in a glass screw cap vessel.

Triethylamine (1.0 mmol) was added together with the respective 1-methyl-3H-imidazol-1- ium iodide (1.0 mmol) at room temperature. The reaction mixture was shaken for 16-48 hours at 80 °C, cooled to room temperature and evaporated. The evaporated reaction mix- ture was dissolved in dichloromethane (20 ml) and extracted with aqueous hydrogen chloride (0.1 M; 20 ml). The aqueous phase was extracted with dichloromethane (3 x 20 ml). The combined organic phases were dried and evaporated to give the crude product.

General procedure 3 The respective phenol (1.0 mmol), 3H-imidazol-1-ium iodide (1.0 mmol) and triethylamine (1.0 mmol) in acetonitrile (3 ml) was heated at 50 °C overnight in a closed vial. The crude product was purified by flash column chromatography (Si02, ethyl acetate/heptane) yielding the respective carbamate.

General procedure 4 Carbonyldiimidazole (3.6 mmol) was suspended in THF (10mi) and the appropriate secon- dary amine (3.0 mmol) was added. The reaction mixture was refluxed for 24 to 72 hours until no traces of amine could be detected. The reaction mixture was cooled to room temperature

and the organic phase evaporated to give the crude product of high purity. The crude product was used without further purification.

General procedure 5 The crude imidazole carboxamide (3.0 mmol) was dissolved in acetonitrile (10 mi) and methyl iodide (12 mmol.) was added at room temperature. The reaction mixture was stirred for 24 to 48 hours before the organic phase was evaporated to give the crude product, which was used without further purification.

General procedure 6 The respective 1,2, 4-(1H)-triazoles were prepared as described by Blaine (US 3308131).

The 1,2, 3- (1 H)-triazoles were carbamoylated using the following method: The respective 1,2, 4- (1 H)-triazole (2.0 mmol) was dissolved in dimethylformamide (10 ml) in a glass screw cap vessel, 1, 4-diazabicyclo [2.2. 2] octane (DABCO) (5.0 mmol) was added to- gether with the respective carbamoyl chloride (5.0 mmol) at room temperature. The reaction mixture was stirred for 16 hours, evaporated to dryness and ethyl acetate (20 ml) and aque- ous citric acid (5%; 20 mi) was added. The phases were separated and the aqueous phase extracted with ethyl acetate (20 ml). The combined organic phases were dried and evapo- rated to give the crude product. general procedure 7 The aryl chloroformate was prepared from the corresponding phenol, trichloromethyl chloro- formate and ethyidiisopropylamine in dichloromethane according to the procedure described by T. Konakahara, T. Ozaki, K. Sato and B. Gold, Synthesis, 1993 (1) 103-106, except that the crude reaction mixture was used without removal of ethyidiisopropylamine hydrochloride.

To a stirred, freshly prepared solution of the aryl chloroformate in dichloromethane (1 mmol in 3 ml) at-15 °C was added a solution of the substituted piperazine (1 mmol) in dichloro- methane (1 mL). The mixture was stirred at 0 °C for 2-6 h. The solvent was removed in va- cuo and the solid residue was triturated with diethyl ether (3 x 5 ml), then with a minute amount of water (1/2-2 ml) to remove the ethyldiisopropylamine hydrochloride, filtered and dried to give the hydrochloride of the respective piperazine-1-carboxylic acid aryl ester.

General procedure 8 To a solution of the N-hydroxyazole (1.0 mmol) and ethyldiisopropylamine (1.5 mmol) in CH2CI2 (3 mL) was added the respective carbamoyl chloride (1.5 mmol) at room temperature.

The reaction mixture was stirred for 16 hours, added CH2CI2 (20 mL) and washed with aque- ous citric acid (5%; 3x20 mL). The organic phase was separated, dried (MgS04) and evapo- rated to give the crude product.

General procedure 9 A solution of the substituted piperazine in diethyl ether is added to a stirred solution of an equimolar amount of the aryl chloroformate (prepared from the corresponding phenol by conventional methods) in the same solvent at 0 °C. After completion of the addition, the mix- ture is stirred at 0 °C for 1 hour, then for 1 more hour at room temperature. The mixture is filtered, the filter cake rinsed with diethyl ether and dried to give the hydrochloride of the re- spective piperazine-1-carboxylic acid aryl ester.

General procedure 10 A disbstituted amine (1.0 eq) and diisopropylethylamine (1.5 eq) was added to a dried reac- tion flask under nitrogen. Dichloromethane or tetrahydrofuran was added to give a 0.5 mM concentration of the amine. The appropriate aryl chloroformate (1.0 eq) (prepared from the corresponding phenol by conventional methods) was dissolved in a minimum amount of di- chloromethane or tetrahydrofuran and added drop by drop at room temperature. The reaction mixture was stirred overnight, citric acid (5%) was added, and the two phases separated.

The aqueous phase was extracted twice with dichloromethane, the combined organic phases were dried with MgS04, filtered and evaporated to give the crude product.

General procedure 11 An appropriate amine (1.0 eq. ) was dissolved in dichloromethane (0.5 mM concentration of the amine) in a dried reaction flask under nitrogen. The appropriate aryl chloroformate (1.0 eq. ) (prepared from the corresponding phenol by conventional methods) was dissolved in a minimum amount of dichloromethane and added drop by drop at room temperature. Heptane was added to give a 20% solution in dichloromethane and the crude product was isolated by filtration. The crude product was washed with a mixture of dichloromethane/heptane (5: 1) and dried in vacuum.

General procedure 12

An appropriate amine (1.0 eq. ) and diisopropylethylamine (1.0 eq. ) was dissolved in tetrahy- drofuran (0.5 mM concentration of the amine) in a dried reaction flask under nitrogen. The appropriate aryl chloroformate (1.0 eq. ) (prepared from the corresponding phenol by conven- tional methods) was dissolved in a minimum amount of tetrahydrofuran and added drop by drop at room temperature. Acetic acid was added to the reaction mixture (pH 3-5) and the reaction mixture filtered. The organic phase was evaporated and the crude product subjected to preparative HPLC.

General procedure 13 4- (Methyl-phenyl-carbamoyloxy)-benzoic acid 2, 5-dioxo-pyrrolidin-1-yl ester (1 eq. ), diisopro- pylethylamine (1.5 eq. ) was dissolved in tetrahydrofuran (50 mM of phenol). The reaction mix- ture was added to a mono or disubstituted amine. The reaction mixture was stirred at 50 °C for 16 hours. Citric acid (5%) and tert-butyl-methylether was added and the two phases sepa- rated. The organic phase was evaporated to give the crude product.

General procedure 14 The phenol (1.0 mmol) was dissolved in tetrahydrofuran (15 mi) in a glass screw cap vessel, 1, 4-diazabicyclo [2.2. 2] octane (DABCO) (2.0 mmol) was added together with the respective carbamoyl chloride (2.0 mmol) at room temperature. The reaction mixture was shaken for 16 hours. Acetic acid was added to the reaction mixture (pH 3-5) and the reaction mixture fil- tered. The organic phase was evaporated and the crude product subjected to preparative HPLC.

General procedure 15 A solution of the substituted piperazine in diethyl ether was added to a stirred solution of an equimolar amount of the aryl chloroformate in the same solvent at 0 °C. After completion of the addition, the mixture was stirred at ambient temperature for 1-2 hours. Stirring was dis- continued and as much as possible of the solvent was removed by decantation. The residue was rinsed twice with ether by stirring and subsequent decantation and finally dried on a ro- tary evaporator to give the hydrochloride of the respective piperazine-1-carboxylic acid aryl ester.

If necessary, further purification was achieved by treating the crude product with a mixture of ethyl acetate and a slight excess of sodium bicarbonate (approx. 1. 1 eqv. ) in water, extract- ing the aqueous phase twice with ethyl acetate, drying the combined extracts, filtering and evaporating to give the piperazine-1-carboxylic acid aryl ester as a free base.

General procedure 16 To a solution of the N-hydroxyazole (1.0 mmol) and ethyidiisopropylamine (1.0 mmol) in CHCI3 (1 mL) at-30 °C was added trichloromethyl chloroformiate (1.1 mmol). The solution was stirred at-30 °C for 10 min and at room temperature for 1 h. The solution was evapo- rated to dryness at room temperature and redissolved in CHCI3 (2 mL) and cooled to-30 °C before addition of the appropriate piperazine (3 mmol). The solution was allowed to warm to room temperature over 30 min and evaporated to give the crude product.

General procedure 17 To a suspention of N-methyl-N-phenyl-carbamic acid 4- (2-amino-ethyl) phenyl ester as its TFA salt (0.5 mmol) and an aryl sulfonyl chloride (0. 75 mmol) in CH2CI2 (2 mL) was added DIPEA (1.25 mmol). The reaction mixture was stirred at rt for 2-16 h, and evaporated to dry- ness and redissolved in MeCN and purified by preparative HPLC (Gilson).

General procedure 18 A solution of the substituted piperazine in diethyl ether was added to a stirred solution of an equimolar amount of the aryl chloroformate in the same solvent at 0 °C. Then an equimolar amount of diisopropylethylamine (DIPEA) in diethyl ether solution was added and the mix- ture was stirred at ambient temperature for 1-2 hours. The solvent was removed on a ro- tary evaporator and the residue was partitioned between ethyl acetate and water. The aque- ous phase was extracted twice with ethyl acetate and the combined organic phases were dried and filtered. Removal of the solvent gave the piperazine-1-carboxylic acid aryl ester.

General procedure 19 4-Formyl-piperidine-1-carboxylic acid tert-butyl ester (1.5 g, 7.03 mmol) prepared as de- scribed by Ting, P. C. was added to a dryed screw cap wessel under nitrogen. The appropri- ate amine (7.03 mmol) methanol (10 mi) and acetic acid 100 (, ul) was added and the reaction mixture was stirred for 2 h. at room temperature. Sodium cyanoborohydride (1.0 M sol. In THF, 4.7 ml) was added during 1 minute and the mixture was stirred for 16 h. at room tem- perature. The reaction mixture was evaporated to dryness and extracted with dichloro- methane (3 x 75 ml) from a 10 % aqueous sodium hydrogene carbonate solution (100 ml).

The organic phases were pooled, dryed, and evaporated to dryness to give the crude inter-

mediate, which was subjected to flash chromatography (ethyl acetate/heptane/methanole, 1: 2: zu 4: 0: 1).

A 3M solution of hydrogen chloride (50 ml) was added to the intermediate and the reaction micture was stirred for 16 h. The reaction mixture was evaporated to dryness to give the crude product, which was dryed in vacoum. The crude product was used without without fur- ther purification.

General procedure 20 The arylboronic acid (1.2 mmol), KF (3.3 mmol), Pd2 (dba) 3 (0.03 mmol) and Pd (P (t-Bu) 3) 2 (0.06 mmol) were added to a Schlenk tube under nitrogen. The Schlenk tube was evacuated and refilled with nitrogen five times. Next the aryl halide (1.0 mmol) in THF (2 mL) was ad- ded. The reaction mixture was stirred at rt for 16 h.

General procedure 21 To a suspension of methyl-phenyl-carbamic acid 4-amino-phenyl ester (0.5 mmol), (see preparation below) and an aryl sulfonyl chloride (0.75 mmol) in CH2CI2 (2 mL) was added DIPEA (1.25 mmol). The reaction mixture was stirred at rt for 2-16 h, and evaporated to dry- ness and redissolved in MeCN and purified by preparative HPLC (Gilson).

General procedure 22 A solution of 1-benzyloxy-4-iodobenzene (4.1 mmol) in dry THF (20 mL) was cooled to-78 °C. n-Butyllithium (1.57 M in hexanes, 4.1 mmol) was added during 2 min. After the mixture was stirred for another 5 min, an aryl aldehyde (4.1 mmol) was added. The mixture was al- lowed to warm to rt during 20 min and quenched with aqueous NaHCO3. Extraction with CH2C12, drying (MgS04), filtration and evaporation provided the crude diarylmethanols which were recrystallised from EtOAc-heptane. A solution of the diarylmethanol product (2 mmol), Nal (14 mmol) in dry MeCN (20 mL) was added trimethylsilyl chloride (14 mmol) and stirred at 80 °C for 19 h. The purple reaction mixture was evaporated to dryness and treated with an aqueous solution of Na2SO3. The 4-arylmethylphenols were isolated by filtration or after ex- traction with CH2CI2 and subsequent purification by flash chromatography (Quad flash 12, EtOAc-heptane).

General procedure 23 A solution of the sulfonamide (0.2 mmol), 37% aqueous formaldehyde (0.5 mL), anf TFA (2 mL) was heated in a closed vessel in a Smith Creator microwave oven for 300 s at 150 °C.

The crude product was evaporated to dryness and purified by preparative HPLC (Gilson).

General procedure 24 A suspention of the phenol (1.0 mmol), 1, 4-diazabicyclo [2.2. 2] octane (DABCO) (1.5 mmol) and 3- [4- (tert-butyl-dimethyl-silanyloxy)-piperidine-1-carbonyl]-1-me thyl-3H-imidazol-1-ium ; iodide (1.5 mmol) in CH2CI2 (1 mL) was stirred at room temperature for 16 hours. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane). The purified tert-butyidimethylsilyl ether was desilylated by stirring with a 3.2 M solution of HCI in Et20 (20 mL) for 3 h at rt.

General procedure 25 A solution of an alcohol (0.4 mmol), a phenol (0.4 mmol), diisopropylethylamin (0.44 mmol) and tributylphosphine (0.5 mmol) in THF (2 mL) was stirred under nitrogen at rt. ADDP (0.5 mmol) dissolved in THF (2 mL) was added and the reaction mixture was stirred at rt for 16 h, filtered, evaporated to dryness and redissolved in MeCN and purified by preparative HPLC (Gilson).

General procedure 26 A solution of an alcohol (0.4 mmol), a phenol/thiophenol/N-hydroxyazole/azole or imide (0.4 mmol), diisopropylethylamin (0.44 mmol) and solid supported triphenylphosphine (3 mmol/g, 1. 2 mmol) in CH2CI2 (2 mL) was stirred under nitrogen at rt. Di-tert-butylazodicarboxylate (DBAD, 1.2 mmol) dissolved in CH2C12 (1 mL) was added and the reaction mixture was stirred at rt for 16 h. TFA (0.5 mL) was added and the mixture was stirred for further 1 h at rt.

Addition of EtOAc, filtration, followed by evaporation to dryness gave a crude which was ei- ther purified by flash chromatography (Quad flash 12, EtOAc-heptane) or redissolved in MeCN and purified by preparative HPLC (Gilson).

Preparation of 1-methyl-3H-imidazol-1-ium iodides <BR> <BR> <BR> <BR> <BR> <BR> 1-Methyl-3- (7-trifluoromethyi-3, 4-dihydro-2H-quinoline-1-carbonyl)-3H-imidazol-1-ium iodide Step A: Imidazol-1-yl-(7-trifluoromethyl-3,4-dihydro-2H-quinolin-1-y l)-methanone The title product was prepared from 7- (trifluoromethyl)-1, 2,3, 4-tetrahydroquinoline, as described in the general procedure 4. Light yellow oil. HPLC-MS: m/z = 296.1 (M+1) ; Rt: 2.85 min. i (300MHz ; CDCI3) : 2.11 (qi, 2H), 2.93 (t, 2H), 3.90 (t, 2H), 7.01 (s, 2H), 7.05 (s, 1H), 7.34 (s, 1 H), 7.34 (d, 1 H), 7.77 (s, 1 H).

Step B : 1-Methyl-3-(7-trifluoromethyl-3, 4-dihydro-2H-quinoline-1-carbonyl)-3H-imidazol-1-ium iodide The title product was prepared from imidazol-1-yl- (7-trifluoromethyl-3, 4-dihydro-2H-quinolin- 1-yl)-methanone, as described in the general procedure 5. Light yellow crystals. HPLC-MS: m/z = 310.2 (M+1), Rt: 1.84 min.

#H(300MHz ; CDCI3) : 2.01 (qi, 2H), 2.94 (t, 2H), 3.83 (t, 2H), 3.92 (s, 3H), 7.52 (s, 2H), 7.76 (s, 1 H), 7.80 (s, 1 H), 7.85 (s, 1 H), 9.62 (s, 1 H).

3- (cyclohexyl-methyl-carbamoyl)-1-methyl-3H-imidazol-1-ium iodide Step A : Imidazole-1-carboxylic acid cyclohexyl-methyl-amide The title product was prepared from cyclohexyl-methyl-amine, as described in the general procedure 4. Off-white crystals. HPLC-MS: m/z = 208.1 (M+1), Rt: 1.85 min 8H (300MHz ; CDCI3) : 1.05-1. 22 (m, 1H), 1.25-1. 45 m, 2H), 1.50-1. 61 (dt, 2H), 1.63-1, 75 (d, 1H), 1.76. 1.95 (m, 4H), 3.80-3. 95 (m, 1H), 7.09 (bs, 1H), 7.21 (bs 1H), 7.87 (bs, 1H).

Step B : 3- cyclohexyl-methyl-carbamoyl)-1-methyl-3H-imidazol-1-ium iodide

The title product was prepared from imidazole-1-carboxylic acid cyclohexyl-methyl-amide, as described in the general procedure 5. Yellow crystals; HPLC-MS: m/z = 222.2 (M+1), Rt: 1.15 min.

#H (300MHz ; CDCI3) : 1.03-1. 25, (m, 1H), 1.30-1. 60 (m, 4H), 1. 62-1. 1. 78 (m, 1H), 1.82-2. 00 (t, 4H), 3.21 (s, 3H), 3.90-4. 10 (m, 1H), 4.29 (s, 3H), 7.52 (bs, 1H), 7.66 (bs, 1H), 10.37 (bs, 1H).

3-(2,6-dimethyl-morpholine-4-carbonyl)-1-methyl-3H-imidaz ol-1-ium iodide Step A: (2,6-Dimethyl-morpholin-4-yl)-imidazol-1-yl-methanone The title product was prepared from 2, 6-dimethyl-morpholine, as described in the general procedure 4. Colourless oil. PPLC-MS: m/z = 210. 10 (M+1), Rt: 0.63 min. dd (300MHz ; CDCI3) : 1.20 (s, 3H), 1.22 (s, 3H), 2.82 (dd, 2H), 3.60-3. 75 (m, 2H), 3.93 (d, 2H), 7.11 (s, 1H), 7.20 (s, 1H), 7. 87 (s, 1H).

Step B: 3-(2,6-dimethyl-morpholine-4-carbonyl)-1-methyl-3h-imidazol- 1-ium iodide The title product was prepared from, (2, 6-Dimethyl-morpholin-4-yl)-imidazol-1-yl-methanone, as described in the general procedure 5. Light yellow oil ; HPLC-MS: m/z = 224.2 (M+1), Rt: 0.40 min. bzw (300MHz ; CDCI3) : 1.23 (s, 3H), 1.25 (s, 3H), 2.90-3. 10 (m, 2H), 3.7-3. 9 (m, 2H), 3.95-4. 15 (m, 2H), 4.26 (s, 3H), 7.67 (s, 1H), 7.73 (s, 1H) 10. 05 (s, 1H).

3-(Benzyl-methyl-carbamoyl)-1-methyl-3H-imidazol-1-ium iodide Step A : Imidazole-1-carboxylic acid benzyl-methyl-amide The title product was prepared from benzyl-methyl-amine, as described in the general proce- dure 4. Light yellow crystals. HPLC-MS: m/z = 216.1 (M+1), Rt: 1.53 min. i (300MHz ; CDCI3) : 3.04 (s, 3H), 4.65 (s, 3H), 7.08 (bs, 1 H), 7.22-7. 34 (m, 3H), 7.34-7. 50 (m, 3H), 7.93 (bs, bs, 1 H).

Step B : 3-(Benzyl-methyl-carbamoyl)-1-methyl-3H-imidazol-1-ium iodide The title product was prepared from imidazole-1-carboxylic acid benzyl-methyl-amide, as de- scribed in the general procedure 5. Light yellow crystals. HPLC-MS m/z = 230.1 (M+1), Rt: 1. 23 min.

#H (300MHz ; CDCI3) : 3.25 (s, 3H), 4.2 (s, 3H), 4.76 (s, 2H), 7.27-7. 50 (m, 5H), 7.56 (bs, 1 H), 7.70 (bs, 1H), 10.29 (bs, 1 H).

3-(Phenyl-ethyl-carbamoyl)-1-methyl-3H-imidazol-1-ium iodide Step A : Imidazole-1-carboxylic acid phenyl-ethyl-amide The title product was prepared from phenyl-ethyl-amine, as described in the general proce- dure 4. Light brown oil. HPLC-MS m/z = 216. 1 (M+1), Rt: 1.75 min. i (300MHz ; CDCI3) : 1.26 (t, 3H), 3.92 (q, 2H), 6.79 (s, 1H), 6.84 (s, 1H), 7.10 (d, 2H), 7.27- 7.45 (m, 3H), 7.55 (s, 1H).

Step B: 3-(Phenyl-ethyl-carbamoyl)-1-methyl-3H-imidazol-1-ium iodide The title product was prepared from imidazole-1-carboxylic acid phenyl-ethyl-amide, as de- scribed in the general procedure 5. Light yellow crystals. HPLC-MS m/z = 230.2 (M+1), Rt: 1.16 min.

& (300MHz ; CDCI3) : 1.28 (t, 3H), 3.96 (q, 2H), 4.10 (s, 3H), 7.03 (s, 1H), 7.27 (s, 1H), 7.35- 7.60 (m, 6 H), 9.70 (s, 1H).

3-(2,3-Dihydro-indole-1-carbonyl)-1-methyl-3H-imidazol-1- ium iodide Step A : (2, 3-Dihydro-indol-1-yl)-imidazol-1-yl-methanone The title product was prepared from Indoline, as described in the general procedure 4. Pink crystals. HPLC-MS m/z = 214.1 (M+1), Rt: 1.62 min.

i (300MHz ; CDCI3) : 3.21 (t, 2H), 4.21 (t, 2H), 7.21 (dt, 1H, 7.15 (s, 1H), 7.17-7. 29 (m, 2H), 7.36 (t, 1 H), 7.40 (d, 1 H), 8.03 (bs, 1 H).

Step 8 : 3-(2,3-Dihydro-indole-1-carbonyl)-1-methyl-3H-imidazol-1-ium iodide The title product was prepared from (2, 3-dihydro-indol-1-yl)-imidazol-1-yl-methanone, as de- scribed in the general procedure 5. Light brown crystals. HPLC-MS m/z = 228.1 (M+1), Rt : 0.94 min.

#H(300MHz ; CDCl3) : 3.42 (t, 2H), 4.34 (s, 3H), 4.71 (t, 2H), 7.17-7. 36 (m, 4H), 7.78 (bs, 1H), 7.86 (d, 1H), 10.76 (bs, 1H).

3 [ (4-Chlorophenyl)-methyl-carbamoyl]-1-methyl-3H-imidazol-1-iu m iodide Step A : Imidazole-1-carboxylic acid (4-chloro-phenyl)-methyl-amide The title product was prepared from 4-chlor-N-methylaniline, as described in the general procedure 4. Light yellow crystals. HPLC-MS m/z = 236.1 g/mol (M+1), Rt: 1.91 min.

& (300MHz ; CDCI3) : 3.47 (s, 3H), 6.85 (s, 1 H), 6.87 (s, 1 H), 7.06 (d, 2H), 7.36 (d, 2H), 7.60 (s, 1H).

Step B: [(4-Chlorophenyl)-methyl-carbamoyl]-1-methyl-3H-imidazol-1-i um iodide The title product was prepared from imidazole-1-carboxylic acid (4-chloro-phenyl)-methyl- amide, as described in the general procedure 5. Orange crystals. HPLC-MS m/z = 250.1 (M+1), Rt: 1.06 min. i (300MHz ; CDCI3) : 3.55 (s, 3H), 4.12 (s, 3H), 7.16 (bs, 1H), 7.35 (t, 1H), 7. 41 (d, 1H), 7.45 (t, 1 H), 7.51 (t, 1 H), 7.53-7. 55 (m, 1 H), 9.92 (bs, 1 H).

3-(isopropyl-methyl-carbamoyl)-1-methyl-3H-imidazol-1-ium iodide Step A: Imidazole-1-carboxylic acid isopropyl-methyl-amide

The title product was prepared from isopropyl-methylamine, as described in the general pro- cedure 4. Light yellow oil. HPLC-MS m/z = 168.1 (M+1), Rt: 0.51 min.

6s (300MHz ; CDCI3) : 1.25 (s, 3H), 1.27 (s, 3H), 2.93 (s, 3H), 4.36 (Qi, 1 H), 7.08 (bs, 1 H), 7.22 (bs, 1H), 7.88 (bs, 1 H).

Step B: 3-(isopropyl-methyl-carbamoyl)-1-methyl-3H-imidazol-1-ium iodide The title product was prepared from imidazole-1-carboxylic acid isopropyl-methyl-amide, as described in the general procedure 5. Light yellow crystals. HPLC-MS m/z = 182. 2 (M+1), Rt: 0.41 min.

& (300MHz ; CDCI3) : 1.31 (s, 3H), 1.35 (s, 3H), 3.17 (s, 3H), 4.29 (s, 3H), 4.30-4. 50 (m, 2H), 7.62 bs, 1H), 7.71 (bs, 1H), 10.29 (bs, 1H).

3-(1,3-Dihydroisoindole-2-carbonyl)-1-methyl-3H-imidazol- 1-ium iodide Step A: (1,3-Dihydroisoindole-1-yl)-imidazol-1-yl-methanone The title product was prepared from isoindol, as described in the general procedure 4. Oil.

Step B : 3-(1,3-Dihydroisoindole-2-carbonyl)-1-methyl-3H-imidazol-1-i um iodide The title product was prepared from (1, 3-dihydroisoindole-1-yl)-imidazol-1-yl-methanone, as described in the general procedure 5. Crystals. i (300MHz ; CDCI3) : 3.96 (s, 3H), 4.98 (s, 2H), 5.04 (s, 2H), 7.35 (bs, 3H), 7.44 (bs, 1 H), 7.91 (s, 1 H), 8.21 (s, 1 H), 9.74 (s, 1 H).

1-Methyl-3-(piperidine-1-carbonyl)-3H-imidazol-1-ium iodide Step A : Piperidin-1-yl-imidazol-1-yl-methanone The title product was prepared from piperidine, as described in the general procedure 4. Oil.

Step B : 1-Methyl-3-(piperidine-1-carbony/)-3H-imidazol-1-ium iodide

The title product was prepared from piperidin-1-yl-imidazol-1-yl-methanone, as described in the general procedure 5. Oil.

#H(300MHz ; CDCI3) : 1.74 (s, 6H), 3.66 (bs, 4H), 4.28 (s, 3H), 7.78 (s, 1 H), 7.83 (s, 1 H), 10.07 (s, 1H).

1-Methyl-3-(2-methyl-piperidine-1-carbonyl)-3H-imidazol-1 -ium iodide Step A : (2-Methyl-piperidin-1-yl)-imidazol-1-yl-methanone The title product was prepared from 2-methyl-piperidine, as described in the general proce- dure 4. light yellow oil. HPLC-MS m/z = 194.2 (M+1), Rt: 0.92 min.

#H(300MHz ; CDCI3) : 1.33 (d, 3H) 1.45-1. 67 (m, 2H), 1.68-1. 85 (m, 4H), 3.17 (dt, 1H), 3.86 (dd, 1H), 4.35-4. 50 (m, 1H), 7.09 (s, 1H), 7.18 (s, 1H), 7.84 (s, 1H).

Step B : 1-Methyl-3-(2-methyl-piperidine-1-carbonyl)-3H-imidazol-1-iu m iodide The title product was prepared from (2-methyl-piperidin-1-yl)-imidazol-1-yl-methanone, as described in the general procedure 5. Orange solid. HPLC-MS m/z = 208.1 (M+1), Rt: 0.57min.

9H (300MHz ; CDCI3) : 1.40 (d, H), 1.60-1. 98 m, 6H), 3.45 (t, 1H), 3.90 (d, 1H), 4.30 (s, 3H), 4.45-4. 60 (m, 1 H), 7.59 (s, 1 H), 7.62 (s, 1 H), 10.06 (s, 1 H).

1-Methyl-3- (3-methyl-piperidine-1-carbonyl)-3H-imidazol-1-ium iodide Step A : (3-Methyl-piperidin-1-yl)-imidazol-1-yl-methanone The title product was prepared from 3-methyl-piperidine, as described in the general proce- dure 4. light yellow oil. HPLC-MS m/z = 194.2 (M+1), Rt: 1.15 min.

#H (300MHz ; CDCl3) : 0.94 (d, 3H), 1.05-1. 35 (m, 1 H), 1.50-2. 00 (m, 4H), 2.67 (t, 1 H), 3.01 (dt, 1H), 3.98 (t, 2H), 7.09 (s, 1H), 7.19 (s, 1H), 7.85 (s, 1H).

Step B: 1-Methyl-3-(3-methyl-piperidine-1-carbonyl)-3H-imidazol-1-iu m iodide

The title product was prepared from (3-methyl-piperidin-1-yl)-imidazol-1-yl-methanone, as described in the general procedure 5. Yellow oil. HPLC-MS m/z = 208.1 (M+1), Rt: 0.69min.

<5H (300MHz ; CDCI3) : 0.97 (d, 3H), 1.15-1. 40 (m, 1H), 1.55-2. 00 (m, 4H), 2.92 (t, 1H), 3.28 (t, 1H), 3.90-4. 15 (m, 2H), 4.28 (s, 3H), 7.60-7. 75 (m, 2H), 10.14 (s, 1H).

1-Methyl-3-(4-methyl-piperidine-1-carbonyl)-3H-imidazol-1 -ium iodide Step A: (4-Methyl-piperidin-1-yl)-imidazol-1-yl-methanone The title product was prepared from 4-methyl-piperidine, as described in the general proce- dure 4. light yellow oil. HPLC-MS m/z = 194.2 (M+1), Rt: 1.32 min.

#H (300MHz ; CDCI3) : 1.00 (d, 3H), 1.15-1. 35 (m, 2H), 1.55-1. 85 (m, 3H), 3.02 (dt, 2H), 4.08 (d, 2H), 7.08 (s, 1H), 7.19 (s, 1H), 7.85 (s, 1H).

Step 8 : 1-Methyl-3-(4-methyl-piperidine-1-carbonyl)-3H-imidazol-1-iu m iodide The title product was prepared from (4-methyl-piperidin-1-yl)-imidazol-1-yl-methanone, as described in the general procedure 5. Yellow oil. HPLC-MS m/z = 208.1 (M+1), Rt: 0.65min. i (300MHz ; CDCI3) : 1.00 (d, 3H), 1.20-1. 50 (m, 2H), 1.66-1. 90 (m, 3H), 3.32 (t, 2H), 4.13 (d, 2H), 4.28 (s, 3H), 7.58 (s, 1H), 7.64 (s, 1H), 10.15 (s, 1H).

1-Methyl-3- (4-benzyl-piperidine-1-carbonyl)-3H-imidazol-1-ium iodide Step A: (4-Benzyl-piperidin-1-yl)-imidazol-1-yl-methanone The title product was prepared from 4-methyl-piperidine, as described in the general proce- dure 4. light yellow oil. HPLC-MS m/z = 270.2 (M+1), Rt: 2.58 min. i (300MHz ; CDCI3) : 1.10-1. 50 (m, 2H), 1.65-2. 00 (m, 3H), 2.59 (d, 2H), 2.97 (dt, 2H), 4. 08 (d, 2H), 7.05-7. 40 (m, 7H), 7.84 (s, 1 H).

Step B : 1-Methyl-3- (4-benzyl-piperidine-1-carbonyl)-3H-imidazol-1-ium iodide The title product was prepared from (4-benzyl-piperidin-1-yl)-imidazol-1-yl-methanone, as described in the general procedure 5. Yellow oil. HPLC-MS m/z = 208.1 (M+1), Rt: 0.65min.

i (300MHz ; CDCI3) : 1.30-1. 50 (m, 2H), 1.75-1. 95 (m, 3H), 2.59 (d, 2H), 3.15-3. 40 (m, 2H), 4.05-4. 20 (m, 2H), 4.25 (s, 3H), 7.10-7. 35 (m, 5H), 7.45 (bs, 1H), 7.60 (bs, 1H), 10.22 (s, 1H).

1-Methyl-3- (1, 2,3, 4-tetrahydroisoquinoline-1-carbonyl)-3H-imidazol-1-ium iodide Step A : (1, 2, 3, 4-Tetrahydroisoquinoline-1-yl)-imidazol-1-yl-methanone The title product was prepared from 1,2, 3, 4-tetrahydroisoquinoline, as described in the gen- eral procedure 4. Oil.

Step B : 1-Methyl-3-(1, 2, 3, 4-tetrahydroisoquinoline-1-carbonyl)-3H-imidazol-1-ium iodide The title product was prepared from (1,2, 3, 4-tetrahydroisoquinoline-1-yl)-imidazol-1-yl- methanone, as described in the general procedure 5. Oil. i (300MHz ; CDCI3) : 2.97 (t, 2H), 3.73 (bs, 2H), 3.94 (s, 3H), 4.75 (s, 2H), 7.15-7. 35 (m,, 4H), 7.88 (d, 1 H), 8.09 (d, 1 H), 9.63 (s, 1 H).

Preparation of Phenols 1- (4-Hydroxy-phenyl)-4, 4-dimethyl-piperidine-2, 6-dione A mixture of 4-aminophenol (3.27 g, 30.0 mmol) and 3, 3-dimethylglutaric anhydride (4. 26 g, 30.0 mmol) was heated in a round bottom flask at 165 °C for 1 h, followed by heating at 180 °C for 7 h. After cooling to room temperature the solid material was dissolved in hot ethanol, activated charcoal was added and the solution was heated at reflux for 1 h. The solid mate- rial was removed by hot filtration. The solvent was evaporated and the residue was crystal- lised from water/ethanol yielding the title compound (3.51 g, 50% yield, pink solid).

'H NMR (300 MHz, DMSO-d6) : 81. 08 (s, 6H), 2.63 (s, 4H), 6.77 + 6.86 (AB-system, 4H), 9.56 (s, 1H).

cis-2- (4-Hydroxy-phenyl)-hexahydro-isoindole-1, 3-dione A mixture of 4-aminophenol (5.46 g, 50.0 mmol) and cis-1, 2-cyclohexanedicarboxylic anhy- dride (7.71 g, 50.0 mmol) was heated in a round bottom flask at 170 °C for 2 h. After cooling to room temperature the solid material was dissolved in hot ethanol (200 ml), activated char- coal was added and the solution was heated at reflux for 1 h. The solid material was re- moved by hot filtration. The solvent was partially evaporated. The solids were collected by filtration, washed quickly with a small amount of ethanol and dried in vacuo at 40 °C yielding the title compound (8.52 g, 69% yield, pink solid).

'H NMR (300 MHz, DMSO-do 1. 38 (m, 4H), 1.73 (m, 4H), 3.02 (m, 2H), 6.82 (d, 2H), 7.02 (d, 2H), 9.66 (s, 1 H, OH); HPLC-MS: m/z = 246 (M+1); Rt = 2.53 min.

Cyclohexanecarboxylic acid (4-hydroxy-phenyl)-amide To a solution of 4-aminophenol (5.00 g, 45.8 mmol) in dichloromethane (50 ml) were added cyclohexanecarbonyl chloride (6.72 g, 45.8 mmol) and pyridine (3.70 ml, 45.8 mmol), while cooling the reaction mixture in an ice bath. After the addition was completed, the cooling bath was removed and stirring was continued overnight at room temperature. Water (100 ml) was added, the organic phase was removed and the resulting solution was extracted with ethyl acetate (3 x 300 ml). The combined organic phases were washed with water (2 x 200 ml), dried, filtered and evaporated, yielding an off-white solid. The crude product was purified by flash column chromatography (SiO2, ethyl acetate/heptane (40: 60) ), yielding a mixture of two compounds, which were dissolved in THF. 6N NaOH (aq, 32 ml) was added and the mixture was stirred at room temperature for 2.5 h. The solution was acidified with concentrated hy- drochloric acid and the organic solvent was removed by evaporation. The solid material was collected by filtration, dried and recrystallised from ethyl acetate/heptane, yielding the title compound (4.20 g, 41%, off-white solid). oh NMR (300 MHz, DMSO-d6) : 81. 12-1.48 (m, 5H), 1.65 (m, 1H), 1.70-1. 82 (m, 4H), 2.27 (m, 1H), 6.66 (d, 2H), 7.36 (d, 2H), 9.10 (s, 1H), 9.50 (s, 1H) ; HPLC-MS: m/z= 220 (M+1) ; Rt = 2.69 min.

2-Cyclohexyl-N- (4-hydroxy-phenyl)-acetamide To a solution of 4-aminophenol (3.83 g, 35.1 mmol) in dichloromethane (50 ml) were added cyclohexylacetyl chloride (11.26 g, 70.1 mmol) and pyridine (5.67 ml, 70.1 mmol), while cool- ing the reaction mixture in an ice bath. After the addition was completed, the cooling bath was removed and stirring was continued overnight at room temperature. The solvent was removed and the residue was dissolved in THF (300 ml). 6N NaOH (aq, 41 ml) was added and the mixture was stirred at room temperature for 4 h. The solution was acidified with 1 N hydrochloric acid. The solvent was removed by evaporation. The solid material was collected by filtration, dried in vacuo at 40 °C and dissolved in methanol (100 ml). A solution of KOH (5.5 g) in methanol (50 ml) was added. After stirring for 1 h at room temperature water (200 mi) was added and the organic solvent was removed by evaporation. The aqueous phase was acidified with 1 N HCI. The solid material was isolated by filtration and dried in vacuo at 40 °C yielding the title compound (6.31 g, 77% yield, pink crystals).

'H NMR (200 MHz, DMSO-ds) 0. 82-1.32 (m, 5H), 1.54-1. 76 (m, 6H), 2.12 (d, 2H), 6.66 (d, 2H), 7.32 (d, 2H), 9.12 (s, 1H), 9.57 (s, 1H) ; HPLC-MS: m/z= 234 (M+1); Rt = 3.09 min. cis/trans-4-tert-Butyl-cyclohexanecarboxylic acid (4-hydroxy-phenyl)-amide To a solution of 4-aminophenol (3.08 g, 28.2 mmol) in dichloromethane (50 ml) were added cis/trans-4-tert-butyl-cyclohexanecarbonyl chloride (11.43 g, 56.4 mmol) and pyridine (4.56 ml, 56.4 mmol), while cooling the reaction mixture in an ice bath. After the addition was com- pleted, the cooling bath was removed and stirring was continued overnight at room tempera- ture. The solvent was removed by evaporation and the residue was dissolved in THF (300 ml). 6N NaOH (aq, 33 ml) was added and the mixture was stirred at room temperature over- night. The organic phase was removed by evaporation. Water (200 ml) was added and the solid material was collected by filtration, washed with water, dried in vacuo at 40 °C and dis- solved in methanol (100 ml). A solution of KOH (2.4 g) in methanol (50 mi) was added. After stirring for 2 h at room temperature water (200 mi) was added and the organic phase was removed by evaporation. The aqueous phase was acidified with 1 N HCI and extracted with

ethyl acetate (3 x 300 ml). The combined organic phases were washed with saturated so- dium bicarbonate, dried, filtered and evaporated, yielding a pink oil, which was dried in vacuo at 40 °C. The solid material was crystallised from ethyl acetate/heptane yielding the title compound (2.03 g, 26%, pink crystals). From the first aqueous extract a second portion of product was isolated by extraction with ethyl acetate (3 x 250 ml). The combined organic phases were washed with water (400 ml), saturated sodium bicarbonate (2 x 400 ml), dried, filtered and evaporated, yielding a pink thick oil. Crystallisation from ethyl acetate/heptane yielded a further amount of title compound (2.75 g, 35%).

'H NMR (300 MHz, DMSO-d6) : 80. 80 + 0.84 (2 x s, 9H), 0.98 (m, 2H), 1.23-1. 57 (m, 4H), 1.76-1. 90 (m, 2H), 2.02-2. 14 (m, 1.5H), 2.57 (m, 0. 5H), 6.65 (d, 2H), 7.34 (d x d, 2H), 9.09 (s, 1H), 9.36 + 9.50 (2 x s, 1H) ; HPLC-MS: m/z = 276 (M+1); Rt = 4.19 and 4.27 min.

N- (4-Hydroxy-phenyl)-3, 3-dimethyl-butyramide To a solution of 4-aminophenol (3.27 g, 30.0 mmol) in dichloromethane (50 ml) were added 3, 3-dimethyl-butyryl chloride (8.08 g, 60.0 mmol) and pyridine (4.85 ml, 60.0 mmol), while cooling the reaction mixture in an ice bath. After the addition was completed, the cooling bath was removed and stirring was continued overnight at room temperature. The solvent was removed by evaporation and the residue was dissolved in THF (300 ml). 6N NaOH (aq, 35 ml) was added and the mixture was stirred at room temperature overnight. The organic pha- se was removed by evaporation. Water (200 mi) was added and the solid material was collected by filtration, washed with water, dried in vacuo at 40 °C and dissolved in methanol (100 ml). A solution of KOH (3.37 g) in methanol (50 mi) was added. After stirring for 2 days at room temperature water (300 ml) was added and the organic solvent was removed by evaporation. The aqueous phase was acidified with 1 N HCI. The solids were collected by filtration and dried under vacuum at 40 °C yielding the title compound (1.97 g, 31 %, pink solid). The mother liquor was extracted with ethyl acetate (3 x 250 ml). The combined or- ganic phases were washed with saturated sodium bicarbonate (2 x 250 ml), dried in vacuo, filtered and evaporated yielding a second amount of the title compound (0.67 g, 10%). From the first aqueous extract another portion of product was isolated by extraction with ethyl ace- tate (4 x 250 ml). The combined organic phases were washed with water (400 ml), saturated sodium bicarbonate (2 x 400 ml), dried, filtered and evaporated yielding a pink thick oil. Crys-

tallisation from ethyl acetate/heptane yielded a third amount of the title compound (2.11 g, 34%).

'H NMR (300 MHz, DMSO-d6) : 8 1. 00 (s, 9H), 2.12 (s, 2H), 6.67 (d, 2H), 7.33 (d, 2H), 9.12 (s, 1 H), 9.50 (s, 1 H) ; HPLC-MS: mlz = 208 (M+1); Rt = 2.50 min.

1- (4-Hydroxy-phenyl)-4, 4-dimethyl-piperidine-2, 6-dione A mixture of 4-aminophenol (3.27 g, 30.0 mmol) and 3, 3-dimethylglutaric anhydride (4.26 g, 30.0 mmol) was heated in a round bottom flask at 165 °C for 1 h, followed by heating at 180 °C for 7 h. After cooling to room temperature the solid material was dissolved in hot ethanol, activated charcoal was added and the solution was heated at reflux for 1 h. The solid mate- rial was removed by hot filtration. The solvent was evaporated and the residue was crystal- lised (water/ethanol) yielding the title compound (3.51 g, 50%, pink solid).

'H NMR (300 MHz, DMSO-d6) : 61. 08 (s, 6H), 2.63 (s, 4H), 6.77 + 6.86 (AB-system, 4H), 9.56 (s, 1 H).

cis-2- (4-Hydroxy-phenyl)-hexahydro-isoindole-1, 3-dione A mixture of 4-aminophenol (5.46 g, 50.0 mmol) and cis-1, 2-cyclohexanedicarboxylic anhy- dride (7.71 g, 50.0 mmol) was heated in a round bottom flask at 170 °C for 2 h. After cooling to room temperature the solid material was dissolved in hot ethanol (200 ml), activated char- coal was added and the solution was heated at reflux for 1 h. The solid material was re- moved by hot filtration. The solvent was partially evaporated. The solids were collected by filtration, washed quickly with a small amount of ethanol and dried in vacuo yielding the title compound (8.52 g, 69%, pink solid).

'H NMR (300 MHz, DMSO-d6) : 61. 38 (m, 4H), 1.73 (m, 4H), 3.02 (m, 2H), 6.82 (d, 2H), 7.02 (d, 2H), 9.66 (s, 1 H, OH); HPLC-MS: m/z = 246 (M+1); Rt = 2.53 min.

Cyclohexanecarboxylic acid (4-hydroxy-phenyl)-amide To a solution of 4-aminophenol (5.00 g, 45.8 mmol) in dichloromethane (50 ml) were added cyclohexanecarbonyl chloride (6.72 g, 45.8 mmol) and pyridine (3.70 ml, 45.8 mmol), while cooling the reaction mixture in an ice bath. After the addition was completed, the cooling bath was removed and stirring was continued overnight at room temperature. Water (100 ml) was added, the dichloromethane was removed by evaporation and the resulting solution was ex- tracted with ethyl acetate (3 x 300 ml). The combined organic phases were washed with wa- ter (2 x 200 ml), dried, filtered and evaporated, yielding an off-white solid. The crude product was purified by flash column chromatography (Si02, ethyl acetate/heptane (2: 3) ), yielding a mixture of two compounds, which were dissolved in THF. 6N NaOH (aq, 32 mi) was added and the mixture was stirred at room temperature for 2.5 h. The solution was acidified with concentrated hydrochloric acid. The THF was removed by evaporation. The solid material was collected by filtration, dried in vacuo and recrystallised (ethyl acetate/heptane), yielding the title compound (4.20 g, 41 %, off-white solid).

'H NMR (300 MHz, DMSO-d6) : 8 1. 12-1.48 (m, 5H), 1.65 (m, 1H), 1.70-1. 82 (m, 4H), 2.27 (m, 1H), 6.66 (d, 2H), 7.36 (d, 2H), 9.10 (s, 1H), 9.50 (s, 1H) ; HPLC-MS: m/z= 220 (M+1); Rt = 2.69 min.

2-Cyclohexyl-N- (4-hydroxy-phenyl)-acetamide To a solution of 4-aminophenol (3.83 g, 35.1 mmol) in dichloromethane (50 ml) were added cyclohexylacetyl chloride (11.26 g, 70.1 mmol) and pyridine (5.67 ml, 70.1 mmol), while cool- ing the reaction mixture in an ice bath. After the addition was completed, the cooling bath was removed and stirring was continued overnight at room temperature. The solvent was removed by evaporation and the residue was dissolved in THF (300 ml). 6N NaOH (aq, 41 ml) was added and the mixture was stirred at room temperature for 4 h. The solution was acidified with 1 N hydrochloric acid and the organic phase was removed by evaporation. The solid material was collected by filtration, dried and dissolved in methanol (100 ml). A solution of KOH (5.5 g) in methanol (50 ml) was added. After stirring for 1 h at room temperature wa- ter (200 mi) was added and the organic solvent was removed by evaporation. The aqueous phase was acidified with 1 N HCI. The title product was isolated by filtration and dried in vacuo (6.31 g, 77%, pink crystals).

'H NMR (200 MHz, DMSO-d6) : 80. 82-1.32 (m, 5H), 1.54-1. 76 (m, 6H), 2.12 (d, 2H), 6.66 (d, 2H), 7.32 (d, 2H), 9.12 (s, 1H), 9.57 (s, 1H) ; HPLC-MS: m/z= 234 (M+1); Rt = 3.09 min.

cis/trans-4-tert-Butyl-cyclohexanecarboxylic acid (4-hydroxy-phenyl)-amide To a solution of 4-aminophenol (3.08 g, 28.2 mmol) in dichloromethane (50 ml) were added cis/trans-4-tert-butyl-cyclohexanecarbonyl chloride (11.43 g, 56.4 mmol) and pyridine (4.56 ml, 56.4 mmol), while cooling the reaction mixture in an ice bath. After the addition was com- pleted, the cooling bath was removed and stirring was continued overnight at room tempera- ture. The solvent was removed by evaporation and the residue was dissolved in THF (300 ml). 6N NaOH (aq, 33 ml) was added and the mixture was stirred at room temperature over- night. The organic phase was removed by evaporation. Water (200 ml) was added and the solid material collected by filtration, washed with water, dried and dissolved in methanol (100 ml). A solution of KOH (2.4 g) in methanol (50 ml) was added. After stirring for 2 h at room temperature water (200 ml) was added and the organic solvent was removed by evaporation.

The aqueous phase was acidified with 1 N HCI and extracted with ethyl acetate (3 x 300 ml).

The combined organic phases were dried and evaporated, yielding a pink oil, which was dried in vacuo. The solid material was crystallised from ethyl acetate/heptane yielding the title compound (2.03 g, 26%) as pink crystals. From the first aqueous extract a second por- tion of product was isolated by extraction with ethyl acetate (3 x 250 ml). The combined or- ganic layers were washed with water (400 ml), saturated sodium bicarbonate (2 x 400 ml), dried, filtered and evaporated, yielding a pink thick oil. Crystallisation from ethyl ace- tate/heptane yielded a second amount of the title compound (2.75 g, 35%).

'H NMR (300 MHz, DMSO-d6) : 0. 80 + 0.84 (2 x s, 9H), 0.98 (m, 2H), 1.23-1. 57 (m, 4H), 1.76-1. 90 (m, 2H), 2.02-2. 14 (m, 1.5H), 2.57 (m, 0.5H), 6.65 (d, 2H), 7.34 (d x d, 2H), 9.09 (s, 1H), 9.36 + 9.50 (2 x s, 1H) ; HPLC-MS: m/z = 276 (M+1); Rt = 4.19 and 4.27 min.

N- (4-Hydroxy-phenyl)-3, 3-dimethyl-butyramide

To a solution of 4-aminophenol (3.27 g, 30.0 mmol) in dichloromethane (50 ml) were added 3, 3-dimethyl-butyryl chloride (8.08 g, 60.0 mmol) and pyridine (4.85 mi, 60.0 mmol), while cooling the reaction mixture in an ice bath. After the addition was completed, the cooling bath was removed and stirring was continued overnight at room temperature. The solvent was removed by evaporation and the residue was dissolved in THF (300 ml). 6N NaOH (aq, 35 ml) was added, the mixture was stirred at room temperature overnight and the solvent was removed by evaporation. Water (200 ml) was added and the solid material is collected by filtration, washed with water, dried in vacuo at 40 °C and dissolved in methanol (100 ml). A solution of KOH (3.37 g) in methanol (50 ml) was added. After stirring for 2 days at room temperature water (300 ml) was added, the organic solvent was removed and the aqueous phase was acidified with 1 N HCI. The solids were collected and dried yielding the title com- pound (1.97 g, 31 % yield, pink solid). The mother liquor was extracted with ethyl acetate (3 x 250 ml). The combined organic phases were washed with saturated sodium bicarbonate (2 x 250 ml), dried over sodium sulphate, filtered and evaporated yielding a second amount of the title compound (0.67 g, 10%). From the first aqueous extract another portion of product was isolated by extraction with ethyl acetate (4 x 250 ml). The combined organic phases were washed with water (400 ml), dried, filtered and evaporated yielding a pink thick oil. Crystalli- sation from ethyl acetate/heptane yielded a third amount of the title compound (2.11 g, 34%).

'H NMR (300 MHz, DMSO-d6) : 8 1. 00 (s, 9H), 2.12 (s, 2H), 6.67 (d, 2H), 7.33 (d, 2H), 9.12 (s, 1 H), 9.50 (s, 1 H) ; HPLC-MS: m/z = 208 (M+1); Rt = 2.50 min.

4- (3-Trifluoromethyl-phenoxy)-phenol Hydroquinone monobenzylether (1 g, 5.0 mmol), 3- (trifluoromethyl)-phenyl boronic acid (1.9 g, 10.0 mmol), copper (II) acetate (0.91 g, 5.0 mmol) and triethylamine (2.53 g, 25.0 mmol) were dissolved/suspended in dichloromethane (50 ml). The reaction mixture was stirred for 70 h. at room temperature and evaporated to dryness. The crude intermediate was subjected to flash chromatography (ethyl acetate/heptane (1: 4) ) (42%) and hydrogenated (10% Pd/C) using ethanol as a solvent. The organic phase was evaporated and aqueous sodium hydrox- ide (1 N, 30 ml) was added together with dichloromethane. The two phases were separated and the aqueous phase extracted with dichloromethane (30 ml x 2). The aqueous phase was acidified with aqueous hydrochloric acid (2N) and extracted with dichloromethane (30 ml x 5).

The organic phase was dried and evaporated to give the crude product (47%). HPLC-MS m/z = 254.9 (M+1), Rt: 4.39 min.

i (300MHz ; CDCI3) : 6.85 (dt, 2H), 6.94 (dt, 2H), 7.10 (dd, 1H), 7.16 (bs, 1H), 7.24-7. 30 (m, 1H), 7.39 (t, 1H).

4-Hydroxy-benzoic acid 2, 5-dioxo-pyrrolidin-1-yl ester 4-Hydroxybenzoic acid (30 g, 0.217 mmol) and 4-hydroxysuccinamide (25.32 g, 0, 220mmol) were dissolved in 1.4-dioxane (550 ml) at room temperature. After 20 min. the clear solution was cooled to 15°C and dicyclohexylcarbodiimide (44.82 ml, 0.217 mmol) was added. The reaction mixture was stirred for 18 hours and filtered. The organic phase was evaporated to dryness (86 g). Ethanol (250 ml) was added to the crude product and the mixture heated to reflux. The crude product was crystallized from ethanol/water (5: 1) (22 g, 43%), and the mother liquor recrystallized from ethanol/water (25 g, 49%). HPLC-MS: m/z = (M+1); Rt : min.

N- (6-Methoxy-pyridin-3-yl)-benzamide A solution of 5-amino-2-methoxypyridine (2.48 g, 20.0 mmol) and N ethyldiisopropylamine (2.84 g, 22.0 mmol) in dichloromethane (20 ml) was cooled in an ice-bath. Benzoyl chloride (3.09 g, 22 mmol) was slowly added by means of a syringe. The cooling bath was removed and stirring was continued at room temperature for 18 hours. Dichloromethane was added and the solution was extracted with water. The organic layer was dried over sodium sulphate, filtered and evaporated in vacuo leaving a dark solid. Crystallisation from ethyl ace- tate: heptane yielded the title compound (3.44 g, 75% yield).

'H NMR (300MHz, CDCI3) : 63. 93 (s, 3H), 6.77 (d, 1H), 7.44-7. 59 (m, 3H), 7.81 (br. s, 1H), 7.87 (d, 2H), 8. 01 (dd, 1 H), 8.16 (d, 1 H) ; HPLC-MS (Method A): m/z = 229 (M+H); Rt = 2.52 min.

Cyclohexanecarboxylic acid (6-methoxy-pyridin-3-yl)-amide hydrochloride 5-Amino-2-methoxypyride (3.72 g, 30.0 mmol), dissolved in a small amount of tetrahydrofu- ran, was added slowly to a solution of cyclohexanecarbonyl chloride (4.40 g, 30.0 mmol) in tetrahydrofuran (25 ml). After standing for 0.5 hours diethyl ether (250 ml) was added and the solids were collected by suction yielding the title compound (8. 12 g, 100% yield) as a purple solid.

'H NMR (300MHz, CDCl3) : #1. 11-1.48 (m, 5H), 1.63 (m, 1 H), 1.68-1. 83 (m, 4H), 2.32 (m, 1H), 3.81 (s, 3H), 6.80 (d, 1H), 7.92 (dd, 1H), 8.00 (br. s, 1H), 8.38 (d, 1 H), 9.92 (s, 1H) ; HPLC-MS (Method A): m/z = 235 (M+H); Rt = 2.89 min.

6'-Methoxy-4, 4-dimethyl-4, 5-dihydro-3H- [1, 3'] bipyridinyl-2, 6-dione A mixture of 5-amino-2-methoxypyride (3.72 g, 30.0 mmol) and 3, 3-dimethylglutaric anhy- dride (4.26 g, 30.0 mmol) was heated at 175 °C for 7 hours. After cooling down to room tem- perature the solid material was dissolved in a small amount of dichloromethane and purified by flash column chromatography (SiO2, ethyl acetate: heptane (40: 60) ) yielding the title com- pound (2.56 g, 34% yield) as a white solid.

'H NMR (300MHz, CDCI3) : 81. 20 (s, 6H), 2.69 (s, 4H), 3.95 (s, 3H), 3.81 (d, 1H), 7.28 (dd, 1 H), 7.89 (d, 1 H) ; HPLC-MS (Method A): m/z = 249 (M+H); Rt = 2.43 min.

N-(6-Methoxy-pyridin-3-yl)-2, 2-dimethyl-propionamide hydrochloride 5-Amino-2-methoxypyride (3.72 g, 30.0 mmol), dissolved in a small amount of tetrahydrofu- ran, was added slowly to a solution of 2, 2-dimethylpropionyl chloride (3.62 g, 30.0 mmol) in tetrahydrofuran (25 ml). After standing for 0.5 hours diethyl ether (250 mi) was added and a thick oil precipitated. The solvent was decanted and the residue was dried under reduced pressure yielding the title compound (5.50 g, 75% yield) as a purple foam.

'H NMR (300MHz, CDCI3) : 81. 22 (s, 9H), 3.83 (s, 3H), 6.86 (d, 1H), 8.00 (dd, 1H), 8.42 (d, 1 H), 9.41 (s, 1 H), 9.54 (br. s, 1 H) ; HPLC-MS (Method A): m/z = 209 (M+H); Rt = 2.28 min.

2-Cyclohexyl-N- (6-methoxy-pyridin-3-yl)-acetamide hydrochloride 5-Amino-2-methoxypyride (3.72 g, 30.0 mmol), dissolved in a small amount of tetrahydrofu- ran, was added slowly to a solution of cyclohexylacetyl chloride (4.82 g, 30.0 mmol) in tetra- hydrofuran (25 ml). After standing for 0.5 hours diethyl ether (250 ml) was added and the sol- ids were collected by suction yielding the title compound (8. 54 g, 100% yield) as a purple solid.

'H NMR (300MHz, DMSO-d6) : 60. 88-1. 04 (m, H), 1.09-1. 32 (m, 3H), 1.54-1. 82 (m, 6H), 2.18 (d, 2H), 3. 84 (s, 3H), 6.85 (d, 1H), 7.98 (dd, 1H), 8.41 (d, 1H), 9.81 (br. s, 1H), 10.10 (s, 1H) ; HPLC-MS (Method A): m/z = 249 (M+H); Rt = 3.32 min.

N-(6-Hydroxy-pyridin-3-yl)-benzamide N- (6-Methoxy-pyridin-3-yl)-benzamide (2.38 g, 10.4 mmol) was dissolved in a mixture of tet- rahydrofuran and diethyl ether. HCI-gas was bubbled into the solution for 5 minutes. More diethyl ether was added and the white precipitate was collected by suction, washed twice with diethyl ether and heated in a kugelrohr apparatus at 180 °C for 0.5 hours. The solid ma- terial was crystallised from methanol : water, washed twice with water and dried overnight in a vacuum oven, yielding the title compound (1.19 g, 53% yield) as a grey solid.

'H NMR (300MHz, CDCI3) : 8 6. 39 (d, 1H), 7.47-7. 61 (m, 3H), 7.18 (dd, 1H), 7.91 (d, 2H), 7.96 (d, 1 H) ; HPLC-MS (Method A): m/z = 215 (M+H); Rt = 1.52 min.

Cyclohexanecarboxylic acid (6-hydroxy-pyridin-3-yl)-amide Cyclohexanecarboxylic acid (6-methoxy-pyridin-3-yl)-amide hydrochloride (8. 12 g, 30.0 mmol) was heated in a kugelrohr apparatus at 190 °C for 25 minutes. After cooling to room temperature the solid material was crystallised from methanol : water, washed twice with wa- ter and dried overnight in a vacuum oven, yielding the title compound (3.09 g, 47% yield) as a purple solid.

'H NMR (300MHz, CDCI3) : 81. 09-1.46 (m, 5H), 1.63 (m, 1H), 1.68-1. 80 (m, 4H), 2.23 (m, 1 H), 6.33 (d, 1 H), 7.44 (dd, 1 H), 7.87 (d, 1 H), 9.54 (s, 1 H), 11.29 (br. s, 1 H) ; HPLC-MS (Method A): m/z = 221 (M+H); Rt = 1.84 min.

6'-Hydroxy-4, 4-dimethyl-4, 5-dihydro-3H- [1, 3'] bipyridinyl-2, 6-dione 6'-Methoxy-4, 4-dimethyl-4, 5-dihydro-3H- [1, 3'] bipyridinyl-2, 6-dione (2.56 g, 10.3 mmol) was dissolved in a mixture of tetrahydrofuran and diethyl ether. HCI-gas was bubbled into the so- lution for 5 minutes. More diethyl ether was added and the white precipitate was collected by suction, washed twice with diethyl ether and heated in a kugelrohr apparatus at 190 °C for 15 minutes yielding the title compound (2.16 g, 89% yield) as a white solid.

'H NMR (300MHz, CDC13) : 61. 08 (s, 6H), 2.52 (s, 4H), 6.34 (d, 1H), 7.19 (dd, 1H), 7.31 (d, 1 H), 11.42 (br. s, 1 H) ; HPLC-MS (Method A): m/z = 235 (M+H); Rt = 1.32 min.

N- (6-Hydroxy-pyridin-3-yl)-2, 2-dimethyl-propionamide

Under a stream of nitrogen gas N-(6-methoxy-pyridin-3-yl)-2, 2-dimethyl-propionamide hydro- chloride (5.50 g, 22.5 mmol) was heated in a round bottom flask at 180 °C for 15 minutes.

After cooling to room temperature the solid material was crystallised from a methanol-water mixture, yielding the title compound (1.13 g, 26% yield) as a dark grey solid.

'H NMR (300MHz, CDCI3) : 61. 18 (s, 9H), 6.32 (d, 1H), 7.53 (dd, 1H), 7.76 (d, 1H), 8.97 (br. s, 1 H), 11.30 (br. s, 1H) ; HPLC-MS (Method A): mlz = 195 (M+H); Rt = 1.15 min.

2-Cyclohexyl-N-(6-hydroxy-pyridin-3-yl)-acetamide 2-Cyclohexyl-N- (6-methoxy-pyridin-3-yl)-acetamide hydrochloride (8.54 g, 30.0 mmol) was heated in a kugelrohr apparatus at 160 °C for 0.5 hours. After cooling to room temperature the solid material was crystallised from a methanol-water mixture, washed twice with water and dried overnight in a vacuum oven, yielding the title compound (4.53 g, 64% yield) as a grey solid.

'H NMR (300MHz, CDCI3) : 5 0. 90-1.38 (m, 5H), 1.60-1. 92 (m, 6H), 2.17 (d, 2H), 6.50 (d, 1H), 7.50 (dd, 1 H), 7.97 (d, 1 H), 8.80 (br. s, 1 H), 11.81 (br. s, 1 H) ; HPLC-MS (Method A): m/z = 235 (M+H); Rt = 2.29 min.

3-Dimethylamino-2- (4-methoxy-phenoxy)-propenal Phosphorus oxychloride (18.4 g, 120 mmol) was added to dimethylformamide (8.8 g, 120 mmol), maintaining the temperature below 25 °C by an external ice-bath. Upon completion of the addition the reaction mixture was heated to 50 °C for 45 minutes and then cooled to room temperature. Chloroform (35 ml) was added and the resulting solution was brought to reflux.

4-Methoxyphenoxyacetaldehyde diethylacetal (9.61 g, 40.0 mmol) was added in portions.

After heating for 3 hours at reflux the solution was cooled to room temperature and poured carefully onto a solution of potassium carbonate (115 g) in water (100 ml). The mixture was cooled in an ice-bath to around room temperature and extracted twice with dichloromethane.

The combined organic layers were dried over sodium sulphate, filtered and evaporated in vacuo yielding a brown oil. The residue was heated with ethyl acetate: heptane and decanted, leaving a brown oil. The solvent was removed in vacuo to give a brown oil, which was puri- fied by flash column chromatography (Si02, ethyl acetate) yielding the title compound (3.87 g, 44% yield) as a white solid.

'H NMR (300MHz, CDC13) : 63. 00 (s, 6H), 3.75 (s, 3H), 6.54 (s, 1H), 7.80 + 7.87 (AB-system, 4H), 8.80 (s, 1 H) ; HPLC-MS (Method A): m/z = 222 (M+H); Rt = 1.73 min.

2- (3, 4-Dichloro-phenoxy)-3-dimethylamino-propenal Phosphorus oxychloride (18.4 g, 120 mmol) was added to dimethylformamide (8.8 g, 120 mmol), maintaining the temperature below 25 °C by an external ice-bath. Upon completion of the addition the reaction mixture was heated to 50 °C for 45 minutes and then cooled to room temperature. Chloroform (35 ml) was added and the resulting solution was brought to reflux.

3, 4-Dichlorophenoxyacetaldehyde diethylacetal (9.61 g, 40.0 mmol) was added in portions.

After heating for 3 hours at reflux the solution was cooled to room temperature and poured carefully onto a solution of potassium carbonate (115 g) in water (100 ml). The mixture was cooled in an ice-bath to around room temperature and extracted twice with dichloromethane.

The combined organic layers were dried over sodium sulphate, filtered and evaporated in vacuo yielding a brown oil, which was purified by flash column chromatography (Si02, ethyl acetate) yielding the title compound (5.38 g, 52% yield) as a brown solid.

'H NMR (300MHz, CDCI3) : 63. 10 (s, 6H), 6. 58 (s, 1H), 6. 82 (dd, 1H), 7.03 (d, 1H), 7.30 (d, 1H), 8. 80 (s, 1H) ; HPLC-MS (Method A): m/z= 260 (M+H); Rt = 3.14 min.

5- (4-Methoxy-phenoxy)-pyrimidin-2-ol A solution of sodium ethoxide, prepared from sodium (0.80 g, 35.0 mmol), 3-dimethylamino- 2- (4-methoxy-phenoxy)-propenal (3.87 g, 17.5 mmol) and urea (2.10 g, 35.0 mmol) in etha- nol (25 ml) was heated at reflux for 4 hours. Water (1 ml) was added and heating was con- tinued for an additional 2 hours. The solution was cooled to room temperature and neutral- ised with glacial acetic acid. Most of the solvent was removed by evaporation in vacuo. Wa- ter was added and the precipitate was isolated by suction, followed by drying in a vacuum oven, yielding the title compound (0.80 g, 21 % yield) as a yellow solid.

'H NMR (300MHz, CDCI3) : 53. 80 (s, 3H), 6.85-7. 95 (AB-system, 4H), 8.12 (s, 2H); HPLC- MS (Method A): m/z = 219 (M+H); Rt = 1.77 min.

5- (3, 4-Dichloro-phenoxy)-pyrimidin-2-ol A solution of sodium ethoxide, prepared from sodium (0.95 g, 41.4 mmol), 2- (3, 4-dichloro- phenoxy)-3-dimethylamino-propenal (5.38 g, 20.7 mmol) and urea (2.48 g, 41.4 mmol) in ethanol (25 ml) was heated at 60 °C for 4 hours. Water (1 ml) was added and heating was continued for an additional 2 hours. The solution was cooled to room temperature and neu-

tralised with glacial acetic acid. Most of the solvent was removed by evaporation in vacuo.

Water was added and the precipitate was isolated by suction, followed by drying in a vacuum oven, yielding the title compound (0.92 g, 17% yield) as a brown solid.

'H NMR (300MHz, DMSO-d6) : 87. 08 (dd, 1H), 7.38 (d, 1H), 7.59 (d, 1H), 8.35 (s, 2H), 12.06 (br. s, 1 H) ; HPLC-MS (Method A): m/z = 257 (M+H); Rt = 2.75 min.

5- (2-Nitro-phenyl)-pyrimidin-2-ol A solution of 3- (dimethylamino)-2- (2-nitrophenyl) acrylaldehyde (2.00 g, 9.08 mmol), urea (0.60 g, 9.99 mmol) and concentrated hydrochloric acid (0.50 mi) in ethanol (25 mi) was heated at 60 °C for 18 hours under a nitrogen atmosphere. An additional aliquot of concen- trated hydrochloric acid (0.50 ml) was added followed by heating at 70 °C for 24 hours. The solvent was removed by evaporation under reduced pressure. The residue was crystallised from methanol yielding the title compound (0.35 g, 18% yield) as a yellow solid.

'H NMR (300MHz, DMSO-d6) : 67. 54 (dd, 1H), 7.62 (dt, 1H), 7.76 (dt, 1H), 8.06 (dd, 1H), 8.29 (s, 2H); HPLC-MS (Method A): m/z = 218 (M+H); Rt = 1.26 min.

N-(6-Hydroxy-pyridin-3-yl)-3, 3-dimethyl-butyramide 3, 3-Dimethylbutyroyl chloride (4.04 g, 30.0 mmol) was added dropwise to a stirred solution of 5-amino-2-methoxypyridine (3.72 g, 30.0 mmol) in tetrahydrofuran (25 mL). After stirring for 1 hour at room temperature, diethyl ether was added and the solid material was isolated by suction. The N- (6-methoxy-pyridin-3-yl)-3, 3-dimethyl-butyramide hydrochloride (4.13 g, 15.96 mmol) was heated at 180 °C for 15 minutes. After cooling to room temperature the product was dissolved in methanol. Partial evaporation of the solvent yielded the title compound (1.15 g, 35% yield) as a solid.

'H NMR (300MHz, DMSO-d6) : = 1.00 (s, 9H), 2.12 (s, 2H), 6.38 (d, 1H), 7.44 (dd, 1H), 7.89 (d, 1 H), 9.59 (s, 1 H), 11.42 (br. s, 1 H); HPLC-MS (Method A): m/z = 209 (M+H) + ; Rt = 1.71 min.

Pyridine-2-carboxylic acid (6-methoxy-pyridin-3-yl)-amide dihydrochloride 5-Amino-2-methoxypyridine (4.40 g, 35.4 mmol), dissolved in a small amount of tetrahydrofu- ran, was added slowly to a stirred solution of pyridine-2-carbonyl chloride hydrochloride (7.12 g, 40.0 mmol) in tetrahydrofuran (75 mL). After stirring overnight at room temperature diethyl ether was added. The solids were isolated by suction, washed with diethyl ether and dried in a vacuum oven at 45 °C, yielding the title compound (7.89 g, 75%).

'H NMR (300MHz, CDCI3) : = 3.87 (s, 3H), 6.90 (d, 1 H), 7.03 (br. s, 2 HCI + H20), 7.70 (m, 1H), 8.09 (dt, 1H), 8.17 (d, 1H), 8.22 (dd, 1H), 8. 68 (d, 1H), 8.73 (m, 1H), 10.82 (s, 1H) ; HPLC-MS (Method A): m/z = 230 (M+H) + ; Rt = 2.45 min and 264 + 266; Rt = 3.15 min.

Pyridine-2-carboxylic acid (6-hydroxy-pyridin-3-yl)-amide hydrochloride Pyridine-2-carboxylic acid (6-methoxy-pyridin-3-yl)-amide dihydrochloride (0.66 g, 1.99 mmol) was heated at 180 °C for 10 minutes. After cooling to room temperature, the title com- pound was obtained and used without further purification.

HPLC-MS (Method A): m/z = 216 (M+H) + ; Rt = 2.14 min.

5-Methoxy-pyrimidin-2-ylamine Under a nitrogen atmosphere phosphorus pentachloride (21 g, 0.10 mol) was added por- tionwise to 1,1, 3-trimethoxyethane (12.0 g, 0.10 mol) with stirring and external cooling (ice- bath). After addition was completed, stirring was continued for an additional 30 minutes at room temperature. Dimethylformamide (22.5 mL) was added by means of a dropping funnel, while the reaction mixture was cooled externally with an ice-bath. After completion of the ad- dition, the reaction mixture was heated at 60 °C for 70 minutes. The reaction mixture was then cooled in an ice-bath and methanol (50 mL) was added dropwise. The resulting solution was added dropwise to a stirred solution of sodium hydroxide (24 g) in methanol (80 mL) while cooling in an ice-bath. Guanidine nitrate (20.0 g, 0.16 mol) and sodium hydroxide (7.0 g, 0.175 mol) were added and the solution was stirred for 18 hours at room temperature. Wa- ter (150 mL) was added and the solution was extracted three times with dichloromethane.

The combined organic layers were evaporated in vacuo leaving a brown oil. According to'H NMR analysis a mixture of the desired product and the intermediate ß-dimethylamine-a- methoxyacroleine was obtained. The mixture was dissolved in methanol (100 mL). Guanidine

nitrate (15.0 g, 0.12 mol) and sodium hydroxide (5.25 g, 0.13 mol) were added and the reac- tion mixture was heated at 60 °C for 3 hours, followed by stirring at room temperature for 3 days. Water was added and the solution was extracted three times with dichloromethane.

The combined organic layers were dried over sodium sulphate, filtered and evaporated in vacuo yielding the title compound (5.43 g, 43% yield) as a yellow solid.

'H NMR (300MHz, CDCI3) : 5= 3.80 (s, 3H), 5.08 (br. s, 2H), 8.04 (s, 2H); HPLC-MS (Method A): m/z = 126 (M+H) + ; Rt = 0.39 min.

1- (5-Methoxy-pyrimidin-2-yl)-4, 4-dimethyl-piperidine-2, 6-dione A mixture of 5-methoxy-pyrimidin-2-ylamine (1.00 g, 7.99 mmol) and 3, 3-dimethylglutaric an- hydride (1.14 g, 7.99 mmol) was heated at 180 °C for 9 hours. After cooling to room tempera- ture the reaction mixture was dissolved in a small amount of dichloromethane and purified by flash column chromatography (SiO2, ethyl acetate: heptane 70: 30), yielding the title com- pound (0.79 g, 40% yield) as a white solid.

H NMR (300MHz, CDCI3) : zu 1.23 (s, 6H), 2.67 (s, 4H), 3.97 (s, 3H), 8. 48 (s, 2H); HPLC- MS (Method A): m/z = 250 (M+H) + ; Rt = 1.86 min.

1- (5-Hydroxy-pyrimidin-2-yl)-4, 4-dimethyl-piperidine-2, 6-dione A mixture of 1- (5-methoxy-pyrimidin-2-yl)-4, 4-dimethyl-piperidine-2, 6-dione (0.99 g, 3.97 mmol) and pyridine hydrochloride (1.50 g, 7.99 mmol) was heated at 190 °C for 2.5 hours.

After cooling to room temperature the reaction mixture was dissolved in a small amount of dichloromethane and filtered over a short pad of silicagel and washed with ethyl acetate.

Evaporation of the solvent in vacuo yielded the title compound (0.60 g, 64 % yield) as a white solid.

1H NMR (300MHz, CDCI3) : (5 = 1.23 (s, 6H), 2.65 (s, 4H), 8.42 (s, 2H), 9.94 (br. s, 1H) ; HPLC- MS (Method A): m/z = 236 (M+H) + ; Rt = 1.53 min.

6-Chloro-N-(6-hydroxy-pyridin-3-yl)-nicotinamide A solution of 6-chloro-nicotinoyl chloride (0.40 g, 2.27 mmol) and 5-amino-2-hydroxypyridine hydrochloride (0.33 g, 2.25 mmol) in dry tetrahydrofuran (15mL) was stirred at room tempera-

ture for 1 hour. Saturated sodium bicarbonate (aq) was added and the solution was extracted three times with dichloromethane. The combined organic layers were dried over sodium sul- phate, filtered and evaporated in vacuo. The residue was dissolved in a mixture of methanol (10 mL) and aqueous sodium hydroxide (1 N, 2 mL). After stirring for 2 hours at room tem- perature water was added and the solution was extracted with dichloromethane. The organic layer was dried over sodium sulphate, filtered and evaporated in vacuo, yielding the title compound which was used without further purification.

HPLC-MS (Method A): m/z = 250 (M+H) + ; Rt = 1.52 min.

N- (2, 2-Dimethyl-propyl)-6-hydroxy-nicotinamide A solution of 6-hydroxynicotinic acid (1.39 g, 10.0 mmol), 1-hydroxy-7-azabenztriazole (1.50 g, 11.0 mmol), and 1- (3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (2.11 g, 11.0 mmol) in dimethylformamide (25 mL) was stirred at room temperature for 20 minutes. A solution of 2, 2-dimethylpropylamine (0.96 g, 11.0 mmol) and NN-diisopropylethylamine (1. 42 g, 11.0 mmol) in a small amount of dimethylformamide was added. Stirring was continued for 0.5 hour at room temperature. Ethyl acetate was added and the reaction mixture was ex- tracted twice with water. The solvent was evaporated in vacuo yielding the title compound, which was used without further purification.

HPLC-MS (Method A): m/z = 209 (M+H) + ; Rt = 1.86 min.

3-Chloro-6- (3, 4-dichloro-phenoxy)-pyridazine A solution of 3, 6-dichloropyridazine (4.47 g, 30.0 mmol), 3, 4-dichlorophenol (4.89 g, 30.0 mmol) and potassium hydroxide (1.68 g, 30.0 mmol) in dimethyl sulfoxide (20 mL) was hea- ted at 60 °C overnight. The solvent was removed by evaporation in vacuo. The residue was purified by flash column chromatography (SiO2, ethyl acetate: heptane 50: 50). Small amounts of starting material were removed by kugelrohr distillation. Crystallisation from ethyl aceta- te: heptane yielded the title compound (1.74 g, 21 % yield) as a white solid.

'H NMR (300MHz, CDCI3) : d= 7.10 (dd, 1H), 7.20 (d, 1H), 7.37 (d, 1H), 7.49 (d, 1H), 7.54 (d, 1 H) ; HPLC-MS (Method A): m/z = 275 and 277 (M+H) + ; Rt = 4.00 min.

6- (3, 4-dichloro-phenoxy)-pyridazin-3-ol A solution of 3-chloro-6- (3, 4-dichloro-phenoxy)-pyridazine (1.74 g, 6.32 mmol) in formic acid (25 mL) was heated at 100 °C for 3 hours. The solvent was removed by evaporation in vacuo yielding the title compound, which was used without further purification.

HPLC-MS (Method A): mlz = 257 (M+H) + ; Rt = 3.13 min.

(4-Hydroxy-piperidin-1-yl)-imidazol-1-yl-methanone A solution of 4-hydroxypiperidine (20.0 g, 198 mmol) and N,N'-carbonyldiimidazole (32.06 g, 198 mmol) in tetrahydrofuran (250 mL) was heated overnight at reflux, followed by stirring at room temperature for two days. The solvent was evaporated yielding the title compound, which was used without further purification.

HPLC-MS (Method A): mlz = 196 (M+H) + ; Rt = 0.39 min.

[4- (tert-Butyl-dimethyl-silanyloxy)-piperidin-1-yl]-imidazol-1- yl-methanone tert-Butyldimethylsilyl chloride (30.14 g, 0.20 mol) was added to a stirred solution of (4- hydroxy-piperidin-1-yl)-imidazol-1-yl-methanone (39. 05 g, 0.20 mol) in dimethylformamide (200 mL). After stirring for 3 days at room temperature, the solvent was removed by evapora- tion in vacuo. The residue was redissolved in dichloromethane, extracted twice with water, dried over sodium sulphate, filtered and evaporated in vacuo, yielding the title compound, which was used without further purification.

1H NMR (300MHz, CDCI3) : 8 = 0.07 (s, 6H), 0.90 (s, 9H), 1.64 (m, 2H), 1.81 (m, 2H), 3.53- 3.74 (m, 4H), 4.06 (m, 1H), 7.07 (m, 1H), 7.18 (m, 1H), 7.86 (m, 1H) ; HPLC-MS (Method A): m/z = 310 (M+H) +; Rt = 3.40 min. <BR> <BR> <BR> <BR> <BR> <P>3- [4- (tert-Butyl-dimethyl-silanyloxy)-piperidine-1-carbonyl]-1-me thyl-3H-imidazol-1-ium iodide Methyl iodide (113.5 g, 0.80 mol) was added to a stirred solution of [4-(teff-butyl-dimethyl- silanyloxy)-piperidin-1-yl]-imidazol-1-yl-methanone (61.9 g, 0.20 mol) in acetonitrile (400 mL).

After stirring overnight at room temperature the solvent was evaporated in vacuo. The resi-

due was washed with ethyl acetate: heptane and dried in a vacuum oven at 45 °C, yielding the title compound (60.92 g, 68% yield over three steps) as a white solid 1 H NMR (300MHz, CDC13) : 6 = 0.08 (s, 6H), 0.88 (s, 9H), 1.57 (m, 2H), 1.83 (m, 2H), 3.45 (m, 2H), 3.65 (m, 2H), 3.93 (s, 3H), 4.06 (m, 1H), 7.87 (m, 1H), 8.03 (m, 1H), 9.56 (s, 1H) ; HPLC-MS (Method A): m/z = 324 (M-l-) +; Rt = 2.95 min.

4-Chloro-N-(6-hydroxy-pyridin-3-yl)-benzamide 4-Chlorobenzoyl chloride (1.75 g, 10.0 mmol) was added carefully to a stirred solution of 5- amino-2-methoxypyridine (1.24 g, 10.0 mmol) in dichloromethane (10 mL). After stirring overnight at room temperature, the solvent is evaporated in vacuo and the residue is heated in a pre-heated kugelrohr oven at 200 °C for 5-10 minutes under house-vacuum (around 20 mbar) yielding the title compound, which was used without further purification.

HPLC-MS (Method A): m/z = 249 (M+H) + ; Rt = 2.18 min.

4-Fluoro-N- (6-hydroxy-pyridin-3-yl)-benzamide Starting from 4-fluorobenzoyl chloride (1.59 g, 10.0 mmol) and using the procedure as de- scribed for the preparation of 4-Chloro-N-(6-hydroxy-pyridin-3-yl)-benzamide yielded the title compound, which was used without further purification.

HPLC-MS (Method A): m/z = 233 (M+H) + ; Rt = 1.76 min.

N-(6-Hydroxy-pyridin-3-yl)-3-methoxy-benzamide Starting from 3-methoxybenzoyl chloride (1.71 g, 10.0 mmol) and using the procedure as de- scribed for the preparation of 4-Chloro-N-(6-hydroxy-pyridin-3-yl)-benzamide yielded the title compound, which was used without further purification.

HPLC-MS (Method A) : m/z = 245 (M+H) + ; Rt = 1. 81 min.

N- (6-Hydroxy-pyridin-3-yl)-4-methoxy-benzamide Starting from 4-methoxybenzoyl chloride (1.71 g, 10.0 mmol) and using the procedure as de- scribed for the preparation of 4-Chloro-N-(6-hydroxy-pyridin-3-yl)-benzamide yielded the title compound, which was used without further purification.

HPLC-MS (Method A): m/z = 245 (M+H) + ; Rt = 1.72 min.

N- (6-Hydroxy-pyridin-3-yl)-4-methoxy-benzamide Starting from 2, 4-dichlorobenzoyl chloride (2.10 g, 10.0 mmol) and using the procedure as described for the preparation of 4-Chloro-N- (6-hydroxy-pyridin-3-yl)-benzamide yielded the title compound, which was used without further purification.

HPLC-MS (Method A): m/z = 283 (M+H) + ; Rt = 2.28 min.

N-(6-Hydroxy-pyridin-3-yl)-4-trifluoromethyl-benzamide Starting from4-trifluoromethylbenzoyl chloride (2.09 g, 10.0 mmol) and using the procedure as described for the preparation of 4-Chloro-N-(6-hydroxy-pyridin-3-yl)-benzamide yielded the title compound, which was used without further purification.

HPLC-MS (Method A): mlz = 283 (M+H)+ ; Rt = 2.28 min.

6'-Hydroxy-4, 5-dihydro-3H- [1, 3'] bipyridinyl-2, 6-dione Glutaric anhydride (1.14 g, 10.0 mmol) was added to a solution of 5-amino-2- methoxypyridine (1.24 g, 10.0 mmol) in dichloromethane (25 mL). After standing for 1 hour at room temperature, thionyl chloride (5.95 g, 50.0 mmol) was added, followed by heating to reflux for 0.5 hour. The solvent and excess thionyl chloride were evaporated in vacuo, yield- ing 4- (6-methoxy-pyridin-3-ylcarbamoyl)-butyryl chloride, which was used without further puri- fication.

'H NMR (300MHz, Ceci3) : 8 = 1.81 (quintet, 2H), 2.28 (t, 2H), 2.38 (t, 2H), 3.87 (s, 3H), 6.91 (d, 1H), 8.00 (dd, 1H), 8.43 (d, 1H), 10.24 (s, 1H, NH).; HPLC-MS (Method A): m/z = 253 (M+H) + ; Rt = 1.94 min. (analysed as methyl ester).

The crude 4- (6-methoxy-pyridin-3-ylcarbamoyl)-butyryl chloride was redissolved in dichloro- methane (25 mL). Thionyl chloride (5.95 g, 50 mmol) was added and the solution was heated to reflux overnight. The solvent and excess thionyl chloride were evaporated in vacuo, yield- ing 6'-methoxy-4, 5-dihydro-3H [1, 3'] bipyridinyl-2, 6-dione hydrochloride, which was used without further purification.

H NMR (300MHz, CDCI3) : 8 = 2.00 (quintet, 2H), 2.72 (t, 4H), 3.88 (s, 3H), 6.90 (d, 1 H), 7.51 (dd, 1 H), 6.92 (d, 1 H), 9.71 (br. s, HCI + H2O) ; HPLC-MS (Method A): m/z = 221 (M+H) + ; Rt = 1. 38 min.

The crude 6'-methoxy-4, 5-dihydro-3H- [1, 3'] bipyridinyl-2, 6-dione hydrochloride (2.57 g, 10.0 mmol) was heated in a pre-heated kugerohr oven at 180 °C for 5 minutes. After cooling to room temperature the product was purified by flash column chromatography (Si02, ethyl ace- tate: acetone 25: 75), yielding the title compound (0. 48 g, 23% yield) as a white solid.

'H NMR (300MHz, CDCI3) : 6= 2.10 (quintet, 2H), 2.81 (t, 4H), 3.53 (br. s, 3H), 7.12 (br. s, 1 H), 7.27 (m, 1 H), 7.38 (m, 4H), 7.50 (d, 1 H), 8.09 (s, 1 H) ; HPLC-MS (Method A) : m/z = 340 (M+H) + ; Rt = 2.89 min.

1-(6-Methoxy-pyridin-3-yl)-pyrrolidine-2, 5-dione A mixture of 5-amino-2-methoxypyridine (1.24 g, 10.0 mmol) and succinic anhydride (1.00 g, 10.0 mmol) was heated with a heat gun for 10 minutes. After cooling to room temperature the product was purified by flash column chromatography (SiO2, ethyl acetate: acetone 25: 75).

Evaporation of the solvent yielded the title compound as a white solid.

'H NMR (300MHz, CDCI3) : 6= 2.92 (s, 4H), 3.96 (s, 3H), 6.82 (d, 1H), 7.50 (dd, 1H), 8.11 (d, 1 H) ; HPLC-MS (Method A): m/z = 207 (M+H) + ; Rt = 1. 26 min.

1-(6-Hydroxy-pyridin-3-yl)-pyrrolidine-2, 5-dione 1- (6-Methoxy-pyridin-3-yl)-pyrrolidine-2, 5-dione was dissolved in tetrahydrofuran and HCI- gas was bubbled into the solution for 5 minutes. The solvent was evaporated in vacuo and the residue was heated for 10 minutes at 180 °C in a pre-heated kugelrohr oven. After cool- ing to room temperature the residue was purified by flash column chromatography (SiO2), yielding the title compound (285 mg, 15% yield over two steps).

'H NMR (400MHz, DMSO-d6) : 3= 2.72 (s, 4H), 6.40 (d, 1H), 7.31 (dd, 1H), 7.39 (d, 1H), 11. 76 (br. s, 1 H, OH); HPLC-MS (Method A): m/z = 193 (M+H)+ ; Rt = 0.37 min.

2-Methoxy-5- (5-trifluoromethyl-pyridin-2-yloxy)-pyridine A solution of 5-hydroxy-2-methoxypyridine (1.25 g, 10.0 mmol), 2-chloro-5-trifluoro- methylpyridine (1.82 g, 10.0 mmol) and potassium hydroxide (85% pure, 1.08 g, 10.0 mmol) in dimethyl sulfoxide (25 mL) was heated at 90 °C for 2.5 hours. The solution was cooled to room temperature and poured slowly into water (200 mL). After cooling with an external ice- bath, the precipitate was collected by suction, washed thoroughly with water and dried in a vacuum oven at 45 °C, yielding the title compound (2.56 g, 95% yield). oh NMR (300MHz, Cd13) : 3 = 3.95 (s, 3H), 6.80 (d, 1H), 7.04 (d, 1H), 7.41 (dd, 1H), 7.91 (dd, 1 H), 8. 03 (d, 1 H), 8.40 (d, 1 H) ; HPLC-MS (Method A): mlz = 271 (M+H) + ; Rt = 3.88 min.

5- (5-Trifluoromethyl-pyridin-2-yloxy)-pyridin-2-ol A mixture of 2-methoxy-5- (5-trifluoromethyl-pyridin-2-yloxy)-pyridine (0.28 g, 1.04 mmol) and pyridine hydrochloride (1.00 g, 8. 65 mmol) was heated in a kugelrohr oven at 200 °C for 10 minutes. After cooling to room temperature, the reaction mixture is dissolved in dichloro- methane and extracted with water, dried over sodium sulphate, filtered and evaporated in vacuo, yielding the title compound (180 mg, 68% yield) as a white solid.

'H NMR (300MHz, CDC13) : 6= 6.63 (m, 1H), 7.06 (d, 1H), 7.42 (m, 2H), 7.92 (dd, 1H), 8.42 (d, 1 H) ; HPLC-MS (Method A): m/z = 257 (M+H) + ; Rt = 2.32 min.

5- (3, 5-Dichloro-pyridin-2-yloxy)-2-methoxy-pyridine A solution of 5-hydroxy-2-methoxypyridine (1.25 g, 10.0 mmol), 2,3, 5-trichloropyridine (1.82 g, 10.0 mmol) and potassium hydroxide (85% pure, 1.08 g, 10.0 mmol) in dimethyl sulfoxide (25 mL) was heated at 90 °C for 1.5 hours. The solution was poured slowly into water (200 mL). The precipitate was collected by suction, washed thoroughly with water and dried in a vacuum oven at 45 °C, yielding the title compound (2.39 g, 88% yield). oh NMR (300MHz, CDC13) : dz 3.95 (s, 3H), 6.80 (d, 1H), 7.41 (dd, 1H), 7.77 (d, 1H), 7.93 (d, 1 H), 8.03 (d, 1 H) ; HPLC-MS (Method A): m/z = 271 (M+H) + ; Rt = 4.18 min.

5- (3, 5-Dichloro-pyridin-2-yloxy)-pyridin-2-ol A mixture of 5- (3, 5-dichloro-pyridin-2-yloxy)-2-methoxy-pyridine (2.39 g, 8.82 mmol) and py- ridine hydrochloride (7.00 g, 60.6 mmol) was heated in a kugelrohr apparatus at 200 °C for 25 minutes. After cooling to room temperature dichloromethane and water were added. The solid material, which was insoluble in dichloromethane and water, was isolated by suction and dried in a vacuum oven at 45 °C, yielding the title compound, which was used without further purification.

HPLC-MS (Method A): m/z = 257 (M+H) + ; Rt = 2.53 min.

4, 4-Dimethyl-3, 4,5, 6-tetrahydro-2H- [1, 3'] bipyridinyl-6'-ol Under a nitrogen atmosphere lithium aluminium hydride (1.90 g, 50.0 mmol) was added por- tionwise to a stirred suspension of 6'-methoxy-4, 4-dimethyl-4, 5-dihydro-3H- [1, 3'] bipyridinyl- 2,6-dione (2.85 g, 10.0 mmol) in dry diethyl ether (100 mL). After stirring for 3 hours at room temperature, water (1.90 mL), 15% aqueous sodium hydroxide (1.90 mL) and water (5.70 mL) were added respectively. After stirring for 1 hour at room temperature the salts were re- moved by filtration and washed three times with diethyl ether. The solvent was evaporated in vacuo and the residue was purified by flash column chromatography (SiO2, dichloromethane followed by ethyl acetate/heptane 25/75) yielding the title compound (1.28 g, 58% yield) as a yellow oil.

'H NMR (300MHz, CDCI3) : d= 0.98 (s, 6H), 1.53 (m, 4H), 3.03 (m, 4H), 3. 89 (s, 3H), 6.67 (d, 1H), 7.30 (dd, 1H), 7. 80 (d, 1H) ; HPLC-MS (Method A): m/z = 221 (M+H) +; Rt = 2.14 min.

4, 4'Dimethyl-3, 4,5, 6-tetrahydro-2H- [1, 3'] bipyridinyl-6'-ol A mixture of 6'-methoxy-4, 4-dimethyl-3, 4,5, 6-tetrahydro-2H- [1, 3'] bipyridinyl (1.28 g, 5.81 mmol) and pyridine hydrochloride (5.00 g, 43.3 mmol) was heated in a kugelrohr oven at 200 °C for 15 minutes. After cooling to room temperature water was added and the solution was made slightly basic with aqueous 1 N sodium hydroxide. The solution was extracted three times with dichloromethane and the combined organic layers were dried over sodium sul- phate, filtered and evaporated in vacuo, yielding the title compound (0.86 g, 72% yield).

HPLC-MS (Method A): m/z = 207 (M+H) + ; Rt = 1.31 min.

Methyl-phenyl-carbamic acid 4-amino-phenyl ester To a solution of N-Boc protected 4-aminophenol (10 mmol) in CH2CI2 (50 mL) was added N- methyl-N-phenylcarbamoyl chloride (15 mmol) and DABCO (15 mmol) at room temperature.

The reaction mixture was stirred for 16 hours at rt, added CH2CI2 (20 mL) and washed with aqueous citric acid (5%) and brine. The organic phase was separated, dried (MgS04) and evaporated to give the crude product which was purified by FC (Quad flash 40 MeOH-CH2CI2 5: 95). The purified intermediate was dissolved in CH2C12 (90 mL). Addition of TFA (6 mL) and stirring for 4 h. The reaction mixture was evaporated to dryness and dried in vacuo at 50 °C overnight producing the title compound in 72% yield as colorless crystals.

HPLC-MS: m/z = 243.1 (M+1); Rt = 2.02 min.

Example 1 (General procedure 9) 4- [ (1, 3-Benzodioxol-5-yl) methyl]-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2- yloxy)-phenyl ester The hydrochloride of the title compound was prepared from 4- (5-trifluoromethyl-pyridin-2- yloxy)-phenyl chloroformate and 1-piperonylpiperazine, yield 67 %. Recrystallisation from 96 % ethanol gave white crystals, m. p. 239-240 °C ; HPLC-MS m/z = 502 (M+H), 524 (M+Na), Rt= 3.3 min.;. ;'H NMR (DMSO-d6) : 611. 64 (br, 1H, NH), 8.62-8. 52 (br, 1H, py-H6), 8.31- 8.19 (m, 1H, py-H4), 7.40-7. 15 (m, 6H, py-H3 + C6H4+ 1 arom.), 7.15-6. 93 (m, 2H, arom), 4.53-3. 96 (br, 4H, CH2 at 4.26 + 2 CH), 3.80-2. 89 (br, 6H, water at 3.38 + 4C-H) ; IR (KBr) : v 1724 (C=O).

Example 2 (General procedure 1) Methyl-phenyl-carbamic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester The title compound was prepared from 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenol and N- methyl-N-phenylcarbamoyl chloride. The crude product was purified by preparative HPLC (36%, white crystals). HPLC-MS m/z = 389.1 (M+1), Rt: 5.13 min.

$ (300MHz ; CDCI3) : 3.43 (s, 3H), 6.98 (d, 1 H, J 8.7), 7.09-7. 22 (m, 4H), 7.30-7. 34 (m, 1 H), 7.35 (d, 2H, J 7. 1), 7.40 (t, 2H, J 6. 8), 7. 88 (dd, 1 H, J 8. 7 and 2. 3), 8.42 (s, 1H).

Example 3 (General procedure 1) Methyl-phenyl-carbamic acid 3- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester

The title compound was prepared from 3- (5-trifluoromethyl-pyridin-2-yloxy)-phenol and N- methyl-N-phenylcarbamoyl chloride. The crude product was subjected to flash chromatogra- phy (Quad flash 25, dichlormethane) (89%, oil). HPLC-MS m/z = 389.1 (M+1), Rt: 5.08 min.

#H (300MHz ; DMSO-d6) : 3.34 (s, 3H), 7.00-7. 15 (m, 3H), 7.27 (t, 2H), 7.35-7. 55 (m, 5H), 8.24 (dd, 1 H), 8. 58 (s, 1 H).

Example 4 (General procedure 1) Methyl-phenyl-carbamic acid 4- (3, 5-dichloro-pyridin-2-yloxy)-phenyl ester The title compound was prepared from 4- (3, 5-dichloro-pyridin-2-yloxy)-phenol and N-methyl- N-phenylcarbamoyl chloride. The crude product was purified by preparative HPLC (53%, crystals). HPLC-MS m/z = 389.1 (M+1), Rt: 5.1 min.

4 (300MHz ; CDCI3) : 3.43 (s, 3H), 7.07-7. 20 (m, 4H), 7.27-7. 48 (m, 5H), 7.75 (d, 1 H, J 2.2), 7.93 (d, 1 H, J 2.2).

Example 5 (General procedure 1) Methyl-phenyl-carbamic acid 4- (5-trifluoromethyl-pyridin-2-ylamino)-phenyl ester The title compound was prepared from 4- (5-trifluoromethyl-pyridin-2-ylamino)-phenol and N- methyl-N-phenylcarbamoyl chloride. The crude product was purified by preparative HPLC to give the title product (32%, white crystals). HPLC-MS m/z = 388.2 (M+1), Rt: 4.72 min. i (300MHz ; CDCI3) : 3. 44 (s, 3H), 6.76 (d, 1H), 6.81 (bs, 1H), 7.12 (d, 2H), 7. 27-7. 45 (m, 6H), 7.63 (dd, 1 H), 8.42 (bs, 1 H).

Example 6 (General procedure 1) Methyl-phenyl-carbamic acid 4- (3, 5-dichloro-pyridin-4-yloxy)-phenyl ester The title compound was prepared from 4- (3, 5-dichloro-pyridine-4-yloxy)-phenol and N- methyl-N-phenylcarbamoyl chloride. The crude product was purified by preparative HPLC (41%, white crystals). HPLC-MS m/z = 389.1 (M+1), Rt: 4.97 min. i (300MHz ; CDC13) : 3.42 (s, 3H), 6.81 (d, 2H, J 9.0), 7.07 (d, 2H, J 7.9), 7.25-7. 43 (M, 5H), 8.55 (s, 2H).

Example 7 (General procedure 1)

Methyl-phenyl-carbamic acid 4- (4-trifluoromethyl-phenoxy)-phenyl ester The title compound was prepared from 4- (4-trifluoromethyl-phenoxy)-phenol and N-methyl-N- phenylcarbamoyl chloride. The crude product was purified by preparative HPLC (78%, white crystals). HPLC-MS m/z = 388.0 (M+1), Rt: 5.59 min.

$§ (300MHz ; CDCI3) : 3.43 (s, 3H), 7.02 (d, 4H, J 8.7), 7.14 (d, 2H, J 8.7), 7.31 (1H, d, J 6.8), 7.35 (d, 2H, J 7.2), 7.41 (t, 2H, J 7.1), 7.55 (d, 2H, J 8.6).

Example 8 (General procedure 1) Methyl-phenyl-carbamic acid 4- (3-trifluoromethyl-phenoxy)-phenyl ester The title compound was prepared from 4- (3-trifluoromethyl-phenoxy)-phenol and N-methyl-N- phenylcarbamoyl chloride. The crude product was purified by preparative HPLC (73%, white crystals). HPLC-MS m/z = 388.2 (M+1), Rt: 5.37 min.

Example 9 (General procedure 1) Methyl-phenyl-carbamic acid 4- (2-cyano-5-trifluoromethyl-pyridine-3-yloxy)-phenyl ester The title compound was prepared from 4- (2-cyano-5-trifluoromethyl-pyridin-3-yloxy)-phenol and N-methyl-N-phenylcarbamoyl chloride. The crude product was purified by preparative HPLC (74%, colourless oil). HPLC-MS m/z = 414. 1 (M+1), Rt: 4. 8 min.

4i (300MHz ; CDCI3) : 3. 44 (s, 3H), 7.11 (d, 2H, J 9), 7. 32-7. 1 (m, 3H), 7.32-7. 50 (m, 5H), 8. 63 (s, 1H).

Example 10 (General procedure 1) Methyl-phenyl-carbamic acid 2-benzenesulfonyl-4- (3-chloro-5-trifluoromethyl-pyridine-2- yloxy)-phenyl ester The title compound was prepared from 2-benzenesulfonyl-4- (3-chloro-5-trifluoromethyl- pyridine-2-yloxy)-phenol and N-methyl-N-phenylcarbamoyl chloride. The crude product was purified by preparative HPLC (68%, white crystals). HPLC-MS m/z = 563.1 (M+1), Rt: 5.3 min. i (300MHz ; CDCI3) : 3.44 (s, 3H), 7.20-7. 50 (m, 12H), 7.91 (bs, 1H), 8.00 (d, 1H, J 2.3), 8.23 (s, 1H).

Example 11 (General procedure 1) Methyl-phenyl-carbamic acid 4-tert-butoxy-phenyl ester The title compound was prepared from 4-tert-butoxy-phenol and N-methyl-N- phenylcarbamoyl chloride. The crude product was subjected to flash chromatography (Quad12/25, flash 12, dichloromethane) followed by a recrystallization from ethanol (41%, crystals). HPLC-MS m/z = 300.3 (M+1), Rt: 4.7 min. i (300MHz ; CDCI3) : 1.31 (s, 9H), 3.41 (s, 3H), 6.90-7. 07 (m, 4H), 7.20-7. 28 (m, 1 H), 7.32- 7.43 (m, 4H).

Example 12 (General procedure 1) Methyl-phenyl-carbamic acid 3- (4-fluorobenzyl)-4-methyl-2-oxo-2H-chromen-7-yi ester The title compound was prepared from 3- (4-fluorobenzyl)-7-hydroxy-4-methyl-2H-chromen-2- one and N-methyl-N-phenylcarbamoyl chloride.

The crude product was of high purity and tested without purification (&num 100%, crystals); mp: 185-186°C. HPLC-MS m/z = 418.2 (M+1), Rt: 5.2 min.

(300MHz ; CDCI3) : 2.43 (s, 3H), 3.43 (s, 3H), 6.95 (dt, 2H, J 8.7 and 2.3), 7.10 (m, 2H), 7.21 (dt, 2H, J 7.2 and 2.3), 7.27-7. 45 (m, 5H), 7.58 (d, 1 H, J 8.3).

Example 13 (General procedure 1) Methyl-phenyl-carbamic acid 4-phenoxy-phenyl ester The title compound was prepared from 4-phenoxy-phenol and N-methyl-N-phenylcarbamoyl chloride. The crude product was recrystallized (ethanol/water) (86%, white crystals). HPLC- MS m/z = 320.1 (M+1), Rt: 5.13 min.

& (300MHz ; CDCI3) : 3.43 (s, 3H), 6.94-7. 02 (m, 4H), 7.08 (t, 2H, J 6.8), 7.04-7. 12 (m, 1H), 7.32 (t, 2H, J 7.5), 7.28-7. 35 (m, 1 H), 7.35-7. 45 (m, 4H).

Example 14 (General procedure 1) Methyl-phenyl-carbamic acid 4- (4-chlorobenzoyl)-phenyl ester The title compound was prepared from 4- (4-chlorobenzoyl)-phenol and N-methyl-N- phenylcarbamoyl chloride. The crude product was recrystallized (ethanol/water) (90%, white crystals). HPLC-MS m/z = 366.1 (M+1), Rt: 5.19 min.

i (300MHz ; CDCI3) : 3.45 (s, 3H), 7.19-7. 37 (m, 4H), 7.40 (t, 2H, J 7.2), 7.37-7. 40 (m, 1H), 7.46 (dt, 2H, J 8.7 and 2,3), 7.73 (dt, 2H, J 8.7 and 2.2), 7.79 (d, 2H, J 8.7).

Example 15 (General procedure 1) Methyl-phenyl-carbamic acid 4- (3-chloro-5-trifluoromethyl)-pyridine-2-yloxy)-phenyl ester The title compound was prepared from 4- (3-chloro-5-trifluoromethyl)-pyridine-2-yloxy)-phenol and N-methyl-N-phenylcarbamoyl chloride. Prepared as described in general procedure 1.

The crude product was recrystallized (ethanol/water (78%, white crystals). HPLC-MS m/z = 423.1 (M+1), Rt: 5.31 min.

SH (300MHz ; CDCI3) : 3.43 (s, 3H), 7.10-7. 23 (m, 4H), 7.27 (t, 1H, J 6.8), 7.35 (d, 2H, J 7.5), 7.41 (t, 2H, J 7.4), 7.96 (d, 1H, J 1.9), 8.23 (bs, 1H).

Example 16 (General procedure 1) Methyl-phenyl-carbamic acid 4- [4- (4-chloro-phenyl)-thiazol-2-yl]-phenyl ester The title compound was prepared from 4- [4- (4-chloro-phenyl)-thiazol-2-yl]-phenol and N- methyl-N-phenylcarbamoyl chloride. The crude product was recrystallized (ethanol/water) (59%, white crystals). HPLC-MS m/z = 421.1 (M+1), Rt: 5.85 min 4i (300MHz ; CDCI3) : 3.45 (s, 3H), 7.18-7. 25 (m, 2H), 7.27-7. 33 (m, 1H), 7.34-7. 41 (m, 4H), 7.43 (d, 2H, J 6. 8), 7.41-7. 46 (m, 1H), 7.92 (dt, 2H, J 8. 6 and 2. 2), 8.00 (d, 2H, J 8. 7).

Example 17 (General procedure 1) Methyl-phenyl-carbamic acid 4-pyrrol-1-yl-phenyl ester The title compound was prepared from 4-pyrrol-1-yl-phenol and N-methyl-N- phenylcarbamoyl chloride. The crude product was recrystallized (ethanol/water) (27%, off- white crystals). HPLC-MS m/z = 293.2 (M+1), Rt: 4.51 min. i (300MHz ; CDC13) : 3.44 (s, 3H), 6.33 (t, 2H, J 2.2), 7.03 (t, 2H, J 2.2), 7.17 (bd, 2H, J 8.3), 7.29 (d, 1 H, J 6.8), 7.31-7. 38 (m, 4H), 7.41 (t, 2H, J 6.8).

Example 17a (General procedure 1) Methyl-phenyl-carbamic acid 4-imidazol-1-yl-phenyl ester The title compound was prepared from 4-imidazol-1-yl-phenol and N-methyl-N-

phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC (4%, clear oil). HPLC-MS m/z = 294.1 (M+1), Rt: 2.25 min.

SH (300MHz ; CDCI3) : 3.44 (s, 3H), 7.27-7. 39 (m, 4H), 7.39-7. 50 (m, 5H), 7.53 (bs, 1 H), 8.83 (bs, 1H).

Example 18 (General procedure 1) Methyl-phenyl-carbamic acid 4- (3-chloro-5-trifluoromethyl)-pyridine-2-ylmethyl)-phenyl ester The title compound was prepared from 4- (3-chloro-5-trifluoromethyl)-pyridine-2-ylmethyl)- phenol and N-methyl-N-phenylcarbamoyl chloride.

The crude product was recrystallized (ethanol/water) (74%, white crystals). HPLC-MS m/z = 421.1 (M+1), Rt: 5.23 min. n (300MHz ; CDC13) : 3.40 (s, 3H), 4.33 (s, 2H), 7.03 (d, 2H, J 8. 3), 7. 20-7.30 (m, 3H), 7.3 (d, 2H, J 7.2), 7.38 (t, 2H, J 7.2), 7. 87 (d, 1 H, J 1.5), 8.69 (bs, 1 H,).

Example 19 (General procedure 1) Methyl-phenyl-carbamic acid 4-trifluoromethylsulfanyl-phenyl ester The title compound was prepared from 4-trifluoromethylsulfanyl-phenol and N-methyl-N- phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC (70%, clear oil). HPLC-MS m/z = 328.0 (M+1), Rt: 5.16 min.

8H (300MHz ; CDCI3) : 3.42 (s, 3H), 7.19 (d, 2H, J 6.4), 7.26-7. 7.37 (m, 3H), 7.41 (t, 2H, J 7.9), 7.63 (d, 2H, J 8. 3).

Example 20 (General procedure 1) Methyl-phenyl-carbamic acid 4-pentafluoromethyloxy-phenyl ester The title compound was prepared from 4-pentafluoromethyloxy-phenol and N-methyl-N- phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC (66%, clear oil). HPLC-MS m/z = 362.0 (M+1), Rt: 5.31 min. i (300MHz ; CDCI3) : 3. 42 (s, 3H), 7.10-7. 22 (m, 4H), 7.29 (d, 1H, J 7. 2), 7.34 (d, 2H, J 7.1), 7.41 (t, 2H, J7. 1).

Example 21 (General procedure 1) Methyl-phenyl-carbamic acid 4-benzyloxy-phenyl ester

The title compound was prepared from 4-benzyloxy-phenol and N-methyl-N- phenylcarbamoyl chloride. The crude product was recrystallized (ethanol/water) (83%, white crystals). HPLC-MS m/z = 334.2 (M+1), Rt: 4.88 min. i (300MHz ; CDCI3) : 3.41 (s, 3H), 5.03 (s, 2H), 6.92 (dt, 2H, J 9.0 and 2.2), 7.02 (d, 2H, J 8.7), 7.26-7. 34 (m, 2H), 7.34-7. 38 (m, 4H), 7.38-7. 44, m, 4H).

Example 22 (General procedure 1) Methyl-phenyl-carbamic acid 4-benzyl-phenyl ester The title compound was prepared from 4-benzyl-phenol and N-methyl-N-phenylcarbamoyl chloride. The crude product was recrystallized (ethanol/water) (56%, white crystals). HPLC- MS m/z = 318. 1 (M+1), Rt: 5.05 min. i (300MHz ; CDCI3) : 3.41 (s, 3H), 3.95 (s, 2H), 7.02 (d, 2H), 7.12-7. 19 (m, 5H), 7.20-7. 25 (m, 2H), 7.26-7. 28 (m, 1H), 7.28-7. 34 (m, 1H), 7. 34-7. 42 (m, 3H).

Example 23 (General procedure 1) Methyl-phenyl-carbamic acid 4'-cyano-biphenyl-4-yl-ester The title compound was prepared from 4-hydroxy-4-biphenylcarbonitrile and N-methyl-N- phenylcarbamoyl chloride applying procedure 1. The crude product was recrystallized (etha- nol/water) (87%, white crystals). HPLC-MS m/z = 329.2 (M+1), Rt: 4.63 min. i (300MHz ; CDCI3) : 3.44 (s, 3H), 7.18-7. 26 (m, 2H), 7.26-7. 32 (m, 2H), 7.34-7. 46 (m, 4H), 7.56 (d, 2H), 7.64 (d, 2H), 7.712 (d, 2H).

Example 24 (General procedure 1) Methyl-phenyl-carbamic acid 4'-bromo-biphenyl-4-yl-ester The title compound was prepared from 4-bromo-4'-hydroxybiphenyl and N-methyl-N- phenylcarbamoyl chloride. The crude product was recrystallized (ethanol) (72%, white crys- tals). HPLC-MS m/z = 382.0) (M+1), Rt: 5.41 min. ii (300MHz ; CDCI3) : 3.44 (s, 3H), 7.15-7. 23 (d, 2H), 7.26-7. 31 (m, 1H), 7.34-7. 45 (m, 6H), 7.47. 7.57 (m, 4H).

Example 25 (General procedure 1)

Methyl-phenyl-carbamic acid biphenyl-4-yl-ester The title compound was prepared from 4-hydroxybiphenyl and N-methyl-N-phenylcarbamoyl chloride applying. The crude product was recrystallized (ethanol) (75%, white crystals).

HPLC-MS m/z = 304.2 (M+1), Rt: 4.95 min. i (300MHz ; CDCI3) : 3.45 (s, 3H), 7.19 (d, 2H), 7.26-7. 37 (m, 2H), 7.37-7. 46 (m, 6H), 7.55 (d, 4H).

Example 26 (General procedure 1) Methyl-phenyl-carbamic acid 4- [3- (4-chlorophenyl)-ureido]-phenyl ester The title compound was prepared from 4- [3- (4-chlorophenyl)-ureido]-phenol and N-methyl-N- phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC (33%, off- white crystals). HPLC-MS m/z = 396.1 (M+1), Rt: 4.40 min.

<5n (300MHz ; CDCI3) : 3.52 (s, 3H), 6. 85-7. 03 (m, 7H), 7.09 (d, 2H), 7.30-7. 50 (m, 6H).

Example 27 (General procedure 1) Methyl-phenyl-carbamic acid 4- (4-nitro-phenoxy)-phenyl ester The title compound was prepared from 4- (4-nitro-phenoxy)-phenol and N-methyl-N- phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC (71%, white crystals). HPLC-MS m/z = 365.0 (M+1), Rt: 4.83 min.

#H(300MHz ; CDC13) : 3.44 (s, 3H), 7.00 (d, 2H), 7.06 (d, 2H), 7.26-7. 32 (m, 1 H), 7.33-7. 49 (m, 4H), 8. 20 (dt, 2H).

Example 28 (General procedure 1) Methyl-phenyl-carbamic acid 4-heptylsulfanyl-phenyl ester The title compound was prepared from 4-heptylsulfanyl-phenol and N-methyl-N- phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC (74%, col- ourless oil, HPLC-MS m/z = 358.2 (M+1), Rt: 6.21 min.

& (200MHz ; CDCI3) : 0.87 (t, 3H), 1.15-1. 50 (m, 8H), 1.50-1. 75 (m, 2H), 2. 86 (t, 2H), 3.41 (s, 3H), 7.04 (d, 2H), 7.15-7. 50 (m, 7H).

Example 29 (General procedure 1)

Methyl-phenyl-carbamic acid 4-butoxy-phenyl ester The title compound was prepared from 4-butoxy-phenol and N-methyl-N-phenylcarbamoyl chloride. The crude product was recrystallized from ethanol (22%, white crystals). HPLC-MS m/z = 300.1 (M+1), Rt: 5.20. i (300MHz ; CDCI3) : 0.96 (t, 3H), 1.45 (qi, 2H), 1.74 (qi, 2H), 3.41 (s, 3H), 3.92 (t, 2H), 6.84 (d, 2H), 6.99 (d, 2H), 7.25-7. 27 (m, 1 H), 7.30-7. 45 (m, 4H).

Example 30 (General procedure 1) Methyl-phenyl-carbamic acid 4- (4-chloro-benzenesulfonyl)-phenyl ester The title compound was prepared from 4- (4-chloro-benzenesulfonyl)-phenol and N-methyl-N- phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC (46%, col- ourless oil). HPLC-MS m/z = 402.1 (M+1), Rt: 4.65 min. i (200MHz ; CDCI3) : 3.41 (s, 3H), 7.21-7. 35 (m, 5H), 7.39 (d, 2H), 7.46 (dt, 2H, 7. 84 (dt, 2H) 7,90 (d, 2H).

Example 31 (General procedure 1) Methyl-phenyl-carbamic acid 4- (4-chloromethyl-thiazol-2-yl)-phenyl ester The title compound was prepared from 4- (4-chloromethyl-thiazol-2-yl)-phenol and N-methyl- N-phenylcarbamoyl chloride. The aqueous phase was adjusted to PH 7.0 (phosphate buffer) before extraction with ethyl acetate. The crude product was subjected to preparative HPLC (21%, white crystals). HPLC-MS m/z = 359.0 (M+1), Rt: 4.60.

& (200MHz ; CDCI3) : 3.44 (s, 3H), 4.73 (s, 2H), 7.20 (bd, 2H), 7.26-7. 48 (m, 6H), 7.92 (bd, 2H).

Example 32 (General procedure 3) Methyl-phenyl-carbamic acid 4- (4, 4-dimethyl-2, 6-dioxo-piperidin-1-yl)-phenyl ester The title product was prepared from 1- (4-hydroxyphenyl)-4, 4-dimethylpiperidine-2, 6-dione (233 mg, 1.00 mmol)) and 1-methyl-3-(methyl-phenyl-carbamoyl)-3H-imidazol-1-ium iodide (343 mg, 1.00 mmol) by applying general procedure 3 (192 mg, 52%, white solid). HPLC-MS m/z = 367 (M+1); Rt = 3.78 min.

1H NMR (300MHz, CDC13) : 61. 19 (s, 6H), 2.65 (s, 4H), 3.42 (s, 3H), 7.03 (d, 2H), 7.15-7. 43

(m, 7H).

Example 33 (General procedure 3) cis-Methyl-phenyl-carbamic acid 4- (1, 3-dioxo-octahydro-isoindol-2-yl)-phenyl ester The title compound (293 mg, 77% yield, white crystals) was prepared from cis-2- (4-hydroxy- phenyl) hexahydroisoindole-1, 3-dione (245 mg, 1.00 mmol) and 1-methyl-3- (methyl-phenyl-- carbamoyl)-3H-imidazol-1-ium iodide (343 mg, 1.00 mmol). HPLC-MS mlz = 379 (M+1); Rt = 4.08 min.

1H NMR (300MHz, CDC13) : 81. 50 (m, 4H), 1.90 (m, 4H), 3.00 (m, 1H), 3.42 (s, 3H), 7.13- 7.44 (m, 9H).

Example 34 (General procedure 3) Methyl-phenyl-carbamic acid 4- (cyclohexanecarbonyl-amino)-phenyl ester The title compound (283 mg, 80% yield, white crystals) was prepared from cyclohexanecar- boxylic acid (4-hydroxyphenyl) amide (219 mg, 1.00 mmol) and 1-methyl-3- (methyl-phenyl-- carbamoyl)-3H-imidazol-1-ium iodide (343 mg, 1.00 mmol). HPLC-MS m/z = 353 (M+1); Rt = 4.23 min.

'H NMR (300MHz, CDCI3) : a 1. 27 (m, 3H), 1.52 (m, 2H), 1.70 (m, 1 H), 1.76-1. 97 (m, 4H), 2.20 (m, 1H), 3.42 (s, 3H), 7.01 (d, 2H), 7.18 (d, 2H), 7.32-7. 50 (m, 7H).

Example 35 (General procedure 3) Methyl-phenyl-carbamic acid 4- (2-cyclohexyl-acetylamino)-phenyl ester The title compound (284 mg, 77% yield, white crystals) was prepared from 2-cyclohexyl-N- (4-hydroxy-phenyl)-acetamide (233 mg, 1.00 mmol) and 1-methyl-3- (methyl-phenyl-- carbamoyl)-3H-imidazol-1-ium iodide (343 mg, 1.00 mmol). HPLC-MS m/z = 367 (M+1); Rt = 4.51 min 'H NMR (300MHz, CDCI3) : 80. 87-1.03 (m, 2H), 1.07-1. 38 (m, 3H), 1. 60-1. 92 (m, 6H), 2.14 (d, 2H), 3.41 (s, 3H), 6.97 (d, 2H), 7.26 (m, 1H), 7.30-7. 44 (m, 6H), 7.55 (br. s, 1H, NH);.

Example 36 (General procedure 3) cis/trans-Methyl-phenyl-carbamic acid 4- [ (4-tert-butyl-cyclohexanecarbonyl)-amino]-phenyl ester

The title compound (353 mg, 86% yield, white crystals) was prepared from cis/trans-4-tert- butyl-cyclohexanecarboxylic acid (4-hydroxy-phenyl)-amide (275 mg, 1.00 mmol) and 1- methyl-3-(methyl-phenyl-carbamoyl)-3H-imidazol-1-ium iodide (343 mg, 1.00 mmol). HPLC- MS m/z = 409 (M+1); Rt = 5.28 and 5.42 min.

'H NMR (300MHz, CDCI3) : o5O. 82 + 0.86 (2 x s, 9H), 1.03 (m, 2H), 1.23-1. 70 (m, 4H), 1.82- 2.22 + 2.58 (m, 4H), 3.42 (s, 3H), 7.01 (m, 2H), 7.26 (m, 1 H), 7.31-7. 48 (m, 7H, arom. + NH).

Example 37 (General procedure 3) trans-Methyl-phenyl-carbamic acid 4- [ (4-tert-butyl-cyclohexanecarbonyl)-amino]-phenyl ester The title compound was obtained from cis/trans-4-tert-butyl-cyclohexanecarboxylic acid (4- hydroxy-phenyl)-amide by preparative HPLC (method B). Rt = 5.50 min.

'H NMR (300MHz, CDCI3) : 60. 85 (s, 9H), 1.03 (m, 3H), 1.52 (m, 2H), 1.88 (m, 2H), 2.01 (m, 2H), 2.12 (tt, J= 12.1, 3.3 Hz, 1H), 3.41 (s, 3H), 7.01 (br. d, 2H), 7.26 (m, 1H), 7.31-7. 48 (m, 7H, arom. + NH).

Example 38 (General procedure 3) cis-Methyl-phenyl-carbamic acid 4- [ (4-tert-butyl-cyclohexanecarbonyl)-amino]-phenyl ester The title compound was obtained from cis/trans-4-tert-butyl-cyclohexanecarboxylic acid (4- hydroxy-phenyl)-amide by preparative HPLC (method B). Rt = 6.34 min.

Example 39 (General procedure 3) Methyl-phenyl-carbamic acid 4- (3, 3-dimethyl-butyrylamino)-phenyl ester The title compound (262 mg, 77% yield) was prepared from N- (4-hydroxyphenyl)-3, 3- dimethyl-butyramide (275 mg, 1.00 mmol) and 1-methyl-3- (methyl-phenyl-carbamoyl)-3H- imidazol-1-ium iodide (343 mg, 1.00 mmol). HPLC-MS m/z = 341 (M+1); Rt = 4.15 min.

'H NMR (300MHz, CDCI3) : (51. 07 (s, 9H), 2.16 (s, 2H), 3.43 (s, 3H), 6.98 (d, 2H), 7. 26 (m, 1 H), 7.32-7. 43 (m, 6H), 7.51 (br. s, 1 H, NH).

Example 40 (General procedure 3) Methyl-phenyl-carbamic acid 3-(benzyl)-4-methyl-2-oxo-2H-chromen-7-yl ester

The title compound was prepared from 3-benzyl-7-hydroxy-4-methyl-2H-chromen-2-one and 3-(methyl-phenyl-carbamoyl)-1-methyl-3H-imidazol-1-ium iodide. HPLC-MS m/z = 400 (M+1), Rt: 4.90 min.

Example 41 (General procedure 3) Methyl-phenyl-carbamic acid 3- (3, 4-dichloro-benzyl)-4-methyl-2-oxo-2H-chromen-7-yl ester The title compound was prepared from 3- (3, 4-dichloro-benzyl)-7-hydroxy-4-methyl-2H- chromen-2-one and 3-(methyl-phenyl-carbamoyl)-1-methyl-3H-imidazol-1-ium iodide (white solid). HPLC-MS m/z = 468 (M+1), Rt: 5.47 min.

Example 42 (General procedure 3) Methyl-phenyl-carbamic acid 3- (2-chloro-6-fluoro-benzyl)-4-methyl-2-oxo-2H-chromen-7-yl ester The title compound was prepared from 3- (2-chloro-6-fluoro-benzyl)-7-hydroxy-4-methyl-2H- chromen-2-one and 3-(methyl-phenyl-carbamoyl)-1-methyl-3H-imidazol-1-ium iodide by ap- plying procedure 3. HPLC-MS m/z = 452 (M+1), Rt: 5.15 min.

Example 43 (General procedure 3) Methyl-phenyl-carbamic acid 3-(2, 6-dichloro-benzyl)-4-methyl-2-oxo-2H-chromen-7-yl ester The title compound was prepared from 3- (2, 6-dichloro-benzyl)-7-hydroxy-4-methyl-2H- chromen-2-one and 3-(methyl-phenyl-carbamoyl)-1-methyl-3H-imidazol-1-ium iodide. HPLC- MS m/z = 468 (M+1), Rt: 5.37 min.

Example 44 (General procedure 3) Methyl-phenyl-carbamic acid 3- (2, 6-dichloro-benzyl)-6-chloro-4-methyl-2-oxo-2H-chromen-7- yl ester The title compound was prepared from 3- (2, 6-dichloro-benzyl)-6-chloro-7-hydroxy-4-methyl- 2H-chromen-2-one and 3-(methyl-phenyl-carbamoyl)-1-methyl-3H-imidazol-1-ium iodide.

HPLC-MS m/z = 502 (M+1), Rt: 5.68 min.

Example 45 (General procedure 3)

Methyl-phenyl-carbamic acid 6-chloro-3- (2-chloro-6-fluoro-benzyl)-4-n-propy-2-oxo-2H- chromen-7-yl ester The title compound was prepared from 3- (4-fluoro-benzyl)-6-chloro-7-hydroxy-4-n-propyl-2H- chromen-2-one and 3-(methyl-phenyl-carbamoyl)-1-methyl-3H-imidazol-1-ium iodide. HPLC- MS m/z = 480 (M+1), Rt: 5.61 min.

Example 46 (General procedure 3) <BR> <BR> <BR> Methyl-phenyl-carbamic acid 3- (4-methoxy-phenyl)-4-methyl-2-oxo-2H-chromen-7-yl ester The title compound (90 mg, 43% yield, white solid) was prepared from 7-hydroxy-3- (4- methoxy-phenyl)-4-methyl-chromen-2-one (141 mg, 0.50 mmol) and 1-methyl-3- (methyl- phenyl-carbamoyl)-3H-imidazol-1-ium iodide (175 mg, 0.51 mmol).

'H NMR (300MHz, DMSO-d6) : 52. 28 (s, 3H), 3.38 (s, 3H), 3.80 (s, 3H), 7.00 (d, 2H), 7.18- 7.33 (m, 5H), 7.40-7. 53 (m, 4H), 7.83 (d, 1 H) ; HPLC-MS: m/z = 416 (M+1); Rt = 4.67 min.

Example 47 (General procedure 3) Methyl-phenyl-carbamic acid 4-methyl-2-oxo-3-phenyl-2H-chromen-7-yl ester The title compound (120 mg, 52% yield, white solid) was prepared from 7-hydroxy-4-methyl- 3-phenyl-chromen-2-one (126 mg, 0.50 mmol) and 1-methyl-3- (methyl-phenyl-carbamoyl)- 3H-imidazol-1-ium iodide (175 mg, 0.51 mmol).

'H NMR (300MHz, DMSO-d6) : 82. 26 (s, 3H), 3.37 (s, 3H), 7.16-7. 54 (m, 12H), 7.86 (d, 1H) ; HPLC-MS: m/z = 386 (M+1); Rt = 4.69 min.

Example 48 (General procedure 3) <BR> <BR> <BR> Methyl-phenyl-carbamic acid 3- (2, 5-dimethoxy-phenyl)-4-methyl-2-oxo-2H-chromen- 7-yl ester The title compound (30 mg, 13% yield, white solid) was prepared from 3- (2, 5-dimethoxy- phenyl)-7-hydroxy-4-methyl-chromen-2-one (156 mg, 0.50 mmol) and 1-methyl-3- (methyl- phenyl-carbamoyl)-3H-imidazol-1-ium iodide (175 mg, 0.51 mmol).

'H NMR (300MHz, CDC13) : 82. 21 (s, 3H), 3.45 (br. s, 3H), 3.72 (s, 3H), 3.79 (s, 3H), 6.74 (m, 1 H), 6.92 (m, 2H), 7.12 (br. s, 2H), 7.26-7. 46 (m, 5H), 7.63 (d, 1 H) ; HPLC-MS: m/z = 446

(M+1); Rt = 4.60 min.

Example 49 (General procedure 3) Methyl-phenyl-carbamic acid 3- (3, 4-dimethoxy-phenyl)-4-methyl-2-oxo-2H-chromen-7-yl es- ter.

The title compound (30 mg, 13% yield, oil) was prepared from 3- (3, 4-dimethoxy-phenyl)-7- hydroxy-4-methyl-chromen-2-one (156 mg, 0.50 mmol) and 1-methyl-3- (methyl-phenyl- carbamoyl)-3H-imidazol-1-ium iodide (175 mg, 0.51 mmol).

'H NMR (300MHz, CDCI3) : 82. 31 (s, 3H), 3.45 (br. s, 3H), 3. 89 (s, 3H), 4.02 (s, 3H), 6.83 (m, 2H), 6.94 (d, 1H), 7.12 (br. s, 2H), 7.27-7. 48 (m, 5H), 7.62 (d, 1H) ; HPLC-MS: m/z= 446 (M+1); Rt = 4.61 min.

Example 50 (General procedure 2) 4-Chlor-phenyl-methyl-carbamic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester The title compound was prepared from 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenol and 3 [ (4- chlorophenyl)-methyl-carbamoyl]-1-methyl-3H-imidazol-1-ium iodide. The crude product was subjected to flash chromatography (ethyl acetate/heptan, 1: 5) (77%, white crystals). HPLC- MS m/z = 423.1 (M+1), Rt: 5.3 min.

AH (300MHz ; CDCl3) : 3.42 (s, 3H), 6.99 (d, 1H, J 8.7), 7.10-7. 20 (m, 4H), 7.30 (d, 2H, J 8.3), 7.37 (d, 2H, J 8.6), 7.88 (dd, 1 H, J 8.7 and 2.2), 8.42 bs, 1 H).

Example 51 (General procedure 2) 4-Chlor-phenyl-methyl-carbamic acid 4- (3, 5-dichloro-pyridin-2-yloxy)-phenyl ester The title compound was prepared from 4- (3, 5-dichloro-pyridin-2-yloxy)-phenol and 3- [ (4- chlorophenyl)-methyl-carbamoyl]-1-methyl-3H-imidazol-1-ium iodide. The crude product was subjected to flash chromatography (Quad flash 12, dichlormethane (67%). HPLC-MS m/z = 422.9 (M+1), Rt: 5.5 min.

AH (300MHz ; CDCI3) : 3.41 (s, 3H), 7.20-7. 08 (m, 4H), 7.29 (d, 2H, J 9), 7.37 (dd, 2H, J 6.4 and 2. 2), 7.76 (d, 1 H, J 2. 3), 7.93 (d, 1 H, J 2. 3).

Example 52 (General procedure 2) (4-Chloro-phenyl)-methyl-carbamic acid 4- (2-cyano-5-trifluoromethyl-pyridin-3-yloxy)-phenyl

ester The title compound was prepared from 4- (2-cyano-5-trifluoromethyl-pyridin-3-yloxy)-phenol and 3- [ (4-chlorophenyl)-methyl-carbamoyl]-1-methyl-3H-imidazol-1-iu m iodide. The crude product was purified by preparative HPLC (25%). HPLC-MS m/z = 448.2 (M+1), Rt: 5.1 min. i (300MHz ; CDCI3) : 3.43 (s, 3H), 7.12 (d, 2H, J 9.0), 7.19-7. 35 (m, 4H), 7.39 (dd, 2H, J 6.6 and 1.8), 7.36-7. 41 (m, 1 H), 8.63 (d, 1 H, J 0.7).

Example 53 (General procedure 1) Ethyl-phenyl-carbamic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester The title compound was prepared from 4- (4-trifluoromethyl-pyridin-2-yloxy)-phenol and N- ethyl-N-phenylcarbamoyl chloride. The crude product was subjected to flash chromatography (ethyl acetate/heptane, 1: 5) (78%, white crystals). HPLC-MS m/z = 403.2 (M+1), Rt: 5.17 min. i (300MHz ; CDCI3) : 1.25 (t, 3H, J 6.8), 3.83 (q, 2H, J 6.8), 6.98 (d, 1H, J 8.6), 7.12 (m, 4H), 7.32 (d, 2H, J 7.1), 7.32 (m, 1H), 7.41 (t, 2H, J 7.5), 7.87 (dt, 1H, J 8.7 and 2.7), 8.42 (bs, 1H).

Example 54 (General procedure 1) Ethyl-phenyl-carbamic acid 4- (4-trifluoromethyl-phenoxy)-phenyl ester The title compound was prepared from 4- (4-trifluoromethyl-phenoxy)-phenol and N-ethyl-N- phenylcarbamoyl chloride. The crude product was subjected to flash chromatography (ethyl acetate/heptane, 1: 5) (77%, white crystals. HPLC-MS m/z = 402.1 (M+1), Rt: 5.6 min. i (300MHz ; CDCI3) : 1.25 (t, 3H, J 7.2), 3.83 (q, 2H, J 7.2), 7.01 (d, 4H, J 8.6) 7.12 (d, 2H, J 8. 3), 7.30 (t, 2H, J 6. 8), 7.30 (m, 1H), 7.42 (dt, 2H, J 7. 5), 7.54 (d, 2H, J 8. 6) Example 55 (General procedure 2) Benzyl-methyl-carbamic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester The title compound was prepared from 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenol and 3- (benzyl-methyl-carbamoyl)-1-methyl-3H-imidazol-1-ium iodide. The crude product was sub- jected to flash chromatography (ethyl acetate/heptane, (1: 5) (69%, colourless oil) HPLC-MS m/z = 403.2 (M+1), Rt: 5. 11 min

i (300MHz ; CDCI3) : 3.03 (d, 3H, J 8.0), 4.64 (d, 2H, J 24.9), 7.00 (d, 1H), 7.10-7. 26 (m, 4H), 7.30-7. 50 (m, 5H), 7.88 (dd, 1 H), 8.43 (s, 1 H).

Example 56 (General procedure 2) Benzyl-methyl-carbamic acid 4- (3, 5-dichloro pyridin-2-yloxy)-phenyl ester The title compound was prepared from 4- (3, 5-dichloro pyridin-2-yloxy)-phenol and 3-(benzyl- methyl-carbamoyl)-1-methyl-3H-imidazol-1-ium iodide.

The crude product was subjected to flash chromatography (Quad flash 12, dichloromethane) (92%, oil). HPLC-MS m/z = 403.2 (M+1), Rt: 5.4 min.

8H (300MHz ; CDCI3) : 3.02 (d, 3H, J 7.2), 4.60 (d, 2H, J 24.1), 7.05-7. 25 (m, 4H), 7.28-7. 45 (m, 5H), 7.76 (d, 1H, J 2. 3) 7.95 (d, 1H, J J 2. 2).

Example 57 (General procedure 2) tert-Butyl-methyl-carbamic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester The title compound was prepared from 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenol and 3- (tert-Butyl-methyl-carbamoyl)-1-methyl-3H-imidazol-1-ium iodide. The crude product was subjected to preparative HPLC (34%, white crystals). HPLC-MS m/z = 369.1 (M+1), Rt: 5.17 min.

4s (300MHz ; CDCI3) : 1. 47 (s, 9H), 3.08 (s, 3H), 6.99 (d, 1 H), 7.09-7. 20 (m, 4H), 7.87 (dd, 1 H), 8. 43 (bs, 1 H).

Example 58 (General procedure 2) Isopropyl-methyl-carbamic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester The title compound was prepared from 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenol and 3- (isopropyl-methyl-carbamoyl)-1-methyl-3H-imidazol-1-ium iodide. The crude product was subjected to flash chromatography (ethyl acetate/heptane 1: 5) (77%, white crystals). HPLC- MS m/z = 355.1 (M+1), Rt: 4.80 min. i (300MHz ; CDC13) : 1.21 (m, 6H), 2.91 (d, 3H), 4.49 (qi, 1H), 6.99 (d, 1H), 7.10-7. 25 (m, 4H) 7.88 (dd, 1 H), 8. 44 (s, 1 H).

Example 59 (General procedure 2) Cyclohexyl-methyl-carbamic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester.

The title compound was prepared from 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenol and 3- (cyclohexyl-methyl-carbamoyl)-1-methyl-3H-imidazo--1-ium iodide. The crude product was subjected to flash chromatography (ethyl acetate/heptane, 1: 5) (80%, white crystals). HPLC- MS m/z = 395.2 (M+1), Rt: 5.7 min.

& (300MHz ; CDCI3) : 1.13 (m, 1H), 1.50-1. 30 (m, 4H), 1.68 (d, 1H, J 13.2), 1.75-1. 95 (m, 4H), 2.93 (d, 2H, J 12.1), 2.90-3. 00 (m, 1H), 4.02 (t, 1 H, J 12. 1), 6.99 (d, 1 H, J 8. 7), 7.10-7. 17 (, 4H), 7.88 (dd, 1 H, J 8. 7 and 2.3), 8.44 (s, 1 H).

Example 60 (General procedure 1) Dimethyl-carbamic acid 4- (3, 5-dichloro pyridin-2-yloxy)-phenyl ester The title compound was prepared from 4- (3, 5-dichloro pyridin-2-yloxy)-phenol and dimethyl- carbamoyl chloride. The crude product was purified by preparative HPLC (38%). HPLC-MS m/z = 327.0 (M+1), Rt: 4.7 min.

#H (300MHz ; CDCI3) : 2.92 (s, 3H), 3.05 (s, 3H), 7.10-7. 25 (m, 4H), 8.17 (d, 1H), 8.34 (d, 1H).

Example 61 (General procedure 1) Pyrrolidine1-carboxylic acid 4- (3, 5-dichloro-pyridin-2-yloxy)-phenyl ester The title compound was prepared from 4- (3, 5-dichloro-pyridine-2-yloxy)-phenol and 1- pyrrolidinecarbamoyl chloride. The crude product was purified by preparative HPLC (64%, white crystals). HPLC-MS m/z = 353.0 (M+1), Rt: 5.00 min. c'H (300MHz ; CDCI3) : 1.95 (qi, 4H, J 6.4), 3.48 (t, 2H, J 6.4), 3.56 (t, 2H, 6.4), 7.10 (t, 1H, J 2.7), 7.13 (t, 1H, J 2. 7), 7.17 (t, 1H, J 2.0), 7.20 (t, 1H, J 2. 3), 7.76 (d, 1H, J 2. 6), 7.95 (d, 1H J, 2.6).

Example 62 (General procedure 2) 2, 3-Dihydro-indole-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester.

The title compound was prepared from 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenol and 3- (2, 3-dihydro-indole-1-carbonyl)-1-methyl-3H-imidazol-1-ium iodide. The crude product was subjected to column chromatography (ethyl acetate/heptane, 1: 5) (73%, crystals. HPLC-MS m/z = 401.1) (M+1), Rt: 5.5 min. i (300MHz ; CDCl3) : 3.24 (t, 2H, J 8. 4), 4.25 (t, 2H, J 8.4), 7.10 (m, 2H), 7.15-7. 35 (m, 6H),

7.90 (dd, 2H, J 8.7 and 2.6), 8.44 (bs, 1 H).

Example 63 (General procedure 2) 1, 3-Dihydro-isoindole-2-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester.

The title compound was prepared from 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenol and 3- (1, 3-dihydro-isoindole-2-carbonyl)-1-methyl-3H-imidazol-1-ium iodide. The crude product was recrystallized (ethanol) (&num 100). HPLC-MS m/z = 401.1 (M+1), Rt: 5.1 min. i (300MHz ; CDCI3) : 4.85 (s, 2H), 4.95 (s, 2H), 7.01 (d, 1H, J 8.69), 7.16 (dt, 2H, J 9.4 and 2.7), 7.22-7. 29 (m, 2H), 7.30-7. 35 (m, 4H), 7.89 (dd, 1 H, J 8.6 and 3.0), 8.45 (m, 1 H).

Example 64 (General procedure 2) Piperidine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester The title compound was prepared from 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenol and 1- methyl-3- (piperidine-1-carbonyl)-3H-imidazol-1-ium iodide. The crude product was recrystal- lized (ethanol) (45%). HPLC-MS m/z = 367.02 (M+1), Rt: 4.9 min.

4i (30OMHz ; CDCI3) : 1.65 (bs, 6H), 3.58 (d, 4H, J 21.4), 6.99 (d, 1H, J 8.7), 7.10-7. 24 (m, 4H), 7.88 (dd, 1 H, J 8. 7 and 2.2), 8.44 (bs, 1 H).

Example 65 (General procedure 2) 2-Methyl-piperidine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester The title compound was prepared from 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenol and 1- methyl-3- (2-methyl-piperidine-1-carbonyl)-3H-imidazol-1-ium iodide. The crude product was purified by flash chromatography using a Quad flash 25 (ethyl acetate/heptane (1: 6), (71%, white crystals). HPLC-MS m/z = 381.1 (M+1), Rt: 5.2 min.

9H (300MHz ; CDCI3) : 1.26 (d, 3H), 1.40-1. 85 (m, 6H), 3.03 (t, 1 H), 4.11 (dd, 1 H), 4.50-4. 65 (m, 1H), 6.95-7. 02 (d, 1H), 7.10-7. 20 m, 4H), 7.88 (dd, 1H), 8.43 (bs, 1H).

Example 66 (General procedure 2) 3-Methyl-piperidine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester The title compound was prepared from 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenol and 1- methyl-3- (3-methyl-piperidine-1-carbonyl)-3H-imidazol-1-ium iodide. The crude product was

purified by flash chromatography using a Quad flash 25 (ethyl acetate/heptane (1: 6), (75%, white crystals). HPLC-MS m/z = 381.1 (M+1), Rt: 5.4 min.

SH (300MHz ; CDCI3) : 0.94 (d, 3H), 1.05-1. 20 (m, 1 H), 1.50-1. 80 (m, 3H), 1.80-1. 95 (m, 1 H), 2.45-2. 75 (dt, 1H), 2.80-3. 00 (m, 1H), 4.00-4. 25 (m, 2H), 6.95-7. 05 (d, 1H), 7.10-7. 25 (m, 4H), 7.88 (dd, 1 H), 8.43 (bs, 1H).

Example 67 (General procedure 2) 4-Methyl-piperidine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester The title compound was prepared from 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenol and 1- methyl-3- (4-methyl-piperidine-1-carbonyl)-3H-imidazol-1-ium iodide. The crude product was purified by flash chromatography using a Quad flash 25 (ethyl acetate/heptane (1: 6), (73%, white crystals). HPLC-MS m/z = 381.1 (M+1), Rt: 5.4 min.

8H (300MHz ; CDCI3) : 1.00 (d, 3H), 1.23 (dq, 2H), 1.52-1. 65 (m, 1 H), 1.70 (d, 2H), 2.75-3. 05 (m, 2H), 4.15-4. 35 (m, 2H), 6.99 (d, 1H), 7.05-7. 20 (m, 4H), 7.88 (dd, 1H), 8.43 (s, 1H).

Example 68 (General procedure 2) 4-Benzyl-piperidine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester The title compound was prepared from 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenol and 1- methyl-3- (4-benzyl-piperidine-1-carbonyl)-3H-imidazol-1-ium iodide. The crude product was purified by flash chromatography using a Quad flash 25 (ethyl acetate/heptane (1: 6), (72%, white crystals). HPLC-MS m/z = 457.2 (M+1), Rt: 6.0 min.

& (300MHz ; CDCI3) : 1.20-1. 40 (m, 2H), 1.65-1. 85 (m, 3H), 2.59 (d, 2H), 2.70-3. 00 (m, 2H), 4.15-4. 35 (m, 2H), 6.99 (d, 1H), 7.05-7. 22 (m, 6H), 7.22-7. 35 (m, 3H), 7. 88 (dd, 1H), 8.43 (bs, 1 H).

Example 69 (General procedure 2) 3, 4-Dihydro-1 H-isoquinoline-2-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl es- ter The title compound was prepared from 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenol and 3- (3, 4-dihydro-1 H-isoquinoline-2-carbonyl)-1-methyl-3H-imidazol-1-ium iodide. The crude pro- duct was recrystallized (ethanol) (53%). HPLC-MS m/z = 415.2 (M+1), Rt: 5.3 min.

& (300MHz ; CDC13) : 2.96 (d, 2H, J 4.9), 3.86 (dt, 2H, J 23.3 and 6.0), 4.79 (d, 2H, J 35.4),

7.00 (d, 1H, J 8.7), 7.10-7. 23 (m, 8H), 7.88 (dt, 1H, J 8.7 and 2.1), 8.44 (s, 1H).

Example 70 (General procedure 2) 3, 4-Dihydro-2H-quinoline-1-carboxylic acid 4- (3, 5-dichloro-pyridin-2-yloxy)-phenyl ester The title compound was prepared from 4- (3, 5-dichloro-pyridin-2-yloxy)-phenol and 3- (3, 4- dihydro-2H-quinoline-1-carbonyl)-1-methyl-3H-imidazol-1-ium iodide. The crude product was recrystallized (ethanol) (68%). HPLC-MS m/z = 415.2 (M+1), Rt: 5.6 min.

#H (300MHz ; CDCI3) : 2.05 (Qi, 2H, J 6. 8), 2.85 (t, 2H, J 6.8), 3.92 (t, 2H, J 6.8), 7.06 (dt, (1 H, J 7. 4 and 1.1), 7,11-7. 19 (m, 4H), 7.21 (t, 1H, J 2.8), 7.24 (t, 1H, J 2.7), 7.77 (d, 1H, J 2.3), 7.75-7. 80 (m, 1 H), 7.95 (d, 1 H, J 2.39).

Example 71 (General procedure 2) 3, 4-Dihydro-2H-quinoline-1-carboxylic acid 4- (2-cyano-5-trifluoromethyl-pyridin-3- yloxy)-phenyl ester The title compound was prepared from 4- (2-cyano-5-trifluoromethyl-pyridin-3-yloxy)-phenol and 3- (3, 4-dihydro-2H-quinoline-1-carbonyl)-1-methyl-3H-imidazol-1-iu m iodide. The crude product was subjected to flash chromatography (Quad flash 12, dichlormethane) (43%, oil).

HPLC-MS m/z = 440.2 (M+1), Rt: 5.2 min.

#H (300MHz ; CDCl3) : 2.07 (Qi, 2H, J 6.4), 2.87 (t, 2H, J 6.4), 3.94 (t, 2H, J 6.4), 7.25-7. 04 m, 5H), 7.26-7. 7.36 (m, 2H), 7.44 (d, 1 H, J 1.5), 7.76 (bd, 1 H, J 7.2), 8. 64 (s, 1 H).

Example 72 (General procedure 3) 3, 4-Dihydro-2H-quinoline-1-carboxylic acid 3- (3, 4-dichloro-benzyl)-4-methyl-2-oxo-2H- chromen-7-yl ester The title compound was prepared from 3- (3, 4-dichloro-benzyl)-7-hydroxy-4-methyl-2H- chromen-2-one and 3- (3, 4-dihydro-2H-quinoline-1-carbonyl)-1-methyl-3H-imidazol-1-iu m io- dide. HPLC-MS m/z = 494 (M+1), Rt: 5.86 min.

Example 73 (General procedure 3) 3, 4-Dihydro-2H-quinoline-1-carboxylic acid 3-benzyl-4-methyl-2-oxo-2H-chromen-7-yl ester The title compound was prepared from 3-benzyl-7-hydroxy-4-methyl-2H-chromen-2-one and

3- (3, 4-dihydro-2H-quinoline-1-carbonyl)-1-methyl-3H-imidazol-1-iu m iodide. HPLC-MS m/z = 426 (M+1), Rt: 5.34 min.

Example 74 (General procedure 3) 3, 4-Dihydro-2H-quinoline-1-carboxylic acid 3- (2-chloro-6-fluoro-benzyl)-4-methyl-2-oxo-2H- chromen-7-yl ester The title compound was prepared from 3- (2-chloro-6-fluoro-benzyl)-7-hydroxy-4-methyl-2H- chromen-2-one and 3- (3, 4-dihydro-2H-quinoline-1-carbonyl)-1-methyl-3H-imidazol-1-iu m io- dide. HPLC-MS m/z = 478 (M+1), Rt: 5.58 min.

Example 75 (General procedure 3) 3, 4-Dihydro-2H-quinoline-1-carboxylic acid 3- (2, 6-dichloro-benzyl)-4-methyl-2-oxo-2H- chromen-7-yl ester The title compound was prepared from 3- (2, 6-dichloro-benzyl)-7-hydroxy-4-methyl-2H- chromen-2-one and 3- (3, 4-dihydro-2H-quinoline-1-carbonyl)-1-methyl-3H-imidazol-1-iu m io- dide. HPLC-MS m/z = 494 (M+1), Rt: 5.79 min.

Example 76 (General procedure 3) 3, 4-Dihydro-2H-quinoline-1-carboxylic acid 3- (2, 6-dichloro-benzyl)-6-chloro-4-methyl-2-oxo- 2H-chromen-7-yl ester The title compound was prepared from 3- (2, 6-dichloro-benzyl)-6-chloro-7-hydroxy-4-methyl- 2H-chromen-2-one and 3- (3, 4-dihydro-2H-quinoline-1-carbonyl)-1-methyl-3H-imidazol-1-iu m iodide. HPLC-MS m/z = 530 (M+1), Rt: 6.09 min.

Example 77 (General procedure 3) 3, 4-Dihydro-2H-quinoline-1-carboxylic acid 3- (4-fluoro-benzyl)-4-methyl-2-oxo-2H-chromen- 7-yl ester The title compound was prepared from 3- (4-fluoro-benzyl)-7-hydroxy-4-methyl-2H-chromen- 2-one and 3- (3, 4-dihydro-2H-quinoline-1-carbonyl)-1-methyl-3H-imidazol-1-iu m iodide.

HPLC-MS m/z = 444 (M+1), Rt: 5.36 min.

Example 78 (General procedure 3) 3, 4-Dihydro-2H-quinoline-1-carboxylic acid 6-chloro-3- (2-chloro-6-fluoro-benzyl)-4-n-propy-2- oxo-2H-chromen-7-yl ester The title compound was prepared from 3- (4-fluoro-benzyl)-6-chloro-7-hydroxy-4-n-propyl-2H- chromen-2-one and 3- (3, 4-dihydro-2H-quinoline-l-carbonyl)-l-methyl-3H-imidazol-l-iu m io- dide. HPLC-MS m/z = 506 (M+1), Rt: 6.01 min.

Example 79 (General procedure 3) 3, 4-Dihydro-2H-quinoline-1-carboxylic acid 3- (4-methoxy-phenyl)-4-methyl-2-oxo-2H- chromen-7-yl ester The title compound (130 mg, 59% yield, white solid) was prepared from 7-hydroxy-3- (4- methoxy-phenyl)-4-methyl-chromen-2-one (141 mg, 0.50 mmol) and 3- (3, 4-dihydro-2H- quinoline-1-carbonyl)-1-methyl-3H-imidazol-1-ium iodide (188 mg, 0.51 mmol).

'H NMR (300MHz, DMSO-d6) : 52. 00 (quintet, 2H), 2.30 (s, 3H), 2.82 (t, 2H), 3.81 (s, 3H), 3.88 (t, 2H), 7.02 (d, 2H), 7.08 (m, 1H), 7.19 (m, 2H), 7.27 (d, 2H), 7.31 (dd, 1H), 7.41 (d, 1H), 7.72 (d, 1H), 7.88 (d, 1H) ; HPLC-MS: m/z = 442 (M+1); Rt = 5.13 min.

Example 80 (General procedure 3) 3, 4-Dihydro-2H-quinoline-1-carboxylic acid 4-methyl-2-oxo-3-phenyl-2H-chromen-7-yl ester The title compound (150 mg, 73% yield, white solid) was prepared from 7-hydroxy-4-methyl- 3-phenyl-chromen-2-one (126 mg, 0.50 mmol) and 3-(3,4-dihydro-2H-quinoline-1-carbonyl)- 1-methyl-3H-imidazol-1-ium iodide (188 mg, 0.51 mmol).

'H NMR (300MHz, DMSO-d6) : 61. 99 (quintet, 2H), 2.28 (s, 3H), 2.82 (t, 2H), 3. 88 (t, 2H), 7.08 (m, 1H), 9.19 (m, 2H), 7.33 (m, 3H), 7.46 (m, 4H), 7.74 (d, 1H), 7.90 (d, 1H) ; HPLC-MS : m/z = 412 (M+1); Rt = 5.14 min.

Example 81 (General procedure 3) 3, 4-Dihydro-2H-quinoline-1-carboxylic acid 3-(2, 5-dimethoxy-phenyl)-4-methyl-2-oxo-2H- chromen-7-yl ester The title compound (50 mg, 21 % yield, white solid) was prepared from 3- (2, 5-dimethoxy- phenyl)-7-hydroxy-4-methyl-chromen-2-one (156 mg, 0.50 mmol) and 3- (3, 4-dihydro-2H-

quinoline-1-carbonyl)-1-methyl-3H-imidazol-1-ium iodide (188 mg, 0.51 mmol).

1H NMR (300MHz, CDCI3) : 92. 08 (quintet, 2H), 2.34 (s, 3H), 2.87 (t, 2H), 3.73 (s, 3H), 3.80 (s, 3H), 3.94 (t, 2H), 6.74 (m, 1 H), 6.93 (m, 2H), 7.07-7. 26 (m, 5H), 7.68 (d, 1H), 7.77 (br. d, 1 H) ; HPLC-MS: m/z = 472 (M+1); Rt = 5.04 min.

Example 82 (General procedure 3 3, 4-Dihydro-2H-quinoline-1-carboxylic acid 3- (3, 4-dimethoxy-phenyl)-4-methyl-2-oxo-2H- chromen-7-yl ester The title compound (50 mg, 21% yield, oil) was prepared from 3- (3, 4-dimethoxy-phenyl)-7- hydroxy-4-methyl-chromen-2-one (156 mg, 0.50 mmol) and 3- (3, 4-dihydro-2H-quinoline-1- carbonyl)-1-methyl-3H-imidazol-1-ium iodide (188 mg, 0.51 mmol).

'H NMR (300MHz, CDCI3) : 82. 08 (quintet, 2H), 2.33 (s, 3H), 2.88 (t, 2H), 3.89 (s, 3H), 4.03 (s, 3H), 4.06 (t, 2H), 6.65 (m, 2H), 6.96 (d, 1 H), 7.05-7. 25 (m, 5H), 7.68 (d, 1 H), 7.77 (br. d, 1 H) ; HPLC-MS: m/z = 472 (M+1); Rt = 5.14 min.

Example 83 (General procedure 2) 7-Trifluoromethyl-3, 4-dihydro-2H-quinoline-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2- yloxy)-phenyl ester.

The title compound was prepared from 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenol and 1- methyl-3- (7-trifluoromethyl-3, 4-dihydro-2H-quinoline-1-carbonyl)-3H-imidazol-1-ium iodide.

The crude product was subjected to preparative HPLC (66 %). HPLC-MS m/z: 483.1 (M+1), Rt: 5.87 min. i (200MHz; CDCI3) : 2.08 (Qi, 2H), 2.90 (t, 2H), 3.98 (t, 2H), 7.03 (d, 1H), 7.1-7. 40 (m, 6H), 7.90 (dd, 1H), 8.18 (s, 1H), 8.44 (d, 1H).

Example 84 (General procedure 1) Morpholine-4-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester The title compound was prepared from 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenol and mor- pholine-4-carbonyl chloride. The crude product was purified by preparative HPLC (37%, white crystals). HPLC-MS m/z = 369.1 (M+1), Rt: 4.3 min.

& (300MHz ; CDCI3) : 3.59 (bs, 2H), 3.67 (bs, 2H), 3.76 (m, 4H), 7.01 (d, 1H, J 8.7), 7.12-7. 18 (m, 2H), 7.16 (d, 2H, J 3.7), 7.90 (dd, 1H, J 8. 7 and 2.6), 8.43 (s, 1H).

Example 85 (General procedure 1) Morpholine-4-carboxylic acid 4- (3, 5-dichloro-pyridin-4-yloxy)-phenyl ester The title compound was prepared from 4- (3, 5-dichloro-pyridin-4-yloxy)-phenol and mor- pholine-4-carbonyl chloride. The crude product was purified by preparative HPLC (66%, white crystals. HPLC-MS m/z = 368.9 (M+1), Rt: 4.0 min. i (300MHz ; CDCI3) : 3.57 (bs, 2H), 3.65 (bs, 2H) 3.74 (m, 4H), 6.83 (d, 1 H, J 9), 6.83 (m, 1 H) 7.08 (d, 1 H, J 9), 7.08 (m, 1 H), 8.56 (s, 2H).

Example 86 (General procedure 1) Morpholine-4-carboxylic acid 4- (4-trifluoromethyl-phenoxy)-phenyl ester The title compound was prepared from 4- (4-trifluoromethyl-phenoxy)-phenol and morpholine- 4-carbonyl chloride. The crude product was purified by preparative HPLC (74%, white crys- tals). HPLC-MS m/z = 368.1 (M+1), Rt: 4.85 min.

& (300MHz ; CDCI3) : 3.59 (bs, 2H), 3. 68 (bs, 2H), 3.75 (m, 4H), 7.04 (d, 2H, J 6.4), 7.04 (m, 2H), 7.14 (d, 1 H, J 9), 7.13 (m, 1H), 7.57 (d, 2H, J 8. 3).

Example 87 (General procedure 1) Morpholine-4-carboxylic acid 4-tert-butoxy-phenyl ester The title compound was prepared from 4- (tert-butoxy)-phenol and 4-morpholine-carbamoyl chloride. The crude product was recrystallized (ethanol) (69%, crystals) ; mp: 128. 8-129. 5°C.

HPLC-MS m/z = 280.1 (M+1), Rt: 3.6 min.

4 {(300MHz ; CDCI3) : 1.33 (s, 9H, ), 3. 58 (bs, 2H), 3.66 (bs, 2H), 6.8-7. 1 (m, 4H) Example 88 (General procedure 1) Morpholine-4-carboxylic acid 4- (3, 5-dichloro-pyridin-2-yloxy)-phenyl ester The title compound was prepared from 4- (3, 5-dichloro-pyridin-2-yloxy)-phenol and mor- pholine-4-carbonyl chloride. The crude product was purified by preparative HPLC (45%, crys- tals. HPLC-MS m/z = 369.1 (M+1), Rt: 4.3 min.

Example 89 (General procedure 1)

Morpholine-4-carboxylic acid 3- (4-fluoro-benzyl)-4-methyl-2-oxo-2H-chromen-7-yl ester The title compound was prepared from 3- (4-fluorobenzyl)-7-hydroxy-4-methyl-2H-chromen-2- one and morpholine-4-carbonyl chloride. The crude product was recrystallized (ethanol) (78%, crystals). HPLC-MS m/z = 398.0 (M+1), Rt: 4.3 min. i (200MHz ; DMSO-d) : 2.47 (s, 3H), 3.45 (bs, 2H), 3.56-3. 72 (m, 6H), 3.96 (s, 2H), 7.08 (t, 2H), 7.16-7. 35 (m, 4H, 7.83 (d, 1H).

Example 90 (General procedure 1) Morpholine-4-carboxylic acid 4- (5, 7-bis-trifluoromethyl- [1, 8] naphthypyridin-2-yloxy)-phenyl ester The title compound was prepared from 4- (5, 7-bis-trifluoromethyl- [1, 8] naphthypyridin-2-yloxy)- phenol and morpholine-4-carbonyl chloride. The crude product was tested without purifica- tion ( 100%). HPLC-MS m/z = 488.0 (M+1), Rt: 5.0 min.

Example 91 (General procedure 3) Morpholine-4-carboxylic acid 3- (3, 4-dichloro-benzyl)-4-methyl-2-oxo-2H-chromen-7-yl ester The title compound was prepared from 3- (3, 4-dichloro-benzyl)-7-hydroxy-4-methyl-2H- chromen-2-one and 3-(morpholine-4-carbonyl)-1-methyl-3H-imidazol-1-ium iodide. HPLC-MS m/z = 448 (M+1), Rt: 4.73 min.

Example 92 (General procedure 3) Morpholine-4-carbamic acid 3-(benzyl)-4-methyl-2-oxo-2H-chromen-7-yl ester The title compound was prepared from 3- (benzyl)-7-hydroxy-4-methyl-2H-chromen-2-one and 1-methyl-3-(morpholine-4-carbonyl)-3H-imidazol-1-ium iodide. HPLC-MS m/z = 380 (M+1), Rt: 4.05 min.

Example 93 (General procedure 3) Morpholine-4-carbamic acid 3-(2-chloro-6-fluoro-benzyl)-4-methyl-2-oxo-2H-chromen-7-yl ester

The title compound was prepared from 3-(2-chloro-6-fluoro-benzyl)-7-hydroxy-4-methyl-2H- chromen-2-one and 1-methyl-3-(morpholine-4-carbonyl)-3H-imidazol-1-ium iodide. HPLC-MS m/z = 432 (M+1), Rt: 4.36 min.

Example 94 (General procedure 3) Morpholine-4-carbamic acid 3-(2, 6-dichloro-benzyl)-4-methyl-2-oxo-2H-chromen-7-yl ester The title compound was prepared from 3- (2, 6-dichloro-benzyl)-7-hydroxy-4-methyl-2H- chromen-2-one and 1-methyl-3-(morpholine-4-carbonyl)-3H-imidazol-1-ium iodide. HPLC-MS m/z = 448 (M+1), Rt: 4.59 min.

Example 95 (General procedure 3) Morpholine-4-carbamic acid 3-(2, 6-dichloro-benzyl)-4-methyl-2-oxo-2H-chromen-7-yl ester The title compound was prepared from 3-(2, 6-dichloro-benzyl)-6-chloro-7-hydroxy-4-methyl- 2H-chromen-2-one and 1-methyl-3-(morpholine-4-carbonyl)-3H-imidazol-1-ium iodide.

HPLC-MS m/z = 484 (M+1), Rt: 4.99 min.

Example 96 (General procedure 3) Morpholine-4-carbamic acid 3- (4-fluoro-benzyl)-4-methyl-2-oxo-2H-chromen-7-yl ester The title compound was prepared from 3- (4-fluoro-benzyl)-7-hydroxy-4-methyl-2H-chromen- 2-one and 1-methyl-3- (morpholine-4-carbonyl)-3H-imidazol-1-ium iodide. HPLC-MS m/z = 398 (M+1), Rt: 4.12 min.

Example 97 (General procedure 3) Morpholine-4-carbamic acid 6-chloro-3- (2, 6-dichloro-benzyl)-4-n-propy-2-oxo-2H-chromen-7- yl ester The title compound was prepared from 3- (4-fluoro-benzyl)-6-chloro-7-hydroxy-4-n-propyl-2H- chromen-2-one and 1-methyl-3-(morpholine-4-carbonyl)-3H-imidazol-1-ium iodide. HPLC-MS m/z = 460 (M+1), Rt: 4.90 min.

Example 98 (General procedure 3) Morpholine-4-carboxylic acid 4-methyl-2-oxo-3-phenyl-2H-chromen-7-yl ester

The title compound (75 mg, 41 % yield, crystals) was prepared from 7-hydroxy-4-methyl-3- phenyl-chromen-2-one (126 mg, 0.50 mmol) and 1-methyl-3- (morpholine-4-carbonyl)-3H- imidazol-1-ium iodide (165 mg, 0.51 mmol).

'H NMR (300MHz, CDCI3) : 82. 27 (s, 3H), 3.45 (br. s, 2H), 3.62 (br. s, 2H), 3.68 (m, 4H), 7.23 (dd, 1 H), 7.32 (m, 3H), 7.43 (m, 3H), 7.87 (d, 1 H) ; HPLC-MS: m/z = 366 (M+1); Rt = 3. 79 min.

Example 99 (General procedure 3) <BR> <BR> <BR> Morpholine-4-carboxylic acid 3- (4-methoxy-phenyl)-4-methyl-2-oxo-2H-chromen-7-yl ester The title compound (120 mg, 61 % yield, crystals) was prepared from 7-hydroxy-3- (4- methoxy-phenyl)-4-methyl-chromen-2-one (141 mg, 0.50 mmol) and 1-methyl-3- (morpholine- 4-carbonyl)-3H-imidazol-1-ium iodide (165 mg, 0.51 mmol).

'H NMR (300MHz, DMSO-d6) : 62. 29 (s, 3H), 3.43 (br. s, 2H), 3.61 (br. s, 2H), 3.66 (m, 4H), 3.81 (s, 3H), 7.01 (d, 2H), 7.20-7. 30 (m, 4H), 7.84 (d, 1 H) ; HPLC-MS: m/z = 396 (M+1); Rt = 3. 80 min.

Example 100 (General procedure 3) Morpholine-4-carboxylic acid 3- (3, 4-dimethoxy-phenyl)-4-methyl-2-oxo-2H-chromen-7-yl es- ter The title compound (120 mg, 56% yield) was prepared from 3- (3, 4-dimethoxy-phenyl)-7- hydroxy-4-methyl-chromen-2-one (156 mg, 0.50 mmol) and 1-methyl-3- (morpholine-4- carbonyl)-3H-imidazol-1-ium iodide (165 mg, 0.51 mmol).

'H NMR (300MHz, DMSO-d6) : 82. 29 (s, 3H), 3.46 (br. s, 2H), 3.62 (br. s, 2H), 3.67 (m, 4H), 3.74 (s, 3H), 3.81 (s, 3H), 6.83 (dd, 1H), 6.92 (d, 1 H), 7.02 (d, 1H), 7.22 (dd, 1 H), 7.30 (d, 1 H), 7.85 (d, 1 H) ; HPLC-MS: m/z = 426 (M+1); Rt = 3.80 min.

Example 101 (General procedure 3) Morpholine-4-carboxylic acid 3-(2, 5-dimethoxy-phenyl)-4-methyl-2-oxo-2H-chromen-7-yl es- ter

The title compound (120 mg, 56% yield) was prepared from 3- (2, 5-dimethoxy-phenyl)-7- hydroxy-4-methyl-chromen-2-one (156 mg, 0.50 mmol) and 1-methyl-3- (morpholine-4- carbonyl)-3H-imidazol-1-ium iodide (165 mg, 0.51 mmol).

'H NMR (300MHz, CDCI3) : #2. 23 (s, 3H), 3.60 (br. s, 2H), 3.74 (br. s, 2H + s, 3H), 3.80 (m, 4H + s, 3H), 6.73 (m, 1H), 6.92 (m, 2H), 7.13 (m, 2H), 7.64 (d, 1H) ; HPLC-MSA): m/z= 426 (M+1); Rt = 3. 69 min.

Example 102 (General procedure 2) 2. 6-dimethyl-morpholine-4-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester The title compound was prepared from 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenol and 3- (2, 6-dimethyl-morpholine-4-carbonyl)-1-methyl-3H-imidazol-1-ium iodide. The crude product was purified by preparative HPLC (39%, colorless oil). HPLC-MS m/z = 397.1 (M+1), Rt: 4.64 min. i (200MHz ; CDCI3) : 1.22 (s, 3H), 1.25 (s, 3H), 2.50-3. 00 (m, 2H), 3.55-3. 9 (m, 2H), 4.00-3. 30 bd, 2H), 6.90-7. 50 (m, 5H), 7.91 (dd, 1 H), 8.44 (bs, 1 H).

Example 103 Dimethylcarbamic acid benzotriazol-1-yl ester Example 104 2-Oxo-N-p-tolylacetamide O-(cyclohexylcarbamoyl)-oxime Example 105 10, 11-Dihydro-dibenzo [a, d] cyclohepten-5-one O-cyclohexylcarbamoyl-oxime Example 106 1- (4-Chlorophenyl)-non-1-en-3-one O-cyclohexylcarbamoyl-oxime Example 107 1,7, 7-Trimethyl-bicyclo [2.2. 1] heptan-2-one O-cyclohexylcarbamoyl-oxime Example 108 1- (4-Bromophenyl)-6-methyl-hept-1-en-3-one O-isopropylcarbamoyl-oxime

Example 109 1- (4-Chloro-phenyl)-non-1-en-3-one O-isopropylcarbamoyl-oxime Example 110 4-Bromo-2- (4-chlorobenzyl)-2H-pyrazole-3-carbaldehyde O-methylcarbamoyl-oxime Example 111 1- (4-Bromophenyl)-6-methyl-hept-1-en-3-one 0-propylcarbamoyl-oxime Example 112 N- (4-Fluorobenzylcarbamoyloxy)-isobutyrimidoyl chloride<BR> <BR> Example 113<BR> N-(2-Hydroxy-2-phenylethylcarbamoyloxy)-isobutyrimidoyl chloride Example 114 Dimethylcarbamic acid 6-methanesulfonyl-indol-1-yl ester Example 115 1-Biphenyl-4-yl-3-methylamino-propenone-cyclohexyl-carbamic acid Example 116 Dimethylcarbamic acid 4-oxo-1,2, 3-benzotriazin-3-yl ester Example 117 [1- (3-Chloro-5-trifluoromethyl-pyridin-2-yl)-1 H-pyrrol-2-yl]-carbamic acid 4-chloro-phenyl ester Example 118 (General procedure 6) N-Methyl-N-phenyl-5-hexylsulfanyl-3-p-tolyl- [1, 2,4] triazole-1-carboxamide The title compound was prepared from p-toluoyl chloride, 1-bromo-hexane and N-methyl- pheny-Icarbamoyl chloride. The crude product was recrystallized (ethanol/water) ; HPLC-MS m/z = 409.2 (M+1), Rt: 6.66 min.

#H(300MHz ; [2H6] DMSO): 0.87 (t, 3H), 1. 20-1. 35 (m, 4H), 1.35-1. 48 (m, 2H), 1.72 (Qi, 2H), 2.99 (s, 3H), 3.25 (t, 2H), 3.46 (s, 3H), 7.13-7. 30 (m, 5H), 7.36 (t, 2H), 7.52 (d, 2H).

Example 119 (General procedure 6) N-Methyl-N-phenethyl-5-ethyl-3- (4-chlorophenyl)- [1, 2,4] triazole-1-carboxamide The title compound was prepared from 4-chlorobenzoyl chloride, 1-bromo-ethane and N- methyl-phenethyl-carbamoyl chloride. The crude product was subjected to preparative HPLC; HPLC-MS m/z = 401.1 (M+1), Rt: 6. 17 min. i (300MHz ; [2H6] DMSO): 1.37 (t, 3H), 2.98 (t, 2H), 3.11 (bs, 3H), 3.23 (Q, 2H), 3.80 (m, 2H), 7.10-7. 40 (m, 5H), 7.58 (d, 2H), 8.03 (d, 2H).

Example 120 (General procedure 6) [3- (4-Chlorophenyl)-5-methylsulfanyl- [1, 2,4] triazol-1-yl]-morpholin-4-yl-methanone The title compound was prepared from 4-chlorobenzoyl chloride, methyl iodide and mor- pholine-4-carbonyl chloride. The crude product was used without further purification; HPLC- MS m/z = 339.1 (M+1), Rt: 4.68 min. ci (300MHz ; [2H6] DMSO) : 2.68 (s, 3H), 3.25-3. 65 (m, 4H), 3.65-3. 85 (m, 4H), 7.58 (d, 2H), 8.03 (d, 2H).

Example 121 (General procedure 6) N, N-Dimethyl-5-methylsulfanyl-3-naphthalen-2-yl- [1, 2, 4] triazole-1-carboxamide The title compound was prepared from 2-naphthoyl chloride, methyl iodide and dimethyl car- bamoyl chloride. The crude product was recrystallized from ethanol ; HPLC-MS m/z = 313.2 (M+1), Rt: 4.91 min. i (300MHz ; [2H6] DMSO): 2.74 (s, 3H), 3. 18 (s, 6H), 7.53-7. 65 (m, 2H), 7. 92-8. 00 (m, 1H), 8.00-8. 17 (m, 3H), 8.62 (s, 1H).

Example 122 (General procedure 6) N, N-Dimethyl-3- (4-chloro-phenyl)-5-ethylsulfanyl- [1, 2,4] triazole-1-carboxamide The title compound was prepared from 2-naphthoyl chloride, methyl iodide and dimethyl car- bamoyl chloride. The crude product was recrystallized from ethanol ; HPLC-MS m/z = 311.0 (M+1), Rt: 5.13 min. cli (300MHz ; [2H6] DMSO): 1.39 (t, 3H), 3.13 (bs, 6H), 3.26 (q, 2H), 7.58 (d, 2H), 8. 03 (d, 2H).

Example 123 (General procedure 6) N, N-Dimethyl-3-biphenyl-4-yl-5-methylsulfanyl- [1, 2,4] triazole-1-carboxamide The title compound was prepared from 3-biphenylcarbonyl chloride, methyl iodide and di- methyl carbamoyl chloride. The crude product was without further purification; HPLC-MS m/z = 339. 1 (M+1), Rt: 5. 27 in.

#H(300MHz ; [2H6]DMSO : 2.70 (s, 3H), 3.16 (bs, 6H), 7.40 (t, 1H), 7.50 (t, 2H), 7.73 (d, 2H), 7.82 (d, 2H), 8.12 (d, 2H).

Example 124 N, N-Dimethyl-3- (4-chloro-phenyl)-5-methylsulfanyl- [1, 2,4] triazole-1-carboxamide Example 126 N- (4-Chlorophenyl)-3- (4-chlorophenyl)-5- (3-hydroxypropyl)-pyrazole-1-carboxamide.

Example 127 5-Morpholin-4-yl-3- (4-phenoxyphenyl)-pyrazole-1-carboxylic acid phenethylamide Example 128 N-Phenyl-4- (4-chlorobenzenesulfonyl)-5- (4-chlorophenyl)-pyrazole-1-carboxamide Example 129 N- (3, 4-Dichlorophenyl)-2-phenyl-benzimidazole-1-carboxamide Example 130 Dimethy-carbamic acid 5-isopropylsulfanyl-4-(3-trifluoromethyl-phenyl)-4H-[1, 2, 4] triazol-3-yl ester Example 131 Dimethyl carbamic acid 1-benzyl-2-oxo-3, 5-diphenyl-1, 2-dihydro-pyridin-4-yl ester Example 132 Dimethyl-carbamic acid 7-methoxy-1-methyl-2-oxo-1, 2-dihydro-quinolin-4-yl. ester Example 133 Dimethyl carbamic acid 4- (3-chloro-phenyl)-5- (4-methyl-benzylsulfanyl)-4H- [1, 2,4] triazol-3-yl

ester Example 134 (General procedure 7) 4-Methyl-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester The hydrochloride of the title compound was prepared from 4- (5-trifluoromethyl-pyridin-2- yloxy)-phenol and 1-methylpiperazine. White solid, m. p. 249-250 °C (decomp. ); HPLC-MS m/z = 458 (M+H), Rt: 3.15 min. ; 1H NMR (DMSO-d6) : J 11.56 (br, 1 H, NH), 8.61-8. 54 (br, 1 H, py-H6), 8.30-8. 20 (m, 1 H, py-H4), 7.32-7. 19 (d+ br s, 5H, py-H3 + C6H4), 4.5-3. 0 (br, 10H, 8 CH + H2O), 2.79 (s, 3H, CH3) ; IR (KBr): v 1713 (C=O).

Example 135 (General procedure 7) 4-Benzyl-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester The hydrochloride of the title compound was prepared from 4- (5-trifluoromethyl-pyridin-2- yloxy)-phenol and 1-benzylpiperazine. White solid, m. p. 229-231 °C ; HPLC-MS m/z = 458 (M+H), Rt : 3.15 min. ;'H NMR (DMSO-d6) : 11.17 (br, 1 H, NH), 8. 61-8. 54 (br, 1 H, py-H6), 8.30-8. 20 (m, 1H, py-H4), 7.74-7. 59 (m, 2H, arom. ), 7.52-7. 41 (m, 3H, arom. ), 7.31-7. 17 (d+ br s, 5H, py-H3 + C6H4), 4.5-4. 0 (br, 4H, CH2 + 2 CH), 3.8-3. 0 (br, 8H, 6 CH + H2O) ; IR (KBr): v 1720 (C=O).

Example 136 (General procedure 7) 4-(2-Hydroxyethyl)-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester The hydrochloride of the title compound was prepared from 4- (5-trifluoromethyl-pyridin-2- yloxy)-phenol and 1- (2-hydroxyethyl)-piperazine. White solid, m. p. 255 °C ; HPLC-MS m/z = 412 (M+H), Rt: 2.12 min. ;'H NMR (DMSO-d6) : a 10.66 (br, 1H, NH), 8.61-8. 54 (br, 1H, py- H6), 8.30-8. 20 (m, 1 H, py-H4), 7.32-7. 20 (d+ br s, 5H, py-H3 + C6H4), 5.39 (br, 1 H, OH), 4.18 (br, 2H), 3.87-3. 70 (br t, 2H), 3.70-3. 02 (br, 8H + water) ; IR (KBr): v 1714 (C=O).

Example 137 (General procedure 7) 4-(2-Oxo-2-pyrrolidin-1-yl-ethyl)-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2- yloxy)-phenyl ester

The hydrochloride of the title compound was prepared from 4- (5-trifluoromethyl-pyridin-2- yloxy)-phenol and 1- (pyrrolidinocarbonylmethyl)-piperazine. White solid, m. p. 224 °C ; HPLC- MS m/z = 479 (M+H), Rt: 2.73 min. ; 1H NMR (DMSO-d6) : 610. 43 (br, 1H, NH), 8.62-8. 52 (br, 1 H, py-H6), 8.31-8. 20 (m, 1 H, py-H4), 7.34-7. 18 (d+ br s, 5H, py-H3 + C6H4), 4.40- 3.05 (br, CH2 at 4.26 + water at 3.37 + N-C-H), 2.03-1. 72 (m, 4H, CH2).

Example 138 (General procedure 7) 4-Phenyl-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester The hydrochloride of the title compound was prepared from 4- (5-trifluoromethyl-pyridin-2- yloxy)-phenol and 1-phenyl-piperazine (0.5 mmol). The crude product (0.15 g) was parti- tioned between ethyl acetate (4 ml) and ethyidiisopropylamine (0.04 ml) dissolved in water (4 ml). The organic layer was washed with water (2 x 5 ml), dried over sodium sulfate. The dry- ing agent was filtered off, and the solvent was removed from the filtrate in vacuo to give the title compound (0.095 g). White crystals, m. p. 117 °C ; HPLC-MS m/z = 444 (M+H), Rt: 5.12 min. ;'H NMR (DMSO-d6) : 8 8.61-8. 55 (br, 1H, py-H6), 8.29-8. 20 (m, 1H, py-H4), 7.32- 7.14 (m, 7H, py-H3 + C6H4 + 2 arom. ), 7.05-6. 71 (m, 3H, arom. ), 3. 83-3. 51 (br, 4H, 2 CH2), 3.28-2. 99 (m, 4H, 2 CH2).

Example 139 (General procedure 8) Methyl-phenyl-carbamic acid pyrazol-1-yl ester The title compound was prepared from 1-hydroxypyrazole and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to flash chromatography (Quad flash 25, EtOAc- heptane) (79%, oil which slowly crystallizes). HPLC-MS m/z = 218. 1 (M+1), Rt: 2.82 min. Mp 63-67 °C j (300MHz ; CDCI3) : 3.45 (bs, 3H), 6.28 (s, 3H), 7.30-7. 47 (m, 7H).

Example 140 (General procedure 8) Methyl-phenyl-carbamic acid 4-bromo-pyrazol-1-yl ester The title compound was prepared from 1-hydroxy-4-bromopyrazole and N-methyl-N- phenylcarbamoyl chloride. The crude product was subjected to flash chromatography (Quad flash 25, EtOAc-heptane) (89%, oil). HPLC-MS m/z = 298.0 (M+1), Rt: 3.77 min. i (300MHz ; CDCI3) : 3.44 (bs, 3H), 7.32-7. 47 (m, 7H).

Example 141 (General procedure 8) Methyl-phenyl-carbamic acid 3,4, 5-tribromo-pyrazol-1-yl ester The title compound was prepared from 1-hydroxy-3, 4, 5-bromopyrazole and N-methyl-N- phenylcarbamoyl chloride. The crude product was subjected to flash chromatography (Quad flash 25, EtOAc-heptane) (93%, colorless crystals). HPLC-MS m/z = 455. 8 (M+1), Rt: 4.88 min. Mp 115-119°C $ (300MHz ; CDCI3) : 3.44 (bs, 3H), 7.36-7. 48 (m, 5H).

Example 142 (General procedure 8) Methyl-phenyl-carbamic acid 3- (4-methoxy-phenyl)-pyrazol-1-yl ester The title compound was prepared from 1-hydroxy-3- (4-methoxyphenyl) pyrazole and N- methyl-N-phenylcarbamoyl chloride. The crude product was subjected to flash chromatogra- phy (Quad flash 25, EtOAc-heptane) (93%, oil). HPLC-MS m/z = 346.1 (M+Na), Rt: 4.21 min. ci (300MHz ; CDCI3) : 3.45 (bs, 3H), 3.84 (s, 3H), 6.50 (d, 1 H), 6.91 (d, 2H), 7. 30-7. 48 (m, 6H), 7.70 (d, 2H).

Example 143 (General procedure 8) Methyl-phenyl-carbamic acid imidazol-1-yl ester The title compound was prepared from 1-hydroxyimidazole and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to flash chromatography (Quad flash 25, EtOAc- heptane) (68%, oil). HPLC-MS m/z = 218.1 (M+1), Rt: 1.53 min. cl, (300MHz ; CDCI3) : 3.45 (bs, 3H), 7.00 (bs, 1 H), 7.05 (bs, 1 H), 7.32-7. 49 (m, 5H), 7.55 (bs, 1H).

Example 144 (General procedure 8) Methyl-phenyl-carbamic acid [1,2, 3] triazol-1-yl ester The title compound was prepared from 1-hydroxy-1,2, 3-triazole and N-methyl-N- phenylcarbamoyl chloride. The crude product was subjected to flash chromatography (Quad flash 25, EtOAc-heptane) (80%, oil). HPLC-MS m/z = 219. 1 (M+1), Rt: 2.50 min. Mp 105-106 °C. i (300MHz ; CDCI3) : 3.46 (bs, 3H), 7.00 (bs, 1 H), 7.05 (bs, 1 H), 7.31-7. 48 (m, 5H), 7.62 (bs, 1 H), 7.74 (s, 1 H).

Example 145 (General procedure 7) 4- (Isopropylcarbamoyl-methyl)-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-

yloxy)-phenyl ester The hydrochloride of the title compound was prepared from 4- (5-trifluoromethyl-pyridin-2- yloxy)-phenol and 1-methyl-piperazine. White solid, m. p. 234-235 °C ; HPLC-MS m/z = 466 (M+H), Rt: 2.75 min. ;'H NMR (DMSO-d6) : a 10.50 (br, 1H, NH), 8.66-8. 54 (br, 2H, NH + py-H6), 8.30-8. 20 (dd, 1 H, py-H4), 7.31-7. 20 (d+ br s, 5H, py-H3 + C6H4), 4.00-3. 82 (br m, 5H, methin + 4 CH), 3.70-3. 09 (br, 9H, 6H + water), 1.11 (d, 6H, CH3).

Example 146 (General procedure 9) 4-Cyclopentyl-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester.

The hydrochloride of the title compound was prepared from 4- (5-trifluoromethyl-pyridin-2- yloxy)-phenyl chloroformate and 1-cyclopentyl-piperazine. White solid, m. p. 294-295 °C ; HPLC-MS m/z = 436 (M+H), Rt : 2.92 min. ;'H NMR (DMSO-d6) : a 11.15 (br, 1H, NH), 8.60- 8. 55 (br, 1 H, py-H6), 8.29-8. 20 (m, 1 H, py-H4), 7.32-7. 21 (d+ br s, 5H, py-H3 + C6H4), 4.35 - 3. 98 (br, 2H), 3.72-3. 37 (br m, 5H), 3.29-2. 97 (br, 2H), 2.12-1. 45 (br m, 8H).

Example 147 (General procedure 9) 4-Butyl-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester The hydrochloride of the title compound was prepared from 4- (5-trifluoromethyl-pyridin-2- yloxy)-phenyl chloroformate and 1-butyl-piperazine. White solid, m. p. 221-222 °C ; HPLC- MS m/z = 424 (M+H), Rt: 2.94 min. ;'H NMR (DMSO-d6) : a 10.86 (br, 1H, NH), 8.60-8. 55 (br, 1 H, py-H6), 8.29-8. 21 (m, 1 H, py-H4), 7.31-7. 22 (d+ br s, 5H, py-H3 + C6H4), 4.32- 4.03 (br, 2H), 3.65-3. 44 (br m, 4H), 3.28-2. 97 (br, 4H), 1.81-1. 60 (br m, 2H), 1.45-1. 22 (br, 4H), 0.92 (t, 3H, CH3).

Example 148 (General procedure 1) 4- (Methyl-phenyl-carbamoyloxy)-benzoic acid 2, 5-dioxo-pyrrolidin-1-yl ester The title product was prepared from 4-Hydroxy-benzoic acid 2, 5-dioxo-pyrrolidin-1-yl ester and N-methyl-N-phenylcarbamoyl chloride. The crude product was recrystallized from

methanol (74%, white crystals).

'H NMR (CDC13) : 8.13 (d, 2H), 7. 38-7. 55 (m, 6H), 7.30 (t, 1H), 3.37 (s, 3H), 2.89 (s, 4H).

Example 149 (General procedure 10) 4-Hydroxymethyl-piperidine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl es- ter The title product was prepared from 4- (5-trifluoromethyl-pyridin)-2-yloxy)-phenol and 4- hydroxymethylpiperidine. The crude product was subjected to flash chromatography (ethyl acetate/heptane, 1: 2 o 2 : 1) (78%, light yellow oil). The purified product was crystallized from ethyl acetate/heptane (51%, white solid). HPLC-MS: m/z= 397.1 (M+1); Rt: 4.08 min.

'H NMR (CDCI3) : 8.44 (s, 1H), 7.88 (dd, 1H), 7.17 (d, 2H), 7.13 (d, 2H), 7.00 (d, 2H), 4.45- 4.20 (bs, 2H), 3.55 (t, 2H), 3.10-2. 75 (m, 2H), 1.95-1. 65 (m, 3H), 1.47 (t, 1H), 1.29 (dq, 2H).

Example 150 (General procedure 10) 4-Oxo-piperidine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester The title product was prepared from 4- (5-trifluoromethyl-pyridin)-2-yloxy)-phenol and 4- piperidone monohydrate. The solvent used was a mixture of dichloromethane and dimethyl- formamide (1: 1). The crude product was subjected to preparative HPLC (7%, oil). HPLC-MS: m/z= 381.1 (M+1); Rt: 4.17 min.

Example 151 (General procedure 10) 4- [5- (4-Dimethylamino-phenyl)-l H-pyrazol-3-yl]-piperidine-1-carboxylic acid 4- (5- trifluoromethyl-pyridin-2-yloxy)-phenyl ester The title product was prepared from 4- (5-trifluoromethyl-pyridin)-2-yloxy)-phenol and N, N- dimethyl-4- [3- (4-piperidinyl)-1 H-pyrazol-5-yl] aniline. The solvent used was a mixture of di- chloromethane and dimethylformamide (1: 2). The crude product was subjected to prepara- tive HPLC (4%, oil). HPLC-MS: m/z= 552.2 (M+1); Rt: 4.17 min.

'H NMR (CDCI3) : 8.44 (d, 1H), 7. 89 (dd, 1H), 7.53 (d, 2H), 7.22-7. 10 (m, 4H), 7.00 (d, 1H), 6.73 (d, 2H), 6.27 (s, 1H), 4.45-4. 20 (ds, 2H), 3.25-2. 95 (m, 3H), 2.88 (s, 6H), 2.15-2. 00 (m, 2H), 1. 90-1. 70 (dq, 2H).

Example 152 (General procedure 10)

4- (5-Furan-2-yl-1 H-pyrazol-3-yl)-piperidine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2- yloxy)-phenyl ester The title product was prepared from 4- (5-trifluoromethyl-pyridin)-2-yloxy)-phenol and 4- [3- (2- fury))-1 H-pyrazol-5-yl] piperidine. The solvent used was a mixture of dichloromethane and di- methylformamide (1: 2). The crude product was subjected to preparative HPLC (4%, oil).

HPLC-MS: m/z= 499.1 (M+1); Rt: 4.60 min.

'H NMR (CDCI3) : 8.44 (d, 1H), 7.89 (dd, 1H), 7.45 ( (dd, 1H), 7.24-7. 10 (m, 4H), 6.99 (d, 1H), 6.62 (d, 1 H), 6.48 (dd, 1 H), 6.34 (s, 1 H), 4.40-4. 25 (bs, 2H), 3.25-2. 85 (m, 3H), 2.08 (d, 2H), 1.79 (dq, 2H).

Example 153 (General procedure 10) 4-Benzylamino-piperidine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester The title product was prepared from 4- (5-trifluoromethyl-pyridin)-2-yloxy)-phenol and benzyl- piperidin-4-yl-amine. The crude product was subjected to preparative HPLC (20%, oil).

HPLC-MS: m/z = 472.2 (M+1); Rt: 3.34 min.

Example 154 (General procedure 10) 4- (3, 4-Dihydro-1 H-isoquinolin-2-ylmethyl)-piperidine-1-carboxylic acid 4- (5-trifluoromethyl- pyridin-2-yloxy)-phenyl ester The title product was prepared from 4- (5-trifluoromethyl-pyridin)-2-yloxy)-phenol and 2- Piperidin-4-ylmethyl-1, 2,3, 4-tetrahydro-isoquinoline. The crude product was subjected to preparative HPLC (12%, oil). HPLC-MS: m/z= 512.2 (M+1); Rt: 3.21 min.

Example 155 (General procedure 1) Methyl-phenyl-carbamic acid 4- (1, 3, 5-trimethyl-1 H-pyrazol-4-ylmethyl)-phenyl ester The title product was prepared from 4- [ (1, 3, 5-trimethyl-1 H-pyrazol-4-yl) methyl] phenol and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC (88%, oil). HPLC-MS: m/z= 350.0 (M+1); Rt: 3.52 min. (66% purity).

Example 156 (General procedure 10) 3-Hydroxymethyl-piperidine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl es-

ter The title product was prepared from 4- (5-trifluoromethyl-pyridin)-2-yloxy)-phenol and 3- hydroxymethyl-piperidine. The crude product was subjected to flash chromatography (Quad Flash 12, ethyl acetate/heptane 1: 2). (56%, colourless oil). HPLC-MS: m/z= 397.1 (M+1); Rt: 4.19 min.

'H NMR (DMSO-d6, 90 °C) : 8.37 (s, 1H), 8.00 (dd, 1H), 6.95-7. 10 (m, 5H), 4.09 (bs, 1H), 3.91 (dd, 1H), 3.78 (d, 1H), 3.21 (m, 1H), 3.15 (t, 1H), 2.80-2. 90 (m, 1H), 2.65 (t, 1H), 1.45- 1.70 (m, 3H), 1.25-1. 45 (m, 1 H), 1.08 (q, 1 H).

Example 157 (General procedure 10) 3-Hydroxy-piperidine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester The title product was prepared from 4- (5-trifluoromethyl-pyridin)-2-yloxy)-phenol and 3- hydroxy-piperidine. The crude product was subjected to flash chromatography (Quad Flash 12, ethyl acetate/heptane (1: 2) (56%, colourless oil). HPLC-MS: m/z = 383.0 (M+1); Rt: 3.98 min.

'H NMR (CDCI3) : 8.43 (s, 1H), 7.89 (dd, 1H), 7.23-7. 10 (m, 4H), 7.00 (d, 1H), 3.80-4. 00 (m, 2H), 3.60-3. 80 (m, 1 H), 3.25-3. 50 (m, 2H), 1.80-2. 05 (m, 2H), 1.50-1. 70 (m, 3H).

Example 158 (General procedure 10) 4-Benzyl-4-hydroxy-piperidine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester The title product was prepared from 4- (5-trifluoromethyl-pyridin)-2-yloxy)-phenol and 4- benzyl-4-hydroxypiperidine. The crude product was subjected to flash chromatography (Quad Flash 12, ethyl acetate/heptane (1: 2) (48%, colourless oil). HPLC-MS: m/z= 473.0 (M+1); Rt: 5.04 min.

'H NMR (CDCI3) : 8.44 (s, 1H), 7.89 (dd, 1H), 7.28-7. 45 (m, 3H), 7.10-7. 24 (m, 6H), 7.00 (d, 1H), 4.00-4. 14 (bs, 2H), 3.15-3. 45 (dt, 2H), 2. 81 (s, 2H), 1.66-1. 85 (dt, 2H), 1.55-1. 65 (m, 2H), 1.27 (s, 1 H).

Example 159 (General procedure 1) Methyl-phenyl-carbamic acid 4- (2-cyano-ethyl)-phenyl ester

The title product was prepared from 3- (4-hydroxyphenyl) proprionitrile and N-methyl-N- phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC (11 %, col- ourless oil). HPLC-MS: m/z = 281.2 (M+1); Rt: 3.75 min, purity 80%.

'H NMR (CDCI3) : 7.26-7. 50 (m, 7H), 7.00-7. 15 (m, 2H), 3.42 (s, 3H), 2.94 (t, 2H), 2.59 8t, 2H).

Example 160 (General procedure 1) Methyl-phenyl-carbamic acid 4- ( [1, 2,3, 4] thiatriazol-5-ylamino)-phenyl ester The title product was prepared from 4- (1, 2,3, 4-thiatriazol-5-ylamino) phenol and N-methyl-N- phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC. (10%, light brown solid material). HPLC-MS: m/z = 328.0 (M+1); Rt: 3.69 min, purity 81 %.

'H NMR (CDCI3) : 7.61 (d, 2H), 7.38-7. 52 (m, 4H), 7.19-7. 35 (m, 2H), 6.86-6. 95 (m, 1H), 3.35 (s, 3H), 3.33 (s, 1 H).

Example 161 (General procedure 1) Methyl-phenyl-carbamic acid 4-pentyl-phenyl ester The title product was prepared from 4-pentylphenol and N-methyl-N-phenylcarbamoyl chlo- ride. The crude product was subjected to preparative HPLC. (4%, light brown oil). HPLC-MS: m/z= 298. 2 (M+1); Rt: 5.61 min.

'H NMR (CDCI3) : 7.31-7. 50 (m, 4H), 7.18-7. 30 (m, 1H), 7.13 (d, 2H), 7.00 d, 2H), 3.42 (s, 3H), 2.57 (t, 2H), 1.58 (qi, 2H), 1.20-1. 40 (m, 4H), 0.87 (t, 3H).

Example 162 (General procedure 1) Methyl-phenyl-carbamic acid 4- (2-methoxy-ethyl)-phenyl ester The title product was prepared from 4- (2-methoxyethyl) phenol and N-methyl-N- phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC. (4%, light yellow oil). HPLC-MS: m/z = 286.1 (M+1); Rt: 4.01 min.

1H NMR (CDC13) : 7.30-7. 48 (m, 4H), 7.12-7. 30 (m, 3H), 7.03 (d, 2H), 3.56 (t, 2H), 3.42 (s, 3H), 3.33 (s, 3H), 2. 85 (t, 2H).

Example 163 (General procedure 10) 4-Hydroxy-piperidine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester

The title product was prepared from 4- (5-trifluoromethyl-pyridin)-2-yloxy)-phenol and 4- hydroxypiperidine. The crude product was subjected to flash chromatography (ethyl ace- tate/heptane (1: 1) (48%, light yellow oil). HPLC-MS: m/z = 383.0 (M+1); Rt: 3.88 min. purity 93%.

'H NMR (CDCI3) : 8.44 (s, 1H), 7.89 (dd, 1H), 7.08-7. 20 (m, 4H), 6.99 (d, 1H), 3.85-4. 10 (m, 3H), 3.20-3. 45 (m, 2H), 1.85-2. 02 (m, 2H), 1.50-1. 70 (m, 3H).

Example 164 (General procedure 1) Methyl-phenyl-carbamic acid 4-acetyl-phenyl ester The title product was prepared from 4'-hydroxyacetophenone and N-methyl-N- phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC. (78%, colourless oil). HPLC-MS: m/z= 270.1 (M+1); Rt: 3.62 min.

'H NMR (CDCI3) : 7.96 (d, 2H), 7.15-7. 7.48 (m, 7 H), 3.43 (s, 3H), 2.58 (s, 3H).

Example 165 (General procedure 1) Methyl-phenyl-carbamic acid pyridin-4-yl ester The title product was prepared from 4-hydroxypyridine and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC. (11 %, yellow solid). HPLC- MS: m/z = 229.2 (M+1); Rt: 1.66 min, purity: 67%.

Example 166 (General procedure 1) Methyl-phenyl-carbamic acid pyridin-3-yl ester The title product was prepared from 3-hydroxypyridine and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC. (94%, colourless oil).

HPLC-MS: m/z = 229.2 (M+1); Rt : 2.54 min.

'H NMR (CDCI3) : 10.70 (bs, 1H), 8.50 (d, 1H), 8.45-8. 65 (m, 1H), 7.70-7. 90 (m, 1H), 7.51 (dd, 1 H), 7.42 (d, 2H), 7.34 (d, 2H), 7.28-7. 37 (m, 1 H), 3.43 (s, 3H).

Example 167 (General procedure 1) Methyl-phenyl-carbamic acid 6-methyl-pyridin-3-yl ester The title product was prepared from 3-hydroxy-6-methyl-pyridine and N-methyl-N-

phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC. (79%, colourless oil). HPLC-MS: m/z= 243.1 (M+1); Rt: 2.24 min.

1 NMR (CDCI3) : 10.8 (bs, 1H), 8.54 (m, 1H), 7.76 (m, 1H), 7.26-7. 50 (m, 6H), 3.42 (s, 3H), 2.69 (s, 3H).

Example 168 (General procedure 1) Methyl-phenyl-carbamic acid isoquinolin-1-yl ester The title product was prepared from and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC. (15%, colourless oil). HPLC-MS : m/z= 279.1 (M+1); Rt: 3.67 min.

Example 169 (General procedure 1) Methyl-phenyl-carbamic acid 3-phenoxy-phenyl ester The title product was prepared from 3-phenoxyphenol and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC. (79%, colourless oil).

HPLC-MS: m/z= 320.1 (M+1); Rt: 5.16 min.

1H NMR (CDCI3) : 7.20-7. 50 (m, 8 H), 7.11 (t, 1 H), 6.95-7. 06 (m, 2H), 6.70-6. 93 (m, 3H), 3.40 (s, 3H).

Example 170 (General procedure 1) Methyl-phenyl-carbamic acid 3-acetyl-phenyl ester The title product was prepared from m-hydroxyacetophenone and N-methyl-N- phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC (62%, col- orless oil). HPLC-MS: m/z = 270.1 (M+1); Rt: 3.56 min.

'H NMR (CDCI3) : 7.78 (d, 1H), 7. 68 (s, 1H), 7.22-7. 50 (m, 7H), 3.43 (s, 3H), 2.58 (s, 3H).

Example 171 (General procedure 1) Methyl-phenyl-carbamic acid 4-acetyl-2-carbamoyl-phenyl ester The title product was prepared from 5-acetylsalicylamide and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC. (87%, white solid). HPLC- MS : m/z= 313.1 (M+1); Rt: 2.51 min.

'H NMR (CDC13) : 8.47 (bs, 1H), 8.08 (dd, 1H), 7.30-7. 52 (m, 6H), 6.05 (bs, 1H), 5.38 (bs, 1H), 3.43 (s, 3H), 2.61 (s, 3H).

Example 172 (General procedure 1) Methyl-phenyl-carbamic acid 4-acetyl-3-methyl-phenyl ester The title product was prepared from 4'-hydroxy-2'-methylacetophenone and N-methyl-N- phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC. (76%, white crystals). HPLC-MS: m/z = 284.2 (M+1) ; Rt: 3.95 min.

'H NMR (CDC13) : 7.72 (d, 1H), 7.22-7. 47 (m, 5H), 6.90-7. 12 (m, 2H), 3.43 (s, 3H), 2.55 (s, 3H), 2.52 (s, 3H).

Example 173 (General procedure 1) Methyl-phenyl-carbamic acid 1-oxo-indan-4-yi ester The title product was prepared from 4-hydroxyindanone and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC. (77%, light yellow oil).

HPLC-MS : m/z= 282.1 (M+1); Rt: 3.54 min.

'H NMR (CDCI3) : 7.61 (d, 1H), 7.27-7. 50 (m, 7H), 3.45 (s, 3H), 3.00 (ds, 2H), 2.67 (t, 2H).

Example 174 (General procedure 1) Methyl-phenyl-carbamic acid benzothiazol-2-yl ester The title product was prepared from 2-benzothiazolol and N-methyl-N-phenylcarbamoyl chlo- ride. The crude product was subjected to preparative HPLC. (70%, white crystals). HPLC- MS: m/z = 307.1 (M+1); Rt: 4.24 min, purity 85%.

'H NMR (CDCI3) : 7.78 (m, 2H), 7. 28-7. 50 (m, 7H), 3.40-3. 70 (d, 3H).

Example 175 (General procedure 1) Methyl-phenyl-carbamic acid 5-oxo-5,6, 7, 8-tetrahydro-naphthalen-2-yl ester The title product was prepared from 6-hydroxy-1-tetralone and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC. (49%, colorless oil). HPLC- MS : m/z = 296.2 (M+1); Rt: 3.90 min.

'H NMR (CDC1s) : 8.04 (d, 2H), 7.27-7. 50 (m, 5H), 7.00-7. 10 (m, 2H), 3.42 (s, 3H), 2.94 (t,

2H), 2.63 (t, 2H), 2.12 (qu, 2H).

Example 176 (General procedure 1) Methyl-phenyl-carbamic acid benzo [d] isoxazol-3-yl ester The title product was prepared from benzo [d] isoxazol-3-ol and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC. (53%, colorless oil). HPLC- MS: m/z = 291.1 (M+23); Rt: 4.05 min.

'H NMR (CDCI3) : 7.60-7. 75 (m, 1H), 7.49-7. 60 (m, 2H), 7.38-7. 48 (m, 4H), 7.28-7. 36 (m, 2H), 3.46 (s, 3H).

Example 177 (General procedure 1) Methyl-phenyl-carbamic acid pyridin-2-yl ester The title product was prepared from 2-hydroxypyridine and N-methyi-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC. (57%, colorless oil). HPLC- MS: m/z= 229.1 (M+23); Rt: 2.80 min.

'H NMR (CDCI3) : 8.38 (d, 1H), 7.75 (t, 1H), 7.35-7. 45 (m, 4H), 7.22-7. 34 (m, 1H), 7.14-7. 21 (t, 1H), 6.99-7. 15 (bs, 1H), 3.44 (s, 3H).

Example 178 (General procedure 1) Methyl-phenyl-carbamic acid 1- (methyl-phenyl-carbamoyl)-1 H-benzimidazol-2-yl ester The title product was prepared from 2-hydroxybenzimidazole and N-methyl-N- phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC. (14%, white crystals). HPLC-MS: m/z = 401.2 (M+1); Rt : 3.88 min, purity: 83%.

'H NMR (CDCI3) : 7.32 (dd, 2H), 7.24-7. 28 (m, 2H), 7.21-7. 24 (m, 2H), 7. 29 (t, 1H), 7.12-7. 19 (m, 5H), 7. 09-7. 15 m, 2H), 3. 28 (s, 6H).

Example 179 (General procedure 1) Methyl-phenyl-carbamic acid 4-[(pyridine-3-carbonyl)-amino]-phenyl ester The title product was prepared from N- (4-Hydroxy-phenyl)-nicotinamide and N-methyl-N- phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC. (1 %, light yellow crystals). HPLC-MS: m/z= 348.1 (M+1); Rt: 2.96 min.

Example 180 (General procedure 11) 4-Pyrrolidin-1-yl-piperidine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester The title product was prepared from 4- (5-trifluoromethyl-pyridin)-2-yloxy)-phenol and 4- (1- pyrrolidinyl) piperidine. The crude product was used without further purification (68%, white solid). HPLC-MS: m/z = 436.2 (M+1); Rt : 2.98 min.

'H NMR (DMSO-d6): 10.90 (bs, 1H), 8.57 (s, 1H), 8.24 (dd, 1H), 7.15-7. 30 (m, 5H), 4.00- 4.40 (m, 2H), 3.45-3. 60 (m, 2H), 2.75-3. 25 (m, 4H), 2.05-2. 25 (d, 2H), 1.80-2. 05 (m, 5H), 1.60-1. 80 (m, 2H).

Example 181 (General procedure 12) Methyl-o-tolyl-carbamic acid 4- (trifluoromethyl-pyridin-2-yloxy)-phenyl ester The title product was prepared from 4- (5-trifluoromethyl-pyridin)-2-yloxy)-phenol and N- methyl-o-toluidine. The crude product was subjected to preparative HPLC (51%, colorless oil). HPLC-MS: m/z= 403.2 (M+1); Rt : 4.89 min.

1H NMR (CDCI3) : 8. 40 (s, 1H), 7.87 (dd, 1H), 7.05-7. 18 (m, 4H), 6.96 (d, 1H), 3.30 (s, 3H), 2.36 (s, 3H).

Example 182 (General procedure 12) Methyl-pyridin-2-yl-carbamic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester The title product was prepared from 4- (5-trifluoromethyl-pyridin)-2-yloxy)-phenol and 2- (methylamino) pyridine. The crude product was subjected to preparative HPLC (55%, white solid). HPLC-MS: m/z = 390.1 (M+1); Rt : 4.31 min.

Example 183 (General procedure 12) Methyl-m-tolyl-carbamic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester The title product was prepared from 4- (5-trifluoromethyl-pyridin)-2-yloxy)-phenol and N- methyl-m-toluidine. The crude product was subjected to preparative HPLC (51 %, colorless oil). HPLC-MS : m/z = 403.2 (M+1); Rt : 4. 98 min.

'H NMR (CDCI3) : 8. 42 (s, 1H), 7. 88 (dd, 1H), 7.28 (d, 1H), 7.05-7. 25 (m, 7H), 6.97 (d, 1H), 3.41 (s, 3H), 2.38 (s, 3H).

Example 184 (General procedure 12) (3-Chloro-phenyl)-methyl-carbamic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyi ester The title product was prepared from 4- (5-trifluoromethyl-pyridin)-2-yloxy)-phenol and 3- chloro-N-methylaniline. The crude product was subjected to preparative HPLC (54%, color- less oil). HPLC-MS: m/z= 423.1 (M+1); Rt: 5.07 min.

1H NMR (CDC13) : 8.42 (m, 1 H), 7.88 (dd, 1 H), 7.39 (m, 1 H), 7.33 (t, 1 H), 7.22-7. 30 (m, 2H), 7.10-7. 7.22 (m, 4H), 6.99 (d, 1H), 3.43 (s, 3H).

Example 185 (General procedure 12) Methyl-p-tolyl-carbamic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester The title product was prepared from 4- (5-trifluoromethyl-pyridin)-2-yloxy)-phenol and N- methyl-p-toluidine. The crude product was subjected to preparative HPLC (54%, white solid).

HPLC-MS: m/z = 403.2 (M+1); Rt: 4.99 min.

1H NMR (CDCI3) : 8.42 (s, 1H), 7.87 (dd, 1H), 7.05-7. 30 (m, 8H), 6.98 (d, 1H), 3.40 (s, 3H), 2.36 (s, 3H).

Example 186 (General procedure 14) Methyl-phenyl-carbamic acid 4- (3-pyridin-3-yl-acryloyl)-phenyl ester The title product was prepared from 1- (4-hydroxy-phenyl)-3-pyridin-3-yl-prop-2-en-1-one and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC (56%, off-white solid). HPLC-MS: m/z = 359.0 (M+1); Rt: 3.27 min.

1 NMR (CDCI3) : 8.87 (d, 1H), 8.65 (dd, 1H), 8.03 (d, 2H), 7.97 (dt, 1H), 7.79 (d, 1H), 7.57 (d, 1 H), 7.33-7. 47 (m, 5H), 7.27-7. 33 (m, 3H), 3.44 (s, 3H), 3.49 (t, 1 H), 1.21 (t, 1 H).

Example 187 (General procedure 14) Methyl-phenyl-carbamic acid 4- [3- (3, 4, 5-trimethoxy-phenyl)-acryloyl]-phenyl ester The title product was prepared from 1- (4-hydroxyphenyl)-3- (3, 4, 5-trimethoxyphenyl) prop-2- en-1-one and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC (82%, yellow solid). HPLC-MS: m/z = 448.2 (M+1); Rt : 4.61 min.

'H NMR (CDC13) : 8.01 (d, 2H), 7.70 (d, 1H), 7.33-7. 47 (m, 4H), 7.28-7. 33 (m, 2H), 6.86 (s,

1H), 3.92 (s, 6H), 3.90 (s, 3H), 3.45 (s, 3H).

Example 188 (General procedure 14) Methyl-phenyl-carbamic acid 4-diethylcarbamoyl-2-methoxy-phenyl ester The title product was prepared from N, N-diethyl-4-hydroxy-3-methoxy-benzamide and N- methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC (58%, colorless oil). HPLC-MS: m/z= 357.1 (M+1); Rt: 3.64 min.

1 NMR (CDCI3) : 7.34-7. 44 (m, 4H), 7.21-7. 28 (m, 1 H), 7.03-7. 09 (d, 1 H), 6.99 (d, 1 H), 6.90 (dd, 1H), 3.87 (s, 3H), 3.15-3. 65 (bs, 4H), 3.43 (s, 3H), 1.05-1. 35 (m, 6H).

Example 189 (General procedure 14) Methyl-phenyl-carbamic acid 3-phenylcarbamoyl-phenyl ester The title product was prepared from 3-hydroxy-N-phenyl-benzamide and N-methyl-N- phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC (54%, white solid). HPLC-MS: m/z = 347.2 (M+1); Rt: 4.01 min.

H NMR (CDCI3) : 7.76 (s, 1H), 7.68 (d, 1H), 7.58-7. 65 (m, 3H), 7.27-7. 51 (m, 8H), 7.15 (t, 1 H), 3.44 (s, 3H).

Example 190 (General procedure 14) Methyl-phenyl-carbamic acid quinolin-7-yl ester The title product was prepared from 7-hydroxyquinoline and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC (28%, white solid). HPLC- MS: m/z= 279.1 (M+1); Rt: 2.55 min.

1H NMR (CDC13) : 8. 93 (dd, 1H), 8.18 (d, 1H), 7.83-7. 86 (m, 1H), 7,82 (d, 1H), 7.35-7. 50 (m, 6H), 7.27-7. 32 (m, 1 H), 3.47 (s, 1 H).

Example 191 (General procedure 14) Methyl-phenyl-carbamic acid 4- (4-methyl-piperazine-1-carbonyl)-phenyl ester The title product was prepared from 1- (4-hydroxybenzoyl)-4-methyl-piperazine and N-methyl- N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC (22%, colorless oil). HPLC-MS: m/z= 354.1 (M+1) ; Rt : 2.07 min.

'H NMR (CDCI3) : 7.37-7. 49 (m, 4H), 7. 28-7. 37 (m, 3H), 7.16-7. 25 (m, 2H), 4.60-4. 00 (bs, 2H), 3.43 (s, 3H), 3.35-3. 90 (bs, 4H), 2.82 (s, 3H) 2.55-2. 90 (bs, 2H).

Example 192 (General procedure 14) Methyl-phenyl-carbamic acid 3-acetylamino-phenyl ester The title product was prepared from 3-acetamidophenol and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC (66%, white solid). HPLC- MS: m/z= 285.1 (M+1); Rt: 3.09 min.

H NMR (CDCI3) : 7.40-7. 49 (m, 1H), 7.31-7. 40 (m, 5H), 7.25-7. 30 (m, 1H), 7.22 (d, 1H), 7.14 (d, 1 H), 6-84 (bd, 1H), 3. 42 (s, 3H), 2.10 (s, 3H).

Example 193 (General procedure 14) Methyl-phenyl-carbamic acid 4-benzoyl-phenyl ester The title product was prepared from (4-hydroxy-phenyl)-phenyl-methanone and N-methyl-N- phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC (36%, col- orless oil). HPLC-MS: m/z= 332.2 (M+1); Rt: 4.42 min.

'H NMR (CDCI3) : 7.75-7. 85 (m, 4H), 7.58 (tt, 1H), 7.33-7. 52 (m, 6H), 7.27-7. 32 (m, 1H), 7.18- 7.25 (m, 2H), 3.44 (s, 3H).

Example 194 (General procedure 14) Methyl-phenyl-carbamic acid biphenyl-3-yl ester The title product was prepared from 3-phenylphenol and N-methyl-N-phenylcarbamoyl chlo- ride. The crude product was subjected to preparative HPLC (52%, colorless oil). HPLC-MS: m/z = 304.2 (M+1); Rt: 4.75 min.

'H NMR (CDCI3) : 7.52-7. 67 (m, 2H), 7.22-7. 52 (m, 11H), 7.03-7. 22 (m, 1H), 3.45 (s, 3H).

Example 195 (General procedure 14) Methyl-phenyl-carbamic acid 1 H-indol-4-yl ester The title product was prepared from 4-hydroxyindole and N-methyl-N-phenylcarbamoyl chlo- ride. The crude product was subjected to preparative HPLC (48%, off-white solid). HPLC- MS: m/z= 267.1 (M+1); Rt: 3.57 min.

'H NMR (CDCI3) : 8.20 (ds, 1H), 7.36-7. 50 (m, 4H), 7.17-7. 35 (m, 2H), 7.08-7. 17 (m, 2H), 6.94 (d, 1 H), 6.44 (s, 1 H), 3.48 (s, 3H).

Example 196 (General procedure 14) Methyl-phenyl-carbamic acid 5,6, 7, 8-tetrahydro-naphthalen-1-yl ester The title product was prepared from 5,6, 7, 8-tetrahydro-1-naphthol and N-methyl-N- phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC (42%, col- orless oil). HPLC-MS: m/z = 282.1 (M+1) ; Rt: 4.77 min.

'H NMR (CDC13) : 7.33-7. 45 (m, 4H), 7.22-7. 32 (m, 1H), 7.02-7. 13 (t, 1H), 6.82-7. 96 (m, 2H), 3.42 (s, 3H), 2.70-2. 82 (m, 2H), 2.50-2. 65 (m, 2H), 1.62-1. 83 (m, 4H).

Example 197 (General procedure 14) Methyl-phenyl-carbamic acid 5-oxo-5,6, 7, 8-tetrahydro-naphthalen-1-yl ester The title product was prepared from 5,6, 7, 8-tetrahydro-1-naphthol and N-methyl-N- phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC (60%, col- orless oil). HPLC-MS : m/z= 296.1 (M+1); Rt: 3.81 min.

1 NMR (CDCI3) : 7.91 (dd, 1 H), 7.21-7. 50 (m, 7H), 3.44 (s, 3H), 2.60-2. 93 (bs, 2H), 2.62 (t, 2H), 2.02-2. 20 (m, 2H).

Example 198 (General procedure 14) Methyl-phenyl-carbamic acid 1,3-dioxo-1, 3-dihydro-isobenzofuran-4-yl ester The title product was prepared from 4-hydroxy-isobenzofuran-1, 3-dione and N-methyl-N- phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC (50%, white solid). HPLC-MS: m/z = 298. 1 (M+1); Rt: 2.58 min, purity: 85%.

'H NMR (CDC13) : 7.90 (d, 1H), 7.48-7. 62 (m, 2H), 7.28-7. 45 (m, 5H), 3.38 (s, 3H).

Example 199 (General procedure 1) Methyl-phenyl-carbamic acid 4- (5-chloro-pyridin-2-yloxy)-phenyl ester The title product was prepared from 4- (5-chloro-pyridin-2-yloxy)-phenol and N-methyl-N- phenylcarbamoyl chloride. The crude product was subjected to column chromatography (ethyl acetate/heptane (1: 5) (85%, white solid). HPLC-MS: m/z= 355.1 (M+1); Rt : 4.56 min.

'H NMR (CDCl3) : 8.10 (d, 1H), 7.62 (dd, 1H), 7.31-7. 44 (m, 4H), 7.25-7. 30 (m, 1H), 7. 05-7. 20 (m, 4H), 6.84 (d, 1 H), 3.43 (s, 3H).

Example 200 (General procedure 14) (3-Fluoro-phenyl)-methyl-carbamic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester The title product was prepared from 4- (5-Trifluoromethyl-pyridin-2-yloxy)-phenol and 3-fluor- N-methylaniline. The crude product was subjected to preparative HPLC (31 %, white solid).

HPLC-MS: m/z = 407.0 (M+1); Rt: 4.93 min.

'H NMR (CDCI3) : 8.42 (s, 1H), 7.88 (dd, 1H), 7.36 (q, 1H), 7.07-7. 24 (m, 6H), 7.00 (d, 1H), 7.92-7. 05 (m, 1H), 3.44 (s, 3H).

Example 201 (General procedure 11) 4-Benzyl-piperazine-1-carboxylic acid 4- (5-chloro-pyridin-2-yloxy)-phenyl ester The title product was prepared from 4- (5-chloro-pyridin-2-yloxy)-phenol and 1- benzylpiperazine. The title product precipitated from the reaction mixture and was collected by filtration (88%, off-white solid). HPLC-MS: m/z = 424.1 (M+1); Rt: 2.91 min.

'H NMR (CDCI3) : 13.86 (bs, 1H), 8.11 (d, 1H), 7.60-7. 70 (m, 3H), 7.45-7. 55 (m, 3H), 7.05- 7.20 (m, 4H), 6.98 (d, 1H), 4. 26-4. 40 (m, 2H, 4. 15-4. 25 (m, 2H), 3.38-3. 53 (m, 2H), 3. 60-4. 15 (m, 2H), 2.72-2. 92 (m, 2H).

Example 202 (General procedure 11) 4-Pyridin-3-ylmethyl-piperazine-1-carboxylic acid 4- (5-chloro-pyridin-2-yloxy)-phenyl ester The title product was prepared from 4- (5-chloro-pyridin-2-yloxy)-phenol and (3- pyridylmethyl) piperazine. The title product precipitated from the reaction mixture and was col- lected by filtration and recrystallized from ethanol (35%, off-white solid). HPLC-MS: m/z = 425.2 (M+1); Rt: 2.39 min.

'H NMR (CDCl3) : 13.00-14. 50 (bs, 1H), 8.72 (d, 2H), 8.50 (bs, 1H), 8.11 (d, 1H), 7.64 (dd, 1H), 7.56 (bs, 1H), 7.06-7. 14 (m, 4H), 6.88 (d, 1H), 3. 6-4. 4 (m, 6H), 2.70-3. 50 (m, 4H).

Example 203 (General procedure 14) 4-Hydroxymethyl-piperidine-1-carboxylic acid 4- (5-chloro-pyridin-2-yloxy)-phenyl ester

The title product was prepared from 4- (5-chloro-pyridin-2-yloxy)-phenol and 4- hydroxymethyl-piperidine. The crude product was subjected to column chromatography (ethyl acetate/heptane, 1: 1) (75%, colorless oil). HPLC-MS: m/z= 363.1 (M+1); Rt: 3.58 min.

'H NMR (CDCI3) : 8.12 (d, 1H), 7.64 (dd, 1H), 7.05-7. 24 (m, 4H), 6.85 (d, 1H), 4.33 (ds, 2H), 3.56 (t, 2H), 2.75-3. 10 (m, 2H), 1.69-1. 95 (m, 3H), 1.56 (s, 1H), 1.19-1. 45 (m, 2H).

Example 204 (General procedure 1) Methyl-phenyl-carbamic acid 4-morpholin-4-yl-phenyl ester The title product was prepared from and 4-morpholin-4-yl-phenol and N-methyl-N- phenylcarbamoyl chloride. The crude product was extracted with dichloromethane from citric acid (5%). The combined organic phases were evaporated and the product crystallized from ethanol (22%, crystals). HPLC-MS: m/z= 313.2 (M+1); Rt: 3.75 min.

1H NMR (DMSO-d6): 7.35-7. 50 (m, 4H), 7.22-7. 32 (m, 1H), 7.00 (d, 2H), 6.92 (d, 2H), 3.72 (t, 4H), 3.32 (s, 3H), 3.05 (t, 4H).

Example 205 (General procedure 1) 1,4-Dioxa-8-aza-spiro [4.5] decane-8-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)- phenyl ester The title product was prepared from 4- (5-trifluoromethyl-pyridin)-2-yloxy)-phenol and 4- piperidone ethylene ketal. The crude product was extracted with dichloromethane from citric acid (5%). The combined organic phases were evaporated and the product crystallized from ethanol (61%, crystals). HPLC-MS: m/z = 425.2 (M+1) ; Rt: 4.45 min.

Example 206 (General procedure 14) The title product was prepared from 2- (4-hydroxy-phenyl)-indan-1, 3-dione and N-methyl-N- phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC (1 %, oil).

HPLC-MS : m/z= 372.1 (M+1); Rt: 4. 80 min.

Example 207 (General procedure 14) Methyl-phenyl-carbamic acid 4- (5, 6-dichloro-1, 3-dioxo-1, 3-dihydro-isoindol-2-yl)-phenyl ester The title product was prepared from 5, 6-dichloro-2- (4-hydroxy-phenyl)-isoindole-1, 3-dione

and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC (2%, ). HPLC-MS: m/z= 441.1 (M+1); Rt: 5.00 min.

Example 208 (General procedure 14) Methyl-phenyl-carbamic acid 4- (2-phenoxy-acetylamino)-phenyl ester The title product was prepared from N- (4-hydroxy-phenyl)-2-phenoxy-acetamide and N- methyl-N-phenylcarbamoyl chloride. The crude product was purified by preparative HPLC (54%, oil). HPLC-MS: m/z = 277.2 (M+1); Rt: 4.19 min.

Example 209 (General procedure 14) Methyl-phenyl-carbamic acid 4- [2- (4-chloro-phenyl)-ethyl]-phenyl ester The title product was prepared from 4- (4-chlorophenethyl)-phenol and N-methyl-N- phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC (57%, white crystals). HPLC-MS: m/z = 366.1 (M+1) ; Rt: 5.58 min.

'H NMR (CDCI3) : 7.31-7. 45 (m, 4H), 7.17-7. 30 (m, 3H), 6.96-7. 12 (m, 6H), 3.41 (s, 3H), 2.85 (s, 4H).

Example 210 (General procedure 14) Methyl-phenyl-carbamic acid 4-[(pyridine-2-carbonyl)-amino]-phenyl ester The title product was prepared from pyridine-2-carboxylic acid (4-hydroxy-phenyl)-amide and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC (41%,). HPLC-MS : m/z= 348.1 (M+1) ; Rt : 4.00 min.

'H NMR (CDCI3) : 7.32-7. 47 (m, 4H), 7.24-7. 31 (m, 3H), 7.10-7. 23 (m, 4H), 7.79 (d, 2H), 3.41 (m, 6H).

Example 211 (General procedure 14) Methyl-phenyl-carbamic acid 4-[methyl-(thiophene-2-carbonyl)-amino]-phenyl ester The title product was prepared from thiophene-2-carboxylic acid (4-hydroxy-phenyl)-methyl- amide and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC (16%, oil). HPLC-MS: m/z = 367.2 (M+1) ; Rt: 3.97 min.

Example 212 (General procedure 14) Methyl-phenyl-carbamic acid 4-butyrylamino-phenyl ester The title product was prepared from 4'-hydroxybutyranilide and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC (60%, white solid). HPLC- MS: m/z= 313.2 (M+1); Rt: 3.58 min.

Example 213 (General procedure 14) Methyl-phenyl-carbamic acid 4- (4, 6-dimethyl-pyrimidin-2-ylsulfanyl)-phenyl ester The title product was prepared from 4- (4, 6-dimethylpyrimidin-2-ylsulfanyl)-phenol and N- methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC (59%, white solid). HPLC-MS: m/z= 366.1 (M+1); Rt: 4.50 min.

'H NMR (CDCI3) : 7.59 (d, 2H), 7.32-7. 45 (m, 4H), 7.23-7. 31 (m, 1H), 7.16 (d, 2H), 6.68 (s, 1 H), 3.43 (s, 1 H), 2.32.

Example 214 (General procedure 14) Methyl-phenyl-carbamic acid 4-methanesulfonyl-phenyl ester The title product was prepared from 4-methylsulfonylphenol and N-methyl-N- phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC (50%, white solid). HPLC-MS: m/z = 306.1 (M+1); Rt: 3.22 min.

Example 215 (General procedure 14) Methyl-phenyl-carbamic acid 4- [2- (3-oxo-1, 2,3, 4-tetrahydro-quinoxalin-2-yl)-acetylamino]- phenyl ester The title product was prepared from N- (4-hydroxyphenyl)-2- (3-oxo-1, 2,3, 4-tetrahydro-2- quinoxalinyl) acetamide and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC (20%, yellow solid). HPLC-MS: m/z = 431.2 (M+1); Rt: 3.55 min.

Example 216 (General procedure 14) Methyl-phenyl-carbamic acid 4-phenylacetyl-phenyl ester

The title product was prepared from benzyl 4-hydroxyphenyl ketone and N-methyl-N- phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC (68%, light yellow oil). HPLC-MS: m/z = 431.2 (M+1); Rt: 3.55 min.

Example 217 (General procedure 12) 4-Benzoyl-piperidine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester The title product was prepared from 4- (5-trifluoromethyl-pyridin)-2-yloxy)-phenol and 4- benzoylpiperidine (29%, white solid). HPLC-MS: m/z = 471.3 (M+1); Rt: 5.12 min.

Example 218 (General procedure 11) [1,4'] Bipiperidinyl-1'-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester The title product was prepared from 4- (5-trifluoromethyl-pyridin)-2-yloxy)-phenol and 4- piperidinopiperidine. The crude product was filtered from the reaction mixture and washed with diethyl ether to give the title product (50%, off-white solid). HPLC-MS: m/z = 450.1 (M+1); Rt: 3. 12 min.

Example 219 (General procedure 12) 4-(2-Oxo-2, 3-dihydro-benzimidazol-1-yl)-piperidine-1-carboxylic acid 4- (5-trifluoromethyl- pyridin-2-yloxy)-phenyl ester The title product was prepared from 4- (5-Trifluoromethyl-pyridin-2-yloxy)-phenol and 1- piperidin-4-yl-1, 3-dihydro-benzoimidazol-2-one (44%, oil). HPLC-MS: m/z = 499.1 (M+1); Rt: 4.35 min.

1H NMR (CDCI3) : 10.15 (s, 1H), 8. 44 (s, 1H), 7.90 (dd, 1H), 7.23 (t, 1H), 7.13-7. 20 (m, 4H), 7.06-7. 13 (m, 2H), 7.02 (d, 1H), 4.40-4. 70 (m, 3H), 2.95-3. 30 (m, 2H), 2.40-2. 63 (m, 2H), 1.86 (d, 2H).

Example 220 (General procedure 12) 3-Diethylcarbamoyl-piperidine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester The title product was prepared from 4- (5-Trifluoromethyl-pyridin-2-yloxy)-phenol and N, N- diethyinipecotamide (56%, oil). HPLC-MS: m/z = 466.1 (M+1) ; Rt: 4.51 min.

Example 221 (General procedure 12) 4-Carbamoyl-piperidine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester The title product was prepared from 4- (5-Trifluoromethyl-pyridin-2-yloxy)-phenol and piperidine-4-carboxylic acid amide. The crude product was subjected to preparative HPLC (47%, white solid). HPLC-MS: mlz = 410.2 (M+1); Rt: 3.45 min.

Example 222 (General procedure 12) 3-Carbamoyl-piperidine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester The title product was prepared from 4- (5-Trifluoromethyl-pyridin-2-yloxy)-phenol and nipeco- tamide. The crude product was purified by preparative HPLC (60%, white solid). HPLC-MS: m/z = 410.2 (M+1); Rt: 3.45 min.

Example 223 (General procedure 14) Methyl-phenyl-carbamic acid 4- { [4- (methyl-phenyl-carbamoyloxy)-2-oxo-1, 2-dihydro- quinoline-3-carbonyl]-amino}-phenyl ester The title product was prepared from 4-hydroxy-2-oxo-1, 2-dihydro-quinoline-3-carboxylic acid (4-hydroxyphenyl)-amide and N-methyl-N-phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC (6.6 %, oil). HPLC-MS: m/z = 563.2 (M+1); Rt: 4.46 min.

1 NMR (CDCI3) : 8.38 (d, 1H), 7.75 (t, 1H), 7.35-7. 45 (m, 4H), 7.22-7. 34 (m, 1H), 7.14-7. 21 (t, 1H), 6.99-7. 15 (bs, 1H), 3.44 (s, 3H).

Example 224 (General procedure 14) Methyl-phenyl-carbamic acid 4- [ (4-hydroxy-2-oxo-1, 2-dihydro-quinoline-3-carbonyl)-amino]- phenyl ester The title product was prepared from 4-hydroxy-2-oxo-1, 2-dihydro-quinoline-3-carboxylic acid (4-hydroxy-phenyl)-amide and N-methyl-N-phenylcarbamoyl chloride (5%, ). HPLC-MS: m/z = 430.1 (M+1) ; Rt: 4.80 min, purity: 70%.

Example 225 (General procedure 14) Methyl-phenyl-carbamic acid 4- (4-hydroxy-benzyl)-phenyl ester

The title compound was prepared from 4, 4'-dihydroxydiphenylmethane and N-methyl-N- phenylcarbamoyl chloride. The crude product was subjected to preparative HPLC (21 %, white crystals which turn red after standing). HPLC-MS: m/z = 324.2 (M+1) ; Rt: 4.21 min.

Example 226 (General procedure 13) Methyl-phenyl-carbamic acid 4- (4-trifluoromethyl-benzylcarbamoyl)-phenyl ester The title product was prepared from 4- (methyl-phenyl-carbamoyloxy)-benzoic acid 2,5-dioxo- pyrrolidin-1-yl ester and 4-trifluoromethyl-benzylamine (94%, white crystals). HPLC-MS: m/z = 429. 2 (M+1); Rt: 4.35 min.

Example 227 (General procedure 13) Methyl-phenyl-carbamic acid 4- (butyl-methyl-carbamoyl)-phenyl ester The title product was prepared from 4- (methyl-phenyl-carbamoyloxy)-benzoic acid 2,5-dioxo- pyrrolidin-1-yl ester and n-butyl-methyl-amine. The crude product was subjected to prepara- tive HPLC (20%, oil). HPLC-MS: m/z= 341.2 (M+1); Rt: 3.96 min.

Example 228 (General procedure 13) Methyl-phenyl-carbamic acid 4- (methyl-phenethyl-carbamoyl)-phenyl ester The title product was prepared from 4- (methyl-phenyl-carbamoyloxy)-benzoic acid 2,5-dioxo- pyrrolidin-1-yl ester and methyl-phenethyl-amine. The crude product was subjected to prepa- rative HPLC (29 %, oil). HPLC-MS: m/z =389. 2 (M+1); Rt: 4.15 min.

Example 229 (General procedure 13) Methyl-phenyl-carbamic acid 4-[(pyridin-2-ylmethyl)-carbamoyl]-phenyl ester The title product was prepared from 4- (methyl-phenyl-carbamoyloxy)-benzoic acid 2,5-dioxo- pyrrolidin-1-yl ester and 2-aminomethylpyridine. The crude product was used without further purification (57%, oil). HPLC-MS: m/z = 362.2 (M+1); Rt: 2.43 min.

I H NMR (MeOH-d4) : 8.50 (d, 1H), 7.92 (d, 2H), 7.83 (dt, 1H), 7.38-7. 50 (m, 5H), 7.26-7. 37 (m, 2H), 7.15-7. 26 (m, 2H), 4.69 (s, 2H), 3.41 (s, 3H).

Example 230 (General procedure 13)

Methyl-phenyl-carbamic acid 4- (2-pyridin-2-yl-ethylcarbamoyl)-phenyl ester The title product was prepared from 4- (methyl-phenyl-carbamoyloxy)-benzoic acid 2,5-dioxo- pyrrolidin-1-yl ester and 2-aminoethylpyridine. The crude product was used without further purification (26%, oil). HPLC-MS: m/z = 376.2 (M+1); Rt : 2.25 min.

H NMR (MeOH-d4): 8. 51 (d, 1H), 7.87 (dt, 1H), 7.78 (d, 2H), 7.33-7. 50 m, 6H), 7.25-7. 33 (m, 1H), 7.18 (d, 2H), 3.74 (t, 2H), 3.41 (bs, 3H), 3.13 (t, 2H).

Example 231 (General procedure 13) Methyl-phenyl-carbamic acid 4- (2-phenylamino-ethylcarbamoyl)-phenyl ester The title product was prepared from 4- (methyl-phenyl-carbamoyloxy)-benzoic acid 2,5-dioxo- pyrrolidin-1-yl ester and N-phenylethylenediamine. The crude product was used without fur- ther purification (80%, off-white foam). HPLC-MS: m/z = 390.2 (M+1); Rt: 3.51 min.

'H NMR (MeOH-d4): 7.82 (d, 2H), 7.36-7. 48 (m, 4H), 7.22-7. 34 (m, 1H), 7.15-7. 22 (d, 2H), 7.10 (t, 2H), 6.69 (d, 2H), 6.62 (t, 1H), 3.72 (t, 2H), 3.57 (t, 2H), 3.40 (s, 3H), 3.20 (s, 1H).

Example 232 (General procedure 13) Methyl-phenyl-carbamic acid 4- (3-methyl-butylcarbamoyl)-phenyl ester The title product was prepared from 4- (methyl-phenyl-carbamoyloxy)-benzoic acid 2,5-dioxo- pyrrolidin-1-yl ester and iso-amylamine. The crude product was used without further purifica- tion (95%, oil). HPLC-MS: m/z= 341.2 (M+1); Rt : 3.99 min.

'H NMR (MeOH-d4): 7,82 (d, 2H), 7.36-7. 50 (m, 4H), 7. 26-7. 35 (m, 1H), 7.15-7. 24 (d, 2H), 3.34-3. 46 (m, 5H), 1.67 (sept, 1 H), 1.50 (q, 2H), 0.96 (d, 6H).

Example 233 (General procedure 13) Methyl-phenyl-carbamic acid 4- (3, 3-dimethyl-butylcarbamoyl)-phenyl ester The title product was prepared from 4- (methyl-phenyl-carbamoyloxy)-benzoic acid 2,5-dioxo- pyrrolidin-1-yl ester and 3, 3-dimethylbutylamine. The crude product was used without further purification (88%, oil). HPLC-MS: m/z= 355.1 (M+1) ; Rt : 3.10 min.

1H NMR (MeOH-d4): 7.82 (d, 2H), 7.36-7. 50 (m, 4H), 7.25-7. 35 (m, 1H), 7.15-7. 25 (d, 2H), 3.33-3. 47 (m, 5H), 1.49-1. 57 (m, 2H), 0.97 (s, 9H).

Example 234 (General procedure 13) Methyl-phenyl-carbamic acid 4-[(tetrahydro-furan-2-ylmethyl)-carbamoyl]-phenyl ester The title product was prepared from 4- (methyl-phenyl-carbamoyloxy)-benzoic acid 2,5-dioxo- pyrrolidin-1-yl ester and C- (tetrahydro-furan-2-yl) methylamine. The crude product was used without further purification (86%, oil). HPLC-MS: m/z = (M+1); Rt: min.

'H NMR (MeOH-d4): 7.84 (d, 2H), 7.35-7. 50 (m, 4H), 7.25-7. 35 (m, 1H), 7.12-7. 25 (d, 2H), 4.10 (qui, 1H), 3.87 (q, 1H), 3.68-3. 82 (m, 1H), 3.41 (s, 3H), 3.35-3. 54 (m, 2H), 1.82-2. 10 (m, 3H), 1.58-1. 72 (m, 1H).

Example 235 (General procedure 13) Methyl-phenyl-carbamic acid 4-cyclohexylcarbamoyl-phenyl ester The title product was prepared from 4- (methyl-phenyl-carbamoyloxy)-benzoic acid 2,5-dioxo- pyrrolidin-1-yl ester and cyclohexylamine. The crude product was used without further purifi- cation (79%, off-white crystals). HPLC-MS: m/z = 353.2 (M+1); Rt: 3.98 min.

1 NMR (MeOH-d4): 8.18 (d, 1H), 7.85 (d, 2H), 7.36-7. 52 (m, 4H), 7.25-7. 33 (m, 1H), 7.20 (d, 2H), 3.74 (m, 1 H), 1.77-1. 88 (m, 2H), 1.65-1. 77 (m, 2H), 1.60 (d, 1 H), 1.24-1. 40 (m, 4H), 1- 07-1.23 (m, 1H).

Example 236 (General procedure 13) Methyl-phenyl-carbamic acid 4-cyclopropylcarbamoyl-phenyl ester The title product was prepared from 4- (methyl-phenyl-carbamoyloxy)-benzoic acid 2,5-dioxo- pyrrolidin-1-yl ester and cyclopropylamine. The crude product was used without further purifi- cation (97%, oil). HPLC-MS: m/z = 311.2 (M+1); Rt : 3.21 min.

1H NMR (MeOH-d4): 7.81 (d, 2H), 7.36-7. 50 (m, 4H), 7.25-7. 36 (m, 1H), 7. 18 (d, 2H), 3.40 (bs, 3H), 2.78-2. 87 (m, 1 H), 0.75-0. 85 (m, 2H), 0.57-0. 65 (m, 2H).

Example 237 (General procedure 13) Methyl-phenyl-carbamic acid 4- (cyclohexylmethyl-carbamoyl)-phenyl ester The title product was prepared from 4- (methyl-phenyl-carbamoyloxy)-benzoic acid 2,5-dioxo- pyrrolidin-1-yl ester and C-cyclohexyl-methylamine. The crude product was used without fur- ther purification (84%, oil). HPLC-MS: m/z = 367.3 (M+1); Rt: 4.28 min.

'H NMR (MeOH-d4): 7.81 (d, 2H), 7.36-7. 49 (m, 4H), 7.25-7. 32 (m, 1H), 7.19 (d, 2H), 3.40 (bs, 3H), 3.20 (d, 2H), 1.55-1. 82 (m, 5H), 1.13-1. 35 (m, 4H), 0.90-1. 10 (m, 2H).

Example 238 Methyl-phenyl-carbamic acid 5-nitro-pyridin-2-yl ester A solution of 2-hydroxy-5-nitropyridine (1.40 g, 10.0 mmol), 1-methyl-3- (methyl-phenyl- carbamoyl)-3H-imidazol-1-ium iodide (3.43 g, 10.0 mmol) and triethylamine (0.42 ml, 10.0 mmol) in acetonitrile (25 ml) was heated at 50 °C for 5 h. The solvent was evaporated in vacuo and the residue was purified by flash column chromatography (SiO2, ethyl acetate:- heptane (25: 75) ) followed by crystallisation from ethyl acetate: heptane yielding the title com- pound (1.13 g, 41% yield) as a white solid. oh NMR (300MHz, CDCI3) : 3 3. 44 (br. s, 3H), 7.17 (br. d, 1H), 7.27-7. 45 (m, 5H), 8.49 (br. d, 1 H), 9.19 (br. s, 1 H) ; HPLC-MS (Method A): m/z = 296 (M+Na); Rt = 3.45 min.

Example 239 Methyl-phenyl-carbamic acid pyrimidin-2-yl ester A solution of 2-hydroxypyrimidine hydrochloride (0.40 g, 3.00 mmol), 1-methyl-3- (methyl- phenyl-carbamoyl)-3H-imidazol-1-ium iodide (1.03 g, 3.00 mmol) and triethylamine (0.83 ml, 6.00 mmol) in acetonitrile (15 ml) was stirred at room temperature overnight. The solvent was evaporated in vacuo and the residue was purified by flash column chromatography (Si02, ethyl acetate) followed by crystallisation from ethyl acetate: heptane yielding the title com- pound (0.08 g, 12% yield) as a white solid.

'H NMR (300MHz, CDCI3) : 63. 43 (br. s, 3H), 7.14-7. 31 (m, 2H), 7.39 (m, 4H), 8.68 (d, 2H); HPLC-MS (Method A): m/z = 252 (M+Na); Rt = 2.32 min.

Example 240 Methyl-phenyl-carbamic acid 7-chloro-quinolin-4-yl ester A solution of 7-chloro-4-hydroxyquinoline (0.54 g, 3.00 mmol), 1-methyl-3- (methyl-phenyl- carbamoyl)-3H-imidazol-1-ium iodide (1.03 g, 3.00 mmol) and triethylamine (0.42 ml, 3.00 mmol) in acetonitrile (15 ml) was stirred at room temperature for 18 hours. The solvent was evaporated in vacuo and the residue was purified by flash column chromatography (Si02, ethyl acetate: heptane (40: 60) ) yielding the title compound (0.87 g, 93% yield) as a colourless

oil which solidified upon standing.

'H NMR (300MHz, Ceci3) : 83. 47 (br. s, 3H), 7.28-7. 58 (m, 8H), 8.05 (br. s, 1H), 8.85 (d, 1H) ; HPLC-MS (Method A): m/z = 313 (M+H); Rt = 3.79 min.

Example 241 Methyl-phenyl-carbamic acid quinolin-4-yl ester A mixture of 4-hydroxyquinoline (0. 44 g, 3.00 mmol)), 1-methyl-3- (methyl-phenyl- carbamoyl)-3H-imidazol-1-ium iodide (1.03 g, 3.00 mmol) and triethylamine (0.42 mi, 3.00 mmol) in acetonitrile (15 ml) was stirred at room temperature for 18 hours. The solvent was evaporated in vacuo and the residue was purified by flash column chromatography (SiO2, ethyl acetate: heptane (50: 50) ) yielding the title compound (0.75 g, 90% yield) as a white solid.

'H NMR (300MHz, CDCI3) : 63. 49 (br. s, 3H), 7.37 (br. t, 1H), 7.41-7. 62 (m, 7H), 7.69 (br. t, 1 H), 8.08 (br. d, 1 H), 8.87 (d, 1 H) ; HPLC-MS (Method A): m/z = 279 (M+H); Rt = 2.56 min.

Example 242 Methyl-phenyl-carbamic acid 5-methyl-isoxazol-3-yl ester A mixture of 3-hydroxy-5-methylisoxazole (0.30 g, 3.00 mmol)), 1-methyl-3- (methyl-phenyl- carbamoyl)-3H-imidazol-1-ium iodide (1.03 g, 3.00 mmol) and triethylamine (0.42 ml, 3.00 mmol) in acetonitrile (15 mi) was stirred at room temperature for 18 hours. The solvent was evaporated in vacuo and the residue was purified by flash column chromatography (SiO2, ethyl acetate: heptane (25: 75) ) yielding the title compound (0.67 g, 96% yield) as a colourless oil.

'H NMR (300 MHz, CDCI3) : 82. 40 (s, 3H), 3.40 (br. s, 3H), 6.14 (br. s, 1H), 7. 28-7. 44 (m, 5H); HPLC-MS (Method A): m/z = 255 (M+Na); Rt = 3.31 min.

Example 243 Methyl-phenyl-carbamic acid quinoxalin-2-yl ester A mixture of 2-hydroxyquinoxaline (0. 44 g, 3.00 mmol)), 1-methyl-3- (methyl-phenyl- carbamoyl)-3H-imidazol-1-ium iodide (1.03 g, 3.00 mmol) and triethylamine (0.42 ml, 3.00 mmol) in acetonitrile (15 mi) was stirred at room temperature for 18 hours followed by heat- ing at 40 °C for 24 hours. The solvent was evaporated in vacuo and the residue was purified

by flash column chromatography (Si02, ethyl acetate: heptane (30: 70) ) yielding the title com- pound (0.65 g, 77% yield) as a white solid.

'H NMR (300 MHz, CDCI3) : 63. 48 (br. s, 3H), 7.29 (m, 1 H), 7.41 (m, 4H), 7.72 (m, 2H), 8.00 (m, 1H), 8.10 (m, 1H), 8.67 (br. s, 1H) ; HPLC-MS (Method A): m/z= 280 (M+H); Rt = 3.66 min.

Example 244 Methyl-phenyl-carbamic acid 4-methyl-quinolin-2-yl ester A mixture of 2-hydroxy-4-methylquinoline (0.48 g, 3.00 mmol)), 1-methyl-3- (methyl-phenyl- carbamoyl)-3H-imidazol-1-ium iodide (1.03 g, 3.00 mmol) and triethylamine (0.42 ml, 3.00 mmol) in acetonitrile (15 ml) was stirred at room temperature for 18 hours followed by heat- ing at 50 °C for 4 days. The solvent was evaporated in vacuo and the residue was purified by flash column chromatography (SiO2, ethyl acetate: heptane (30: 70) ) yielding the title com- pound (0.24 g, 27% yield) as a white solid.

'H NMR (300 MHz, CDCI3) : 8 2. 70 (s, 3H), 3.49 (br. s, 3H), 7.08 (m, 1H), 7.27 (m, 1H), 7.40 (m, 4H), 7.53 (t, 1 H), 7.69 (t, 1 H), 7.96 (d, 1 H), 8.00 (d, 1 H) ; HPLC-MS (Method A): m/z = 293 (M+H); Rt = 3.88 min.

Example 245 Methyl-phenyl-carbamic acid 3-methyl-quinoxalin-2-yl ester A mixture of 2-hydroxy-3-methylquinoxaline (0.48 g, 3.00 mmol)), 1-methyl-3- (methyl- phenyl-carbamoyl)-3H-imidazol-1-ium iodide (1.03 g, 3.00 mmol) and triethylamine (0.42 ml, 3.00 mmol) in acetonitrile (15 mi) was stirred at room temperature for 18 hours followed by heating at 50 °C for 3 days. The solvent was evaporated in vacuo and the residue was puri- fied by flash column chromatography (Si02, ethyl acetate: heptane (50: 50) ) yielding the title compound (0.59 g, 67% yield) as a white solid.

'H NMR (300 MHz, CDCI3) : 2. 61 (br. s, 3H), 3.48 (br. s, 3H), 7.30 (m, 1H), 7.42 (m, 4H), 7.69 (m, 2H), 7.99 (m, 2H); HPLC-MS (Method A): m/z = 294 (M+H); Rt = 3.92 min.

Example 246 Methyl-phenyl-carbamic acid 4, 6-dimethyl-pyrimidin-2-yl ester A solution of 4, 6-dimethyl-2-hydroxypyrimidine (0.37 g, 3.00 mmol)), 1-methyl-3- (methyl-

phenyl-carbamoyl)-3H-imidazol-1-ium iodide (1.03 g, 3.00 mmol) and triethylamine (0.42 ml, 3.00 mmol) in acetonitrile (15 ml) was stirred at room temperature for 18 hours. The solvent was evaporated in vacuo and the residue was purified by flash column chromatography (SiO2, ethyl acetate: heptane (50: 50) ) yielding the title compound (0.46 g, 60% yield) as a white solid.

'H NMR (300 MHz, CDCI3) : #2. 48 (s, 6H), 3.43 (br. s, 3H), 6.92 (br. s, 1H), 7.22 (m, 1H), 7.37 (m, 4H); HPLC-MS (Method A): m/z = 258 (M+H); Rt = 2.77 min.

Example 247 Methyl-phenyl-carbamic acid isoquinolin-6-yl ester A solution of 6-hydroxyquinoline (0.44 g, 3.00 mmol), 1-methyl-3- (methyl-phenyl-carbamoyl)- 3H-imidazol-1-ium iodide (1.03 g, 3.00 mmol) and triethylamine (0.42 ml, 3.00 mmol) in ace- tonitrile (15 mi) was stirred at room temperature for 18 hours. The solvent was evaporated in vacuo and the residue was purified by flash column chromatography (SiO2, ethyl ace- tate: heptane (50: 50) ) yielding the title compound (0.80 g, 96% yield) as a white solid.

'H NMR (300MHz, CDCI3) : 5 3. 47 (s, 3H), 7.28 (m, 1H), 7.33-7. 54 (m, 6H), 7.59 (s, 1H), 8.08 (d, 2H), 8.86 (m, 1 H) ; HPLC-MS (Method A): m/z = 279 (M+H); Rt = 2.63 min.

Example 248 Methyl-phenyl-carbamic acid quinolin-2-yl ester A solution of 2-hydroxyquinoline (0.44 g, 3.00 mmol), 1-methyl-3- (methyl-phenyl-carbamoyl)- 3H-imidazol-1-ium iodide (1.03 g, 3.00 mmol) and triethylamine (0.42 mi, 3.00 mmol) in ace- tonitrile (15 ml) was stirred at room temperature for 18 hours. More acetonitrile (60 ml) was added and the solution was heated at 50 °C for 3 days. The solvent was evaporated in vacuo and the residue was purified by flash column chromatography (Si02, ethyl acetate: heptane (40: 60) ) yielding the title compound (0.33 g, 40% yield) as a white solid.

'H NMR (300MHz, Ceci3) : 63. 50 (br. s, 3H), 7.14-7. 30 (m, 2H), 7.42 (m, 4H), 7.52 (t, 1H), 7.71 (t, 1H), 7.82 (d, 1H), 8.00 (d, 1H), 8.19 (d, 1H) ; HPLC-MS (Method A): m/z = 279 (M+H); Rt = 3.91 min.

Example 249 Methyl-phenyl-carbamic acid isoquinolin-3-yl ester

A solution of 3-hydroxyisoquinoline (0. 44 g, 3.00 mmol), 1-methyl-3- (methyl-phenyl- carbamoyl)-3H-imidazol-1-ium iodide (1.03 g, 3.00 mmol) and triethylamine (0.42 mi, 3.00 mmol) in acetonitrile (15 mi) was stirred at room temperature for 18 hours. The solvent was evaporated in vacuo and the residue was purified by flash column chromatography (Si02, ethyl acetate: heptane (50: 50) ) yielding the title compound (0.82 g, 99% yield) as a white solid.

'H NMR (300MHz, CDCI3) : 8 3. 49 (br. s, 3H), 7.24 (m, 1H), 7.33-7. 47 (m, 5H), 7.51 (t, 1H), 7.63 (t, 1 H), 7.77 (d, 1 H), 7.94 (d, 1 H), 9.06 (s, 1 H) ; HPLC-MS (Method A): m/z = 279 (M+H); Rt = 3.68 min.

Example 250 Methyl-phenyl-carbamic acid 4-trifluoromethyl-pyrimidin-2-yl ester A solution of 4- (trifluoromethyl)-2-pyrimidol (0.49 g, 3.00 mmol), 1-methyl-3- (methyl-phenyl- carbamoyl)-3H-imidazol-1-ium iodide (1.03 g, 3.00 mmol) and triethylamine (0.42 mi, 3.00 mmol) in acetonitrile (15 mi) was stirred at room temperature for 3 days. The solvent was evaporated in vacuo and the residue was purified by flash column chromatography (SiO2, ethyl acetate: heptane (30: 70) ) yielding the title compound (0.35 g, 39% yield) as a colourless oil.

'H NMR (300MHz, CDCI3) : 63. 45 (br. s, 3H), 7.28 (m, 1H), 7.38 (m, 4H), 7.52 (br. s, 1H), 8.93 (br. s, 1 H) ; HPLC-MS (Method A): m/z = 320 (M+Na); Rt = 3.58 min.

Example 251 Morpholine-4-carboxylic acid 4-trifluoromethyl-pyrimidin-2-yl ester A solution of 4- (trifluoromethyl)-2-pyrimidol (0.49 g, 3.00 mmol), 4-morpholinecarbonyl chlo- ride (0.45 g, 3.00 mmol) and 1, 4-diazabicyclo [2.2. 2octane (0.51 g, 3.00 mmol) in N, N- dimethylformamide (15 ml) was stirred at room temperature for 2 hours. Water was added and the solution was extracted twice with dichloromethane. The combined organic layers were dried over sodium sulphate, filtered and evaporated in vacuo. The residue was purified by flash column chromatography (Si02, ethyl acetate: heptane (30: 70-50 : 50)) yielding the title compound (0.66 g, 80% yield) as a white solid.

'H NMR (300MHz, CDC13) : 63. 57-3. 81 (m, 8H), 7.57 (d, 1H), 8.97 (d, 1H). ; HPLC-MS (Method A): m/z = 300 (M+Na); Rt = 2.36 min.

Example 252 Methyl-phenyl-carbamic acid 3-nitro-pyridin-2-yl ester A solution of 2-hydroxy-3-nitropyridine (0.42 g, 3.00 mmol), 1-methyl-3- (methyl-phenyl- carbamoyl)-3H-imidazol-1-ium iodide (1.03 g, 3.00 mmol) and triethylamine (0.42 mi, 3.00 mmol) in acetonitrile (15 ml) was stirred at room temperature for 3 days. The solvent was evaporated in vacuo and the residue was purified by flash column chromatography (SiO2, ethyl acetate: heptane (40: 60) ) yielding the title compound (0.41 g, 50% yield) as a yellow solid.

'H NMR (300MHz, CDCI3) : #3. 41 + 3.58 (2 x br. s, 3H), 7.30 (m, 1H), 7.42 (m, 5H), 8.45 (br. d, 1 H), 8.49 (br. s, 1 H) ; HPLC-MS (Method A): m/z = 296 (M+Na); Rt = 3.22 min.

Example 253 Methyl-phenyl-carbamic acid 5-chloro-pyridin-2-yl ester A solution of 5-chloro-2-pyridol (0.39 g, 3.00 mmol), 1-methyl-3- (methyl-phenyl-carbamoyl)- 3H-imidazol-1-ium iodide (1.03 g, 3.00 mmol) and triethylamine (0.42 ml, 3.00 mmol) in ace- tonitrile (15 mi) was stirred at room temperature for 3 days. The solvent was evaporated in vacuo and the residue was purified by flash column chromatography (SiO2, ethyl ace- tate: heptane (30: 70) ) yielding the title compound (0.78 g, 99% yield) as a white solid.

'H NMR (300MHz, CDCI3) : 63. 44 (br. s, 3H), 7.00 (br. s, 1H), 7.27 (m, 1H), 7.39 (m, 4H), 7.69 (d, 1 H), 8.30 (d, 1 H) ; HPLC-MS (Method A): m/z = 285 (M+Na); Rt = 3.47 min.

Example 254 Methyl-phenyl-carbamic acid 5-(2-nitro-phenyl)-pyrimidin-2-yl ester A solution of 5- (2-nitrophenyl)-pyrimidin-2-ol (0.35 g, 1.61 mmol), 1-methyl-3- (methyl-phenyl- carbamoyl)-3H-imidazol-1-ium iodide (0.55 g, 1.61 mmol) and triethylamine (0.22 ml, 1.61 mmol) in acetonitrile (15 ml) was heated at 50 °C for 18 hours. The solvent was evaporated in vacuo and the residue was purified by flash column chromatography (SiO2, ethyl ace- tate: heptane (50: 50) ) yielding the title compound (0.18 g, 32% yield) as a yellow oil.

1H NMR (300MHz, CDCI3) : 15 3. 47 (br. s, 3H), 7.29 (m, 1H), 7.40 (m, 5H), 7.63 (dt, 1H), 7.72 (dt, 1H), 8. 10 (d, 1H), 8.61 (br. s, 2H); HPLC-MS (Method A): m/z= 351 (M+H), 373 (M+Na), 723 (2M+Na).; Rt = 3.65 min.

Example 255 Methyl-phenyl-carbamic acid 5-trifluoromethyl-pyridin-2-yl ester A solution of 2-hydroxy-5- (trifluoromethyl) pyridine (0.49 g, 3.00 mmol), 1-methyl-3- (methyl- phenyl-carbamoyl)-3H-imidazol-1-ium iodide (1.03 g, 3.00 mmol) and triethylamine (0.42 ml, 3.00 mmol) in acetonitrile (15 ml) was stirred at room temperature for 18 hours. The solvent was evaporated in vacuo and the residue was purified by flash column chromatography (SiO2, ethyl acetate: heptane (15: 85) ) yielding the title compound (0.59 g, 66% yield) as a white solid.

'H NMR (300MHz, CDCI3) : 63. 43 (br. s, 3H), 7.23 (br. s, 1H), 7.28 (m, 1H), 7. 37 (m, 4H), 7.94 (br. d, 1 H), 8.62 (br. s, 1 H) ; HPLC-MS (Method A): m/z = 319 (M+Na); Rt = 3.85 min.

Example 256 Methyl-phenyl-carbamic acid 3-chloro-5-trifluoromethyl-pyridin-2-yl ester A solution of 3-chloro-5- (trifluoromethyl)-2-pyridinol (0.59 g, 3.00 mmol), 1-methyl-3- (methyl- phenyl-carbamoyl)-3H-imidazol-1-ium iodide (1.03 g, 3.00 mmol) and triethylamine (0. 42 ml, 3.00 mmol) in acetonitrile (15 mi) was stirred at room temperature for 18 hours. The solvent was evaporated in vacuo and the residue was purified by flash column chromatography (SiO2, ethyl acetate: heptane (15: 85) ) yielding the title compound (146 mg, 15% yield) as a white solid.

'H NMR (300MHz, CDCI3) : 63. 43 (br. s, 3H), 7.30 (m, 1H), 7.40 (d, 4H), 8.00 (br. s, 1H), 8.52 (br. s, 1 H). ; HPLC-MS (Method A): mlz = 353 (M+Na); Rt = 4.29 min.

Example 257 Methyl-phenyl-carbamic acid 5-nitro-3-trifluoromethyl-pyridin-2-yl ester A solution of 2-hydroxy-5-nitro-3- (trifluoromethyl) pyridine (0.36 g, 1.73 mmol), N-methyl-N- phenylcarbamoyl chloride (0.44 g, 2.59 mmol) and 1, 4-diazabicyclo [2.2. 2] octane (0.29 g, 2.59 mmol) in tetrahydrofuran (15 ml) was stirred at room temperature for 18 hours. The sol- vent was evaporated in vacuo and the residue was purified by flash column chromatography (SiO2, ethyl acetate: heptane (15: 85) ) yielding the title compound (0.55 g, 92% yield) as an orange solid.

'H NMR (300MHz, CDCI3) : 63. 46 (br. s, 3H), 7.23-7. 46 (m, 5H), 8.70 (br. s, 1H), 9.37 (br. s, 1 H) ; HPLC-MS (Method A): m/z = 364 (M+H); Rt = 4.08 min.

Example 258 (3-Chloro-phenyl)-methyl-carbamic acid 4-trifluoromethyl-pyrimidin-2-yl ester At 0 °C diphosgene (0.99 g, 5.00 mmol) was added to a stirred solution of 4-trifluoromethyl-2- hydroxypyrimidine (1.64 g, 10.0 mmol) in tetrahydrofuran (25 ml). The cooling bath was re- moved and stirring was continued at room temperature for 1 hour. (3-Chlorophenyl)- methylamine (0.35 g, 2.50 mmol) was added to one-fourth of the solution. After stirring over- night at room temperature the solvent was evaporated in vacuo and the residue was purified by flash column chromatography (Si02, ethyl acetate: heptane (20: 80) ) followed by prepara- tive HPLC, yielding the title compound (332 mg, 40%) as a colourless oil. oh NMR (300MHz, CDCI3) : 63. 45 (br. s, 3H), 7.23-7. 44 (m, 4H), 7.56 (d, 1H), 8.94 (d, 1H) ; HPLC-MS (Method A): m/z = 354 (M+H); Rt = 4.03 min.

Example 259 Methyl-m-tolyl-carbamic acid 4-trifluoromethyl-pyrimidin-2-yl ester At 0 °C diphosgene (0.99 g, 5.00 mmol) was added to a stirred solution of 4-trifluoromethyl-2- hydroxypyrimidine (1.64 g, 10.0 mmol) in tetrahydrofuran (25 ml). The cooling bath was re- moved and stirring was continued at room temperature for 1 hour. Methyl-m-tolyl-amine (0.30 g, 2.50 mmol) was added to one-fourth of the solution. After stirring overnight at room tem- perature the solvent was evaporated in vacuo and the residue was purified by flash column chromatography (SiO2, ethyl acetate: heptane (20: 80) ) followed by preparative HPLC, yielding the title compound (51 mg, 7%) as a colourless oil.

'H NMR (300MHz, CDCI3) : 82. 37 (s, 3H), 3.42 (br. s, 3H), 7.07-7. 31 (m, 4H), 7.52 (br. s, 1H), 8.92 (br. s, 1 H) ; HPLC-MS (Method A): m/z = 334 (M+Na); Rt = 3.92 min.

Example 260 Morpholine-4-carboxylic acid 4-trifluoromethyl-pyrimidin-2-yl ester A solution of 4-trifluoromethyl-2-hydroxypyrimidine (0.49 g, 3.00 mmol), 4- morpholinecarbonyl chloride (0.45 g, 3.00 mmol) and 1, 4-diazabicyclo [2.2. 2] octane (0.34 g, 3.00 mmol) in dimethylformamide (15 ml) was stirred at room temperature for 1 hour. Water and brine were added and the solution was extracted twice with dichloromethane. The com- bined organic layers were dried over sodium sulphate, filtered and evaporated in vacuo. The

residue was purified by flash column chromatography (Si02, ethyl acetate: heptane (30: 70 50: 50) ) yielding the title compound (0.66 g, 80% yield) as a white solid.

'H NMR (300MHz, CDCl3) : 63. 45 (br. s, 3H), 7.23-7. 44 (m, 4H), 7.56 (d, 1H), 8.94 (d, 1H) ; HPLC-MS (Method A): m/z = 354 (M+H); Rt = 4.03 min.

Example 261 Methyl-phenyl-carbamic acid 4, 5-dichloro-pyridazin-3-yl ester A solution of 4, 5-dichloro-3-hydroxypyridazine (0.49 g, 3.00 mmol), N-methyl-N- phenylcarbamoyl chloride (0.51 g, 3.00 mmol) and triethylamine (0.42 ml, 3.00 mmol) in tet- rahydrofuran (15 ml) was stirred at room temperature for 3 days. The solvent was evapo- rated in vacuo and the residue was purified by flash column chromatography (SiO2, ethyl acetate: heptane (20: 80) ) yielding the title compound (0.12 g, 14% yield) as a white solid.

'H NMR (300MHz, CDC13) : 3. 50 (s, 3H), 7.18-7. 32 (m, 5H), 7.63 (s, 1H) ; HPLC-MS (Method A): m/z = 320 (M+Na); Rt = 2.91 min.

Example 262 Methyl-phenyl-carbamic acid 5-benzoylamino-pyridin-2-yl ester A solution of N-(6-hydroxy-pyridin-3-yl)-benzamide (0.64 g, 3.00 mmol), N-methyl-N- phenylcarbamoyl chloride (0.51 g, 3.00 mmol) and 1, 4-diazabicyclo [2.2. 2] octane (0.34 g, 3.00 mmol) in dimethylformamide (15 mi) was stirred at room temperature for 1 hour. Water was added and the precipitates were collected by suction. The solids were dissolved in di- chloromethane and the solution was dried over sodium sulphate, filtered and evaporated in vacuo. The residue was dissolved in ethyl acetate and filtered over a short pad of silica.

Evaporation of the solvent in vacuo yielded the title compound (0.70 g, 68% yield) as a thick oil.

'H NMR (300MHz, CDCI3) : 63. 40 (br. s, 3H), 6.90 (br. s, 1H), 7.26 (m, 1H), 7.31-7. 44 (m, 6H), 7.50 (m, 1 H), 7.88 (d, 2H), 8.08 (dd, 1 H), 8.37 (d, 1 H), 8.79 (br. s, 1 H) ; HPLC-MS (Method A): m/z = 348 (M+H); Rt = 3.49 min.

Example 263 Methyl-phenyl-carbamic acid 5-(cyclohexanecarbonyl-amino)-pyridin-2-yl ester A solution of cyclohexanecarboxylic acid (6-hydroxy-pyridin-3-yi)-amide (0.66 g, 3.00 mmol),

N-methyl-N-phenylcarbamoyl chloride (0.51 g, 3.00 mmol) and 1, 4-diazabicyclo [2.2. 2] octane (0.34 g, 3.00 mmol) in dimethylformamide (20 ml) was stirred at room temperature for 18 hours. Water was added and the precipitates were collected by suction. The solids were dis- solved in dichloromethane and the solution was dried over sodium sulphate, filtered and evaporated in vacuo. The residue was crystallised from ethyl acetate: heptane yielding the title compound (0.75 g, 71 % yield) as a slightly coloured solid.

'H NMR (300MHz, CDCI3) : 81. 18-1.33 (m, 3H), 1.42-1. 59 (m, 2H), 1.60 (m, 1H), 1.77-1. 94 (m, 4H), 2.20 (m, 1 H), 3.45 (br. s, 3H), 6.91 (br. s, 1 H), 7.28 (m, 1 H), 7.39 (m, 4H), 7.94 (br. s, 1 H), 8.00 (dd, 1 H), 8.20 (d, 1 H) ; HPLC-MS (Method A): m/z = 354 (M+H); Rt = 3.74 min.

Example 264 Methyl-phenyl-carbamic acid 4, 4-dimethyl-2, 6-dioxo-3, 4,5, 6-tetrahydro-2H- [1, 3'] bipyridinyl-6'- yl ester A solution of 6'-hydroxy-4, 4-dimethyl-4, 5-dihydro-3H- 1, 3'] bipyridinyl-2, 6-dione (0.70 g, 3.00 mmol), N-methyl-N-phenylcarbamoyl chloride (0.51 g, 3.00 mmol) and 1,4-diazabi- cyclo [2.2. 2] octane (0.34 g, 3.00 mmol) in dimethylformamide (20 ml) was stirred at room temperature for 18 hours. Water was added and the precipitates were collected by suction and subsequently dried in a vacuum oven yielding the title compound (0.75 g, 71% yield) as a white solid.

'H NMR (300MHz, CDCI3) : 61. 20 (s, 6H), 2. 68 (s, 4H), 3.44 (br. s, 3H), 7.14 (br. s, 1H), 7.25 (m, 1 H), 7.37 (m, 4H), 7.48 (br. d, 1 H), 8.08 (d, 1 H) ; HPLC-MS (Method A): m/z= 368 (M+H); Rt = 3.41 min.

Example 265 Methyl-phenyl-carbamic acid 5-(2, 2-dimethyl-propionylamino)-pyridin-2-yl ester A solution of N- (6-hydroxy-pyridin-3-yl)-2, 2-dimethyl-propionamide (0.58 g, 3.00 mmol), N- methyl-N-phenylcarbamoyl chloride (0.51 g, 3.00 mmol) and 1, 4-diazabicyclo [2.2. 2] octane (0.34 g, 3.00 mmol) in dimethylformamide (20 mi) was stirred at room temperature for 1 hour.

Water was added and a thick oil was being formed. The water was decanted and the residue was dissolved in dichloromethane. The solution was dried over sodium sulphate, filtered and evaporated in vacuo yielding the title compound (0.55 g, 56% yield) as a brown oil that solidi- fied upon standing.

'H NMR (300MHz, CDC13) : 61. 29 (s, 9H), 3.43 (br. s, 3H), 6.97 (br. s, 1H), 7.26 (m, 1H), 7.38

(m, 4H), 7.64 (br. s, 1H), 8.10 (dd, 1H), 8.28 (br. s, 1H) ; HPLC-MS (Method A): m/z= 348 (M+H); Rt = 3. 49 min.

Example 266 Methyl-phenyl-carbamic acid 5- (2-cyclohexyl-acetylamino)-pyridin-2-yl ester A solution of 2-cyclohexyl-N-(6-hydroxy-pyridin-3-yl)-acetamide (0.70 g, 3.00 mmol), N- methyl-N-phenylcarbamoyl chloride (0.51 g, 3.00 mmol) and 1, 4-diazabicyclo [2.2. 2] octane (0.34 g, 3.00 mmol) in dimethylformamide (15 ml) was stirred at room temperature for 1 hour.

Water was added and the precipitates were collected by suction. The solids were dissolved in dichloromethane and the solution was dried over sodium sulphate, filtered and evaporated in vacuo. The residue was crystallised from ethyl acetate: heptane yielding the title compound (0.79 g, 72% yield) as a brown solid.

'H NMR (300MHz, CDCI3) : 60. 86-1.01 (m, 2H), 1.05-1. 37 (m, 3H), 1.60-1. 78 (m, 5H), 1.83 (m, 1H), 2.13 (d, 2H), 3.46 (br. s, 3H), 6.90 (br. s, 1H), 7.27 (m, 1H), 7.39 (m, 4H), 7.98 (d, 1 H), 8.12 (s + br. s, 2H, CH + NH); HPLC-MS (Method A): m/z = 368 (M+H); Rt = 4.04 min.

Example 267 Methyl-phenyl-carbamic acid 5- (4-methoxy-phenoxy)-pyrimidin-2-yl ester A solution of 5- (4-methoxy-phenoxy)-pyrimidin-2-ol (0.44 g, 2.00 mmol), N methyl-N- phenylcarbamoyl chloride (0.34 g, 2.00 mmol) and 1, 4-diazabicyclo [2.2. 2] octane (0.22 g, 2.00 mmol) in dimethylformamide (15 ml) was stirred at room temperature for 1 hour. Water was added and the precipitates were collected by suction. The solids were dissolved in di- chloromethane and the solution was dried over sodium sulphate, filtered and evaporated in vacuo. The residue was crystallised from ethyl acetate: heptane yielding the title compound (0.55 g, 79% yield) as an off-white solid.

'H NMR (300MHz, CDCI3) : 83. 43 (br. s, 3H), 3. 82 (s, 3H), 6.91 + 7.00 (AB-system, 2 x 2H), 7.26 (m, 1 H), 6.39 (m, 4H), 8.33 (s, 2H); HPLC-MS (Method A): m/z = 352 (M+H); Rt = 4.02 min.

Example 268 Methyl-phenyl-carbamic acid 5-(3s4-dichloro-phenoxy)-pyrimidin-2-yl ester A solution of 5- (3, 4-dichloro-phenoxy)-pyrimidin-2-ol (0.51 g, 2.00 mmol), N-methyl-N-

phenylcarbamoyl chloride (0.34 g, 2.00 mmol) and 1, 4-diazabicyclo [2.2. 2] octane (0.22 g, 2.00 mmol) in dimethylformamide (15 ml) was stirred at room temperature for 1 hour. Water was added and the precipitates were collected by suction. The solids were dissolved in di- chloromethane and the solution was dried over sodium sulphate, filtered and evaporated in vacuo. The residue was crystallised from ethyl acetate: heptane yielding the title compound (0.51 g, 65% yield) as an off-white solid.

'H NMR (300MHz, CDC13) : 3. 44 (br. s, 3H), 6.89 (dd, 1H), 7.14 (d, 1H), 7.27 (m, 1H), 7.39 (m, 4H), 7.44 (d, 1 H), 8.42 (s, 2H); HPLC-MS (Method A): m/z = 390 (M+H); Rt = 4.66 min.

Example 269 Methyl-phenyl-carbamic acid 6-pyridin-2-ylmethyl-pyridazin-3-yl ester A solution of 6- (2-pyridinylmethyl)-3-pyridazinol (100 mg, 0.53 mmol), N-methyl-N- phenylcarbamoyl chloride (91 mg, 0.53 mmol) and 1, 4-diazabicyclo [2.2. 2] octane (60 mg, 0.53 mmol) in dimethylformamide (10 ml) was stirred at room temperature for 2 hours. Water was added and the solution was extracted twice with dichloromethane. The combined or- ganic layers were dried over sodium sulphate, filtered and evaporated in vacuo. The residue was purified by flash column chromatography (SiO2, ethyl acetate) yielding the title com- pound (70 mg, 41 % yield) as a yellow oil.

'H NMR (300MHz, CDCI3) : 83. 42 (br. s, 3H), 4.50 (s, 2H), 7.11-7. 33 (m, 4H), 7.39 (d, 4H), 7.60 (m, 2H), 8.52 (d, 1 H) ; HPLC-MS (Method A): m/z = 321 (M+H); Rt = 1.98 min.

Example 270 Methyl-phenyl-carbamic acid 6- (4-methoxy-benzyl)-pyridazin-3-yl ester A solution of 6- (2-pyridinylmethyl)-3-pyridazinol (97 mg, 0.45 mmol), N-methyl-N- phenylcarbamoyl chloride (76 mg, 0.45 mmol) and 1, 4-diazabicyclo [2.2. 2] octane (50 mg, 0.45 mmol) in dimethylformamide (10 mi) was stirred at room temperature for 2 hours. Water was added and the solution was extracted twice with dichloromethane. The combined or- ganic layers were dried over sodium sulphate, filtered and evaporated in vacuo. The residue was purified by flash column chromatography (Si02, ethyl acetate: heptane (50: 50) ) yielding the title compound (117 mg, 41 % yield) as a white solid.

'H NMR (300MHz, CDC13) : 53. 43 (br. s, 3H), 3.79 (s, 3H), 4.28 (s, 2H), 6. 83 (d, 2H), 7.17 (d, 2H), 7.27 (m, 3H), 7.40 (d, 4H); HPLC-MS (Method A): m/z = 350 (M+H); Rt = 3.60 min.

Example 271 Methyl-phenyl-carbamic acid 6- (2, 4-dichloro-benzyl)-pyridazin-3-yl ester A solution of 6- (2, 4-dichlorobenzyl)-3-pyridazinol (98 mg, 0.38 mmol), N-methyl-N- phenylcarbamoyl chloride (65 mg, 0.38 mmol) and 1, 4-diazabicyclo [2.2. 2] octane (43 mg, 0.38 mmol) in dimethylformamide (10 ml) was stirred at room temperature for 2 hours. Water was added and the solution was extracted twice with dichloromethane. The combined or- ganic layers were dried over sodium sulphate, filtered and evaporated in vacuo. The residue was purified by flash column chromatography (Si02, ethyl acetate: heptane (40: 60) ) yielding the title compound (119 mg, 80% yield) as a yellow oil.

'H NMR (300MHz, CDCI3) : 83. 43 (br. s, 3H), 4.42 (s, 2H), 7.17-7. 44 (m, 10H); HPLC-MS (Method A): m/z = 388 (M+H); Rt = 4.44 min.

Example 272 (General procedure 15) 4-Pyridin-2-yl-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy) phenyl ester The hydrochloride of the title compound was prepared from 4- (5-trifluoromethyl-pyridin-2- yloxy) phenyl chloroformate and 1-pyridin-2-yl-piperazine. White crystals, yield 87 %; m. p.

247-248 °C ; HPLC-MS: m/z = 445 (M+H) ; IR (KBr): v 1713 (C=O) cm~1.

Example 273 (General procedure 15) 4- (1, 3-Benzodioxol-5-yl)-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)- phenyl ester The hydrochloride of the title compound was prepared from 4- (5-trifluoromethyl-pyridin-2- yloxy)-phenyl chloroformate and 1- (1, 3-benzodioxol-5-yl)-piperazine. The crude product was partitioned between dichlorormethane and 1 M aqueous sodium carbonate. The organic layer was washed with water, dried and evaporated. The residue was triturated with ethyl acetate-heptane (1: 4) and the precipitate was collected by filtration and dried to give the title compound. Yield 39 %; m. p. 146-147 °C ; 1H NMR (DMSO-d6) : 88. 60-8.56 (br, 1 H), 8. 29- 8.20 (dd-like, 1 H), 7.31-7. 20 (m, 5H), 6.84-6. 72 (d-like, 1 H), 6.76-6. 72 (d-like, 1 H), 6.45- 6.36 (dd-like, 1H), 3.81-3. 47 (br m, 4H), 3.16-3. 00 (br, m, 4H); HPLC-MS: m/z = 488 (M+H); IR (KBr): v 1719 (C=O) cm~1.

Example 274 (General procedure 15)

4-[2-(2-Hydroxyethoxy) ethyl]-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2- yloxy)-phenyl ester The hydrochloride of the title compound was prepared from 4- (5-trifluoromethyl-pyridin-2- yloxy)-phenyl chloroformate and 2- (2-hydroxyethoxy) ethyl-piperazine. Yield 13 % ;'H NMR (DMSO-d6) : 510. 8 (br), 8.61-8. 54 (br, 1H), 8.30-8. 21 (dd-like, 1H), 7.32-7. 19 (m, 5H), 4. 3 - 3. 9 (br, 2H), 3.9-3. 0 (br m, alicyclics and aliphatics + water); HPLC-MS: m/z = 456 (M+H); IR (KBr): v 1724 (C=O) cm-1.

Example 275 (General procedure 15) 4-(Diphenylmethyl)piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester The hydrochloride of the title compound was prepared from 4- (5-trifluoromethyl-pyridin-2- yloxy)-phenyl chloroformate and 1- (diphenylmethyl) piperazine, white crystals, yield 74 %; m. p. 168-169 °C ; 'H NMR (DMSO-d6): #12. 4 (br, 1H), 8.60-8. 54 (d-like m, 1H), 8.28-8. 20 (dd-like m, 1H), 7.98-7. 82 (br, 2H), 7.55-7. 15 (br m, 13 H), 5.6 (br, 1 H), 4.35-3. 48 (br, 3H), 3.35-3. 0 (br, 5H) ; IR (KBr) : v 1723 (C=O) cm~1.

Example 276 (General procedure 15) 4- (4-tert-Butylbenzyl) piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy) phenyl ester The hydrochloride of the title compound was prepared from 4- (5-trifluoromethyl-pyridin-2- yloxy)-phenyl chloroformate and 1- (4-tert-butylbenzyl) diphenylmethyl) piperazine, white crys- tals, yield 56 %; m. p. 274-275 °C ; HPLC-MS: m/z = 514 (M+H) ; IR (KBr): v 1721 (C=O) crri 1 Example 277 (General procedure 15) 4- (4-Fluorobenzyl)-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester The hydrochloride of the title compound was prepared from 4- (5-trifluoromethyl-pyridin-2- yloxy)-phenyl chloroformate and 1- (4-fluorobenzyl) piperazine, white crystals, yield 69 %;

m. p. 240-243 °C ; HPLC-MS: m/z = 476 (M+H), 498 (M+Na) ; IR (KBr): v 1720 (C=O) cm'.

Example 278 (General procedure15) 4-(2-Thienylethyl) piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy) phenyl es- ter The hydrochloride of the title compound was prepared from 4- (5-trifluoromethyl-pyridin-2- yloxy)-phenyl chloroformate and 1- (2-thienylethyl) piperazine, white crystals, yield 62 %; m. p.

236-237 °C ;'H NMR (DMSO-d6) : 611. 51 (br s, 1H), 8.61-8. 54 (br m, 1H), 7.48-7. 17 (m, 6H), 7.06-6. 89 (m, 2H), 4.4-3. 9 (br, 2H), 3.9-2. 6 (br m, 16.5 H-12H + water); HPLC-MS: m/z = 478 (M+H) ; IR (KBr): v 1714 (C=O) cm~1.

Example 279 (General procedure 15) 4- (1-Phenylethyl) piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy) phenyl es- ter The crude hydrochloride of the title compound was prepared from 4- (5-trifluoromethyl- pyridin-2-yloxy)-phenyl chloroformate and 1- (1-phenylethyl) piperazine. Trituration with water, filtering and drying of the residue gave white crystals, yield 31 %; m. p. 242 °C ;'H NMR (DMSO-d6) : 611. 56 (br s, 1 H), 8.61-8. 52 (br m, 1 H), 8.30-8. 19 (dd-like m, 1 H), 7.77-7. 31 (br m, 5H), 7.31-7. 13 (m, 5H), 4.60-3. 27 (br m, 6H + water), 3.27-2. 57 (br, 3H), 1.73 (br d, 3H); IR (KBr): v 1712 (C=O) cm~1.

Example 280 (General procedure 15) 4-Octylpiperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy) phenyl ester The crude hydrochloride of the title compound was prepared from 4- (5-trifluoromethyl- pyridin-2-yloxy)-phenyl chloroformate and 1-(1-phenylethyl) piperazine. Trituration with water, filtering and drying of the residue gave white crystals, yield 31 %; m. p. 244-245 °C ;'H NMR (DMSO-d6) : 5 11. 16 (br s, 1 H), 8.61-8. 57 (br m, 1 H), 8.30-8. 20 (dd-like m, 1 H), 7.32-7. 18 (m, 5H), 4.39-3. 96 (br, 2H), 3.77-3. 38 (br, 4H), 3.25-2. 88 (br, 4H), 1. 84-1. 58 (br, 2H), 1.42-1. 12 (brs, 10H), 0.87 (br t, 3H); IR (KBr): v 1731,1713 (C=O) cm~1.

Example 281 (General procedure 15) 4- (3-Dimethylamino-propyl)-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-

phenyl ester The crude hydrochloride of the title compound was prepared from 4- (5-trifluoromethyl- pyridin-2-yloxy)-phenyl chloroformate and 1- (3-dimethylaminopropyl) piperazine. A suspen- sion of the product in ether was stirred with an excess of HCI in ether and the precipitate was washed with ether and dried to give the dihydrochloride of the title compound as white crys- tals, m. p. 292-293 °C ; 1H NMR (DMSO-d6) : a 11. 35 (br s, 1 H), 10.46 (br s, 1 H), 8.61-8. 52 (br m, 1 H), 8.31-8. 17 (m, 1 H), 7.35-7. 16 (m, 5H), 4.45-4. 00 (br, 2H), 3.80-3. 45 (br, 4H), 3.30-3. 01 (br, 6H), 2.78 (br s, 6H), 2.31-2. 07 (br, 2H) ; IR (KBr): v 1731,1713 (C=O) cm~1.

Example 282 (General procedure 15) 4-Pyrimidin-2-yl-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester The hydrochloride of the title compound was prepared from 4- (5-trifluoromethyl-pyridin-2- yloxy)-phenyl chloroformate and 1- (pyrimidin-2-yl) piperazine. The crude product was dried in vacuo at 50 °C for 80 min and extracted with ether. The ether phase was evaporated and the residue was purified by flash chromatography on silica eluted with ethyl acetate-heptane 1: 1 to give the title compound as white needles. Yield 14 %; m. p. 120-121 °C ;'H NMR (DMSO- d6) : 5 8. 61-8.56 (br, 1H), 8.41 (d, J = 4.8 Hz, 2H), 8. 29-8. 20 (dd-like, 1H), 7.31-7. 20 (m, 5H), 6,69 (t-like m, J-4. 8 Hz, 1 H), 3.94-3. 78 (br s, 4H), 3.78-3. 45 (br d, 4H); HPLC-MS: m/z = 446 (M+H); IR (KBr): v 1719 (C=O) cm~1.

Example 283 (General procedure 15) 4-Cyclopropylmethyl-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester The hydrochloride of the title compound was prepared from 4- (5-trifluoromethyl-pyridin-2- yloxy)-phenyl chloroformate and 1-cyclopropylpiperazine, yield 62 %. Recrystallisation from 0.2 M HCI gave white crystals, m. p. 238-239 °C ; 1H NMR (DMSO-d6) : a 11. 51 (br s, 1 H), 8. 61-8. 55 (m, 1 H), 8.30-8. 20 (m, dd, 1 H), 7.32-7. 19 (m, d+s, 5H), 4.44-4. 00 (br, 2H), 3.80-3. 40 (br m, 4H), 3.29-2. 93 (br m, 4H), 1.28-1. 05 (br m, 1 H), 0.75-0. 58 (m, 2H), 0.50-0. 35 (m, 2H). IR (KBr) : v 1730,1713 (C=O) cm~1.

Example 284 (General procedure 15) 4-Methyl-1, 4-diazepane-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy) phenyl ester

The hydrochloride of the title compound was prepared from 4- (5-trifluoromethyl-pyridin-2- yloxy)-phenyl chloroformate and 1-methylhomopiperazine ; white crystals, m. p. 210-211 °C ;'H NMR (DMSO-d6) : 3 11. 27 (br s, 1 H), 8.61-8. 54 (m, 1 H), 8.30-8. 20 (dd-like m, 1 H), 7.34-7. 18 (m, 5H), 4.13-3. 08 (br, 11 H, 8H + water), 2.80 (br s, 3H), 2.47-1. 98 (br m, 2H); IR (KBr): v 1723,1711 (C=O) cm~1.

Example 285 (General procedure 15) 4-Phenethyl-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester The hydrochloride of the title compound was prepared from 4- (5-trifluoromethyl-pyridin-2- yloxy)-phenyl chloroformate and 1-phenethylpiperazine, yield 54 %. Recrystallisation from 99% EtOH gave white crystals, m. p. 245-247 °C ;'H NMR (DMSO-d6) : a 11.72 (br, 1 H), 8.63-8. 53 (br, 1 H), 8.31-8. 19 (dd-like m, 1 H), 7.44-7. 16 (m, 10H), 4.44-4. 01 (br, 2H), 3.83-3. 45 (br, 4H), 3.45-2. 95 (br,-8H, 6H + water) ; IR (KBr): v 1713 (C=O) cm~1.

Example 286 (General procedure 15) 4-Pyridin-2-ylmethyl-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester The hydrochloride of the title compound was prepared from 4- (5-trifluoromethyl-pyridin-2- yloxy)-phenyl chloroformate and 1-pyridin-2-ylmethyl-piperazine. White crystals, yield 64 %; m. p. 189-190 °C ;'H NMR (DMSO-d6) : 45 8. 72-8.63 (m, 1H), 8.60-8. 55 (br, 1H), 8.29- 8. 20 (dd-like, 1 H), 8.02-7. 90 (m, 1 H), 7. 80-7. 65 (m, 1 H), 7.56-7. 45 (m, 1 H), 7.31-7. 22 (m, 5H), 4.52 (br s, 2H), 4.06-3. 68 (br s, 4H), 3.68-2. 93 (br, 4H + NH + water); HPLC-MS: m/z = 459 (M+H) ; IR (KBr): v 1717 (C=O) cm~1.

Example 287 (General procedure 15) 4-Pyridin-3-ylmethyl-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester The hydrochloride of the title compound was prepared from 4- (5-trifluoromethyl-pyridin-2- yloxy)-phenyl chloroformate and 1-pyridin-3-ylmethyl-piperazine. Trituration with water, filter- ing and drying of the residue gave white crystals.'H NMR (DMSO-d6) : 68. 78-8.51 (m, 3H), 8.30-8. 18 (dd-like, 1 H), 8. 12-8.00 (br d, 1 H), 7.57-7. 46 (m, 1 H), 7.32-7. 17 (m, 5H), 4.65

- 4. 11 (br, 2H), 4.11-2. 78 (br m, 6H + water); HPLC-MS: m/z = 459 (M+H) ; IR (KBr) : v 1723 (C=O) cm~1.

Example 288 (General procedure 15) 4- (3-Phenylpropyl) piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester The hydrochloride of the title compound was prepared from 4- (5-trifluoromethyl-pyridin-2- yloxy)-phenyl chloroformate and 1- (3-phenylpropyl) piperazine, yield 68 %. m. p. 235-238 °C ; 1H NMR (DMSO-d6) : 11.51 (br, 1 H), 8.61-8. 55 (br, 1 H), 8. 29-8. 20 (dd-like m, 1 H), 7.38-7. 16 (m, 10H), 4.38-3. 96 (br, 2H), 3.83-3. 40 (br, 4H), 3.30-2. 91 (br, 4H), 2.75-2. 57 (t-like m, 2H), 2.20-1. 94 (m, 2H); IR (KBr): v 1715 (C=O) cm'.

Example 289 (General procedure 15) 4- (4-Phenylbutyl) piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl es- ter The hydrochloride of the title compound was prepared from 4- (5-trifluoromethyl-pyridin-2- yloxy)-phenyl chloroformate and 1- (4-phenylbutyl) piperazine, yield 71 %. m. p. 232-234 °C ; 'H NMR (DMSO-d6) : 5 11.32 (br s, 1 H), 8. 61-8. 55 (br, 1 H), 8. 29- 8. 20 (dd-like m, 1 H), 7.36 - 7. 13 (m, 10H), 4.40-3-97 (br, 2H), 3.81-3. 39 (br m, 4H), 3.26-2. 91 (br, 4H), 2.71-2. 55 (t-like m, 2H), 1.88-1. 51 (br m, 4H); IR (KBr) : v 1728,1713 (C=O) cm~1.

Example 290 (General procedure 15) 4-Benzyl-1, 4-diazepane-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester The hydrochloride of the title compound was prepared from 4- (5-trifluoromethyl-pyridin-2- yloxy)-phenyl chloroformate and 1-benzylhomopiperazine, crude yield 70 %. 0.20 g Of the crude product was heated with 3 ml of water, cooled at 0 °C, the precipitate filtered off and dried; m. p. 231-233 °C; 1H NMR (DMSO-d6): #11. 38 (br s, 1 H), 8.62-8. 55 (br, 1 H), 8.30- 8.20 (dd-like m, 1H), 7.76-7. 60 (br, 2H), 7. 52- 7. 41 (br m, 3H), 7.32-7. 19 (m, 5H), 4.38 (br s, 2H), 4.18-3. 01 (br m, 8H + water), 2.6-2. 0 (br, 2H + DMSO); IR (KBr): v 1726,1710 (C=O) cm~1.

Example 291 (General procedure 15) 4- (3, 4-Dichlorophenyl) piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy) phenyl ester The hydrochloride of the title compound was prepared from 4- (5-trifluoromethyl-pyridin-2- yloxy)-phenyl chloroformate and 1- (3, 4-dichlorophenyl) piperazine. The crude product was partitioned between dichlorormethane and 2 M aqueous sodium carbonate. The organic layer was washed with water, dried and evaporated. The residue was triturated with ethyl acetate-heptane (1: 4) and the precipitate was collected by filtration and dried to give the title compound as white crystals. Yield 28 % ; m. p. 115-116 °C ;'H NMR (DMSO-d6) : # 8.61- 8.55 (br, 1H), 8.30-8. 20 (dd-like, 1H), 7.48-7. 40 (d-like, 1 H), 7.31-7. 16 (m, 6H), 7.04-6. 94 (dd-like, 1 H), 3.83-3. 47 (br m, 4H), 3.36-3. 24 (br s, 4H + water); HPLC-MS: m/z = 512 (M+H); IR (KBr): v 1724,1706 cm'.

Example 292 (General procedure 15) 4- (4-Fluorophenyl) piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy) phenyl ester The hydrochloride of the title compound was prepared from 4- (5-trifluoromethyl-pyridin-2- yloxy)-phenyl chloroformate and 1- (4-fluorophenyl) piperazine. White crystals, yield 20 %; m. p. 131-132 °C ; 1H NMR (DMSO-d6) : # 8.61-8. 53 (br, 1H), 8.30-8. 19 (dd-like, 1H), 7.33- 7.17 (m, 5H), 7.17-6. 95 (m, 4H), 3.85-3. 47 (brd, 4H), 3.25-3. 07 (br m, 4H); HPLC-MS: m/z = 462 (M+H) ; IR (KBr): v 1739,1714 cm~1.

Example 293 (General procedure 15) 4-(2-Chlorophenyl)piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy) phenyl ester The the hydrochloride of title compound was prepared from 4- (5-trifluoromethyl-pyridin-2- yloxy)-phenyl chloroformate and 1- (2-chlorophenyl) piperazine. Drying in vacuo at 50 °C for 3½ h gave the title compound ; 1H NMR (DMSO-d6) : 5 8. 61-8.55 (br, 1 H), 8.29-8. 20 (dd- like, 1H), 7.53-7. 41 (m, 1H), 7.39-7. 17 (m, 7H), 7.14-7. 03 (m, 1H), 4.58 (br s, NH + wa- ter), 3.85-3. 55 (br m, 4H), 3.12-2. 99 (br m, 4H); HPLC-MS: m/z = 478 (M+H) ; IR (KBr): v 1733 (C=O) cm'.

Example 294 (General procedure 15) (2-Dimethylamino-ethyl) methylcarbamic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl es- ter The hydrochloride of the title compound was prepared from 4- (5-trifluoromethyl-pyridin-2- yloxy)-phenyl chloroformate and N, N, N'-trimethylethylenediamine ; m. p. 139-140 °C ;'H NMR (MeOH-d6) : 6 8.45-8. 38 (br, 1H), 8.15-8. 05 (dd-like m, 1H), 7.31-7. 11 (m, 5H), 3.84 - 3. 73 (br m, 2H), 3.54-3. 38 (br m, 3H), 3.19 (br s, 2H), 2.99 (br s, 6H); traces of impurities at 3.9 (br) and 3.1 (br) ; IR (KBr): v 2695,1705 cm' (C=0) cm'\ Example 295 (General procedure 15) 4-Methylpiperazine-1-carboxylic acid 4-chlorophenyl ester The hydrochloride of the title compound was prepared from 4-chlorophenyl chloroformate and 1-methylpiperazine, yield 81 %. White crystals, m. p. 237-240 °C ;'H NMR (DMSO-d6) : , 5 11. 67 (br s, 1 H), 7.50, 7.45, 7.24, 7.20 (AB-system, d = 7.47 and 7.22 ; J = 8.84 Hz, 4H), 4.40-3. 91 (br, 2H, 3.77-2. 92 (br m, 6H + water), 2.77 (s, 3H); IR (KBr): v 1717 (C=O) cm~1.

Example 296 (General procedure 15) 4- (4-Phenylbutyl) piperazine-1-carboxylic acid 4-chlorophenyl ester The hydrochloride of the title compound was prepared from 4-chlorophenyl chloroformate and 1- (4-phenylbutyl) piperazine, yield 86 %. White crystals, m. p. 230-232 °C ;'H NMR (DMSO-d6) : a 11.43 (br, 1 H), 7.51-7. 43 (d-like m, 2H), 7.33-7. 15 (m, 7H), 4.33-3. 95 (br, max at 4.21 and 4.10 ppm; 2H), 3.72-3. 36 (br m, 4H), 3.22-2. 96 (br, max at 3.10 ppm, 4H), 2.62 (t, J= 7.54 Hz, 2H), 1.84-1. 69 (m, 2H), 1.69-1. 54 (m, 2H) ppm; IR (KBr): v 1736,1720 (C=O) cm~1.

Example 297 (General procedure 15) 4-[2-(2-Hydroxyethoxy) ethyl] piperazine-1-carboxylic acid 4- (4-trifluoromethylphenoxy) phenyl ester The hydrochloride of the title compound was prepared from 4- (4- trifluoromethylphenoxy) phenyl chloroformate and 2- (2-hydroxyethoxy) ethyl-piperazine. Pale powder, m. p. 176-178 °C ; 1H NMR (MeOH-d4) : 5 Two AB-systems: 7.68-7. 58 (d-like, 2H)

and 7.29-7. 04 (m, 6H); 4.74-3. 18 (complex, 16 H, partly overlapping with MeOH-d4) ; HPLC-MS m/z = 455 (M+H), 477 (M+Na), Rt= 3.08 min. ; IR (KBr): v 1718 (C=O) cm'.

Example 298 (General procedure 15) 4- (1-Ethylpropyl) piperazine-1-carboxylic acid 4- (4-trifluoromethylphenoxy) phenyl ester The hydrochloride of the title compound was prepared from 4- (4- trifluoromethylphenoxy) phenyl chloroformate and 1-(1-ethylpropyl) piperazine, yield 74 %. r White crystals, 1H NMR (DMSO-d6) : a 10. 59 (br s, 1 H), 2 AB-systems : 7.81-7. 70 (d-like, 2H) and 7.31-7. 09 (m, 6H); 4.38-3. 99 (br s, 2H), 3.90-3. 38 (br, 4H), 3. 33- 2. 99 (br, 3H), 2.01-1. 77 (m, 2H), 1.77-1. 49 (m, 2H), 0.98 (t, 6H); HPLC-MS m/z = 437 (M+H).

Example 299 (General procedure 15) 4-Cycloheptylpiperazine-1-carboxylic acid 4- (4-trifluoromethyl-phenoxy) phenyl ester The hydrochloride of the title compound was prepared from 4- (4- trifluoromethylphenoxy) phenyl chloroformate and 1-cycloheptylpiperazine. The crude product was partitioned between dichlorormethane and aqueous sodium carbonate. The organic layer was washed with water, dried and evaporated. The residue was triturated with ethyl acetate-heptane (1: 4) and the precipitate was collected by filtration and dried to give the title compound. White crystals,'H NMR (MeOH-d4) : 6 Two AB-systems: 7.68-7. 58 (d-like, 2H) and 7.23-7. 04 (m, 6H); 3.86-3. 50 (br d, 4H), 2.98-2. 66 (br, 5H), 2.04-1. 37 (m, 12H); HPLC-MS m/z = 463 (M+H) ; IR (KBr): v 1730, 1707 cm~1.

Example 300 (General procedure 15) 4-Cyclohexylpiperazine-1-carboxylic acid 4- (4-trifluoromethyl-phenoxy) phenyl ester The hydrochloride of the title compound was prepared from 4- (4- trifluoromethylphenoxy) phenyl chloroformate and 1-cyclohexylpiperazine, yield 80 %. White crystals, m. p. 290-291 °C,'H NMR (DMSO-d6) : F 10. 82 (br s, 1 H), 2 AB-systems: 7.83- 7.69 (d-like, 2H) and 7.32-7. 10 (m, 6H); 4.40-4. 02 (br, 2H), 3.75-3. 39 (br, 4H), 3. 31- 2. 98 (br, 3H), 2.23-2. 02 (m, 2H), 1.92-1. 74 (m, 2H), 1.70-0. 97 (m, 6H); HPLC-MS m/z = 449 (M+H) ; IR (KBr): v 1717 (C=O) cm~1.

Example 301 (General procedure 15)

4- (4-Chlorobenzyl) piperazine-1-carboxylic acid 4- (4-trifluoromethylphenoxy) phenyl ester The hydrochloride of the title compound was prepared from 4- (4- trifluoromethylphenoxy) phenyl chloroformate and 1- (4-chlorobenzyl) piperazine, yield 86 %.

White crystals, m. p. 232-234 °C ; 1H NMR (DMSO-d6) : my 11.92 (br s, 1 H), 3 AB-systems: 7.83-7. 62 (t-like, 4H) and 7.62-7. 48 (d-like, 2H), and 7.32-7. 07 (m, 6H); 4.51-3. 95 (br s at 4.37 ppm overlapping with br signal at 4.2 ppm, 4H), 3.95-2. 95 (br m, 9H: 6H + water) ; IR (KBr): v 1717 (C=O) cm'.

Example 302 (General procedure 15) 4- (4-Methylbenzyl) piperazine-1-carboxylic acid 4- (4-trifluoromethylphenoxy) phenyl ester The hydrochloride of the title compound was prepared from 4- (4- trifluoromethylphenoxy) phenyl chloroformate and 1- (4-methylbenzyl) piperazine, yield 96 %.

White crystals, m. p. 250-252°C ; HPLC-MS m/z = 472 (M+H) ; IR (KBr): v 1720 (C=O) cm~1.

Example 303 (General procedure 15) 4- (4-Methoxybenzyl) piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester The hydrochloride of the title compound was prepared from 4- (5-trifluoromethyl-pyridin-2- yloxy)-phenyl chloroformate and 1- (4-methoxybenzyl) piperazine, yield 78 %. White crystals, m. p. 237-238 °C ; HPLC-MS m/z = 488 (M+H) ; IR (KBr) : v 1719 (C=O) cm~1.

Example 304 (General procedure 15) <BR> <BR> <BR> <BR> 4- (2-Chloro-6-fluoro-benzyl)-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)- phenyl ester The hydrochloride of the title compound was prepared from 4- (5-trifluoromethyl-pyridin-2- yloxy)-phenyl chloroformate and 1- (2-chloro-6-fluorobenzyl) piperazine. White crystals, m. p.

204-205 °C (from ethanol) ; HPLC-MS m/z = 510 (M+H) ; IR (KBr): v 1726 (C=O) cm' ; Example 305 (General procedure 15) 4- (3-Methoxyphenyl) piperazine-1-carboxylic acid 4- (4-trifluoromethylphenoxy) phenyl ester

The hydrochloride of the title compound was prepared from 4- (4- trifluoromethylphenoxy) phenyl chloroformate and 1- (3-methoxyphenyl) piperazine. White crystals, m. p. 168-171 °C (sinters at 160 °C) ; HPLC-MS m/z = 473 (M+1) ; IR (KBr): v 1739, 1716 (C=O) cm~1.

Example 306 (General procedure 15) 4-Benzyl-piperazine-1-carboxylic acid 4- (3-chloro-5-trifluoromethyl-pyridin-2-yloxy) phenyl es- ter The hydrochloride of the title compound was prepared from 4- (3-chloro-5-trifluoromethyl- pyridin-2-yloxy)-phenyl chloroformate and 1-benzyl-piperazine, yield 94 %. White crystals ; m. p. 111-113 °C (resolidifies) and 114-115 °C ; HPLC-MS m/z = 492 (M+H).

Example 307 (General procedure 8) Methyl-phenyl-carbamic acid 4-iodo-pyrazol-1-yl ester The title compound was prepared from 1-hydroxy-4-iodopyrazole and N-methyl-N- phenylcarbamoyl chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (98%, oil).

'H NMR (300MHz ; CDCI3) : my 3.44 (bs, 3H), 7.30-7. 48 (m, 7H).; HPLC-MS: m/z = 343.9 (M+1); Rt = 4. 12 min.

Example 308 (General procedure 8) Methyl-phenyl-carbamic acid benzotriazol-1-yl ester The title compound was prepared from 1-hydroxybenzotriazole and N-methyl-N- phenylcarbamoyl chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (98%, crystallizes slowly).

'H NMR (300MHz ; CDCI3) : my 3.50 (bs, 3H), 7.37-7. 57 (m, 8H), 8. 04 (d, 1 H). ; HPLC-MS: m/z = 269.0 (M+1); Rt = 3.69 min.

Example 309 (General procedure 8) Methyl-phenyl-carbamic acid [1,2, 3] triazolo [4,5- b] pyridin-3-yl ester The title compound was prepared from [1,2, 3] Triazolo [4, 5-b] pyridin-3-ol and N-methyl-N- phenylcarbamoyl chloride applying the general procedure 8. The crude product was purified

by flash chromatography (Quad flash 12, EtOAc-heptane) (99%, oil).

'H NMR (300MHz ; CDCI3) : 6 3.50 (bs, 3H), 7.30-7. 60 (m, 6H), 8.40 (d, 1H), 8.75 (d, 1H) ; HPLC-MS: m/z= 270.0 (M+1); Rt = 3.18 min.

Example 310 (General procedure 8) Methyl-phenyl-carbamic acid 3- (2-nitro-phenyl)-pyrazol- 1-yl ester The title compound was prepared from 1-hydroxy-3- (2-nitrophenyl) pyrazole and N-methyl-N- phenylcarbamoyl chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (94%, oil).

'H NMR (300MHz ; CDCI3) : 5 3. 45 (bs, 3H), 6.44 (bs, 1H), 7.30-7. 50 (m, 7H), 7.58 (dt, 1H), 7.72-7. 78 (m, 2H); HPLC-MS: m/z = 339, 1 (M+1) ; Rt = 4.15 min.

Example 311 (General procedure 8) Methyl-phenyl-carbamic acid 3- (4-nitro-phenyl)-pyrazol- 1-yl ester The title compound was prepared from 1-hydroxy-3- (4-nitrophenyl) pyrazole and N-methyl-N- phenylcarbamoyl chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (99%, yellow crystals).

'H NMR (300MHz ; CDCI3) : zu 3.47 (bs, 3H), 6.70 (bd, 1H), 7.32-7. 50 (m, 6H), 7.94 (d, 2H), 8.26 (d, 2H); HPLC-MS: m/z= 339.1 (M+1) ; Rt = 4.41 min.

Example 312 (General procedure 8) Methyl-phenyl-carbamic acid 3-pyridin-2-yl-pyrazol-1-yl ester The title compound was prepared from 1-hydroxy-3- (2-pyridyl) pyrazole and N-methyl-N- phenylcarbamoyl chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (90%, oil).

'H NMR (300MHz ; CDCI3) : a 3.48 (bs, 3H), 6.95 (d, 1H), 7.20 (dd, 1H), 7.30-7. 48 (m, 6H), 7.70 (dt, 1 H), 7.93 (d, 1 H), 8.61 (d, 1 H) ; HPLC-MS: m/z = 295.1 (M+1) ; Rt = 2.75 min.

Example 313 (General procedure 8) Methyl-phenyl-carbamic acid 3-thiophen-2-yl-pyrazol-1- yl ester The title compound was prepared from 1-hydroxy-3- (2-thienyl) pyrazole and N-methyl-N-

phenylcarbamoyl chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (66%, oil).

'H NMR (300MHz ; CDC13) : 5 3.46 (bs, 3H), 6. 48 (bd, 1H), 7.03 (dd, 1H), 7.25 (dd, 1H), 7.30- 7. 48 (m, 7H); HPLC-MS : m/z= 300.1 (M+1) ; Rt = 4.16 min.

Example 314 (General procedure 8) Methyl-phenyl-carbamic acid 3- (2-fluoro-phenyl)- pyrazol-1-yl ester The title compound was prepared from 1-hydroxy-3- (2-fluorophenyl) pyrazole and N-methyl- N-phenylcarbamoyl chloride applying the general procedure 8. The crude product was puri- fied by flash chromatography (Quad flash 12, EtOAc-heptane) (97%, oil).

H NMR (300MHz ; CDCI3) : a 3.48 (bs, 3H), 6.75 (bt, 1H), 7.07-7. 47 (m, 9H), 7.97 (dt, 1H) ; HPLC-MS: m/z = 312.1 (M+1) ; Rt = 4.45 min.

Example 315 (General procedure 8) Methyl-phenyl-carbamic acid 3-bromo-pyrazol-1-yl ester The title compound was prepared from 1-hydroxy-3-bromopyrazole and N-methyl-N- phenylcarbamoyl chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (63%, oil).

'H NMR (300MHz ; CDCI3) : my 3.43 (bs, 3H), 6.31 (d, 1H), 7.26-7. 48 (m, 6H).; HPLC-MS: m/z = 298.0 (M+1); Rt = 3.97 min.

Example 316 (General procedure 8) Methyl-phenyl-carbamic acid 5-iodo-pyrazol-1-yl ester The title compound was prepared from 1-hydroxy-5-iodopyrazole and N-methyl-N- phenylcarbamoyl chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (64%, oil).

'H NMR (300MHz ; CDCI3) : my 3. 48 (bs, 3H), 6.42 (d, 1H), 7.28-7. 47 (m, 6H).; HPLC-MS: m/z = 343.9 (M+1); Rt = 3.81 min.

Example 317 (General procedure 8) Methyl-phenyl-carbamic acid 2-chloro-imidazol-1-yl es- ter The title compound was prepared from 1-hydroxy-2-chloroimidazole, hydrochloride and N- methyl-N-phenylcarbamoyl chloride applying the general procedure 8. The crude product

was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (77%, oil).

'H NMR (300MHz ; CDCI3) : 8 3.45 (bs, 3H), 6.90 (bs, 1H), 7.07 (bs, 1H), 7.35-7. 40 (m, 3H), 7.46 (bt, 2H); HPLC-MS : m/z = 251.9 (M+1); Rt = 3.29 min.

Example 318 (General procedure 8) Methyl-phenyl-carbamic acid 4- (4-methoxy-phenyl)- pyrazol-1-yl ester The title compound was prepared from 1-hydroxy-4- (4-methoxyphenyl) pyrazole and N- methyl-N-phenylcarbamoyl chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (6%, oil).

'H NMR (300MHz ; CDCI3) : a 3.45 (bs, 3H), 3.82 (s, 3H), 6.90 (d, 2H), 7.30-7. 48 (m, 7H), 7.54 (bs, 2H); HPLC-MS: m/z = 346.1 (M+23); Ri = 4.16 min.

Example 319 (General procedure 8) Methyl-phenyl-carbamic acid 5-benzoyl-pyrazol-1-yl es- ter The title compound was prepared from 1-hydroxy-5-benzoylpyrazole and N-methyl-N- phenylcarbamoyl chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (30%, crystals).

'H NMR (300MHz ; CDCI3) : a 3.48 (bs, 3H), 6.69 (bs, 1H), 7.27-7. 52 (m, 8H), 7.63 (t, 1H), 7.79 (d, 2H); HPLC-MS: m/z = 344.0 (M+23); Rt = 4.41 min.

Example 320 (General procedure 8) Methyl-phenyl-carbamic acid 5- (4-methoxy-phenyl)- pyrazol-1-yl ester The title compound was prepared from 1-hydroxy-5- (4-methoxyphenyl) pyrazole and N- methyl-N-phenylcarbamoyl chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (38%, yellow crys- tals).

'H NMR (300MHz ; CDC13) : a 3.33 (bs, 3H), 3. 86 (s, 3H), 6.34 (d, 1H), 6.95 (d, 2H), 7.25-7. 45 (m, 8H); HPLC-MS: m/z = 324.1 (M+1) ; Rt = 4.27 min.

Example 321 (General procedure 8) Methyl-phenyl-carbamic acid 5- (4-dimethylamino- phenyl)-pyrazol-1-yl ester

The title compound was prepared from 1-hydroxy-5- (4-dimethylaminophenyl)-pyrazole and N-methyl-N-phenylcarbamoyl chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (27%, crystals). oh NMR (300MHz ; CDCI3) : a 3.02 (s, 6H), 3.35 (bs, 3H), 6.30 (d, 1H), 6.72 (d, 2H), 7.30-7. 46 (m, 8H); HPLC-MS: m/z = 337. 1 (M+1); Rt = 4. 11 min.

Example 322 (General procedure 8) Methyl-phenyl-carbamic acid 4, 5-diiodo-pyrazol-1-yl es- ter The title compound was prepared from 1-hydroxy-4, 5-diiodopyrazole and N-methyl-N- phenylcarbamoyl chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (76%, crystals).

'H NMR (300MHz ; CDCI3) : 8 3. 45 (bs, 3H), 7.30-7. 50 (m, 6H).; HPLC-MS: mlz = 369.9 (M+1); Rt = 4.56 min.

Example 323 (General procedure 8) Methyl-phenyl-carbamic acid 5-thiophen-2-yl-pyrazol-1- yl ester The title compound was prepared from 1-hydroxy-5- (2-thienyl) pyrazole and N-methyl-N- phenylcarbamoyl chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (51%, crystals).

1H NMR (300MHz ; CDCI3) : a 3.44 (bs, 3H), 6.45 (bs, 1H), 7.09 (dd, 1H), 7.26 (bs, 1H), 7.28- 7.49 (m, 7H); HPLC-MS : m/z = 300.1 (M+1); Rt = 4.18 min.

Example 324 (General procedure 8) Methyl-phenyl-carbamic acid 2- (4-methoxy-phenyl)- imidazol-1-yl ester The title compound was prepared from 1-hydroxy-2- (4-methoxyphenyl) imidazole, hydrochlo- ride and N-methyl-N-phenylcarbamoyl chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (89%, crys- tals). oh NMR (300MHz ; CDC13) : a 3.33 (bs, 3H), 3.86 (s, 3H), 6.92 (d, 2H), 7.04 (d, 1H), 7.10 (bs, 1H), 7.28 (d, 2H), 7.34-7. 50 (m, 3H), 7.60 (bd, 2H); HPLC-MS: m/z= 324.1 (M+1); Rt = 2.87 min.

Example 325 (General procedure 8) Methyl-phenyl-carbamic acid 2-methylsulfanyl-imidazol- 1-yl ester The title compound was prepared from 1-hydroxy-2-methylsulfanyl-imidazole hydrochloride and N-methyl-N-phenylcarbamoyl chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (97%, oil).

'H NMR (300MHz ; CDCI3) : a 2.56 (s, 3H), 3.44 (bs, 3H), 7.00 (bs, 1 H), 7.08 (bs, 1 H), 7.32- 7.49 (m, 5H); HPLC-MS: m/z = 264.1 (M+1); Rt = 2.99 min.

Example 326 (General procedure 8) Methyl-phenyl-carbamic acid 3, 5-bis- (4-methoxy- phenyl)-pyrazol-1-yl ester The title compound was prepared from 1-hydroxy-3, 5-bis- (4-methoxyphenyl) pyrazole and N- methyl-N-phenylcarbamoyl chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (29%, beige crystals).

'H NMR (300MHz ; CDCI3) : a 3.35 (bs, 3H), 3.84 (s, 3H), 3.88 (s, 3H), 6.57 (s, 1H), 6.92 (d, 2H), 6.97 (d, 2H), 7.25-7. 48 (m, 7H), 7.74 (d, 2H); HPLC-MS : m/z = 881. 2 (2M+23); Rt = 5.26 min.

Example 327 (General procedure 8) Methyl-phenyl-carbamic acid 4- (4-fluoro-phenyl)-5- (4- methoxy-phenyl)-3- (4-methylphenyl)-pyrazol-1-yl ester The title compound was prepared from 1-hydroxy-4- (4-fluorophenyl)-5- (4-methoxyphenyl)-3- (4-methylphenyl) pyrazole and N-methyl-N-phenylcarbamoyl chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (11 %, crystals).

'H NMR (300MHz ; CD13) : a 2.32 (s, 3H), 3.32 (bs, 3H), 3.83 (s, 3H), 6.87 (d, 2H), 6.93 (d, 2H), 7.12-7. 48 (m, 13H); HPLC-MS : m/z= 530.2 (M+23); Rt = 6.04 min.

Example 328 (General procedure 8) Methyl-phenyl-carbamic acid 4-benzyl-5- (4-methoxy- phenyl)-3- (methylphenyl)-pyrazol-1-yl ester The title compound was prepared from 1-hydroxy-4-benzyl-5- (4-methoxyphenyl)-3- (4- methylphenyl) pyrazole and N-methyl-N-phenylcarbamoyl chloride applying the general pro- cedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-

heptane) (14%, oil).

'H NMR (300MHz ; CDCI3) : 8 2.31 (s, 3H), 3.31 (bs, 3H), 3.83 (s, 3H), 3.95 (s, 2H), 6.89 (d, 2H), 7.08-7. 39 (m, 13H), 7.43 (d, 2H); HPLC-MS: m/z = 504.2 (M+1); Rt = 6.11 min.

Example 329 (General procedure 8) Methyl-phenyl-carbamic acid 4-acetyl-pyrazol-1-yl ester The title compound was prepared from 1-hydroxy-4-acetylpyrazole and N-methyl-N- phenylcarbamoyl chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (89%, oil).

'H NMR (300MHz ; CDCI3) : my 2.44 (s, 3H), 3.44 (bs, 3H), 7.32-7. 48 (m, 5H), 7.78 (bs, 1H), 7.85 (bs, 1 H).

Example 330 (General procedure 8) Methyl-phenyl-carbamic acid 2- (4-nitro-phenyl)-imidazol- 1-yl ester The title compound was prepared from 1-hydroxy-2- (4-nitrophenyl) imidazole, hydrochloride and N-methyl-N-phenylcarbamoyl chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (90%, yellow crystals).

'H NMR (300MHz ; CDCI3) : a 3.38 (bs, 3H), 7.16 (s, 1H), 7.20 (s, 1H), 7.31 (d, 2H), 7.38-7. 61 (m, 3H), 7.86 (bs, 2H), 8.25 (d, 2H).

Example 331 (General procedure 8) Methyl-phenyl-carbamic acid 2-chloro-5- (4- methylphenyl)-imidazol-1-yl ester The title compound was prepared from 1-hydroxy-2-chloro-5- (4-methylphenyl) imidazole, hy- drochloride and N-methyl-N-phenylcarbamoyl chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (80%, oil).

'H NMR (300MHz ; CDCI3) : a 2.40 (s, 3H), 3.33 (bs, 3H), 7.00 (s, 1H), 7.19-7. 29 (m, 6H), 7.35-7. 50 (m, 3H).

Example 332 (General procedure 8) Methyl-phenyl-carbamic acid 4-formyl-pyrazol-1-yl ester The title compound was prepared from 1-hydroxy-4-formylpyrazole and N-methyl-N-

phenylcarbamoyl chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (73%, oil).

H NMR (300MHz ; CDCI3) : a 3.45 (bs, 3H), 7.29-7. 50 (m, 5H), 7.84 (bs, 1H), 7.90 (bs, 1H), 9.83 (s, 1 H).

Example 333 (General procedure 8) Methyl-phenyl-carbamic acid 4-hydroxymethyl-pyrazol- 1-yl ester The title compound was prepared from 1-hydroxy-4-hydroxymethylpyrazole and N-methyl-N- phenylcarbamoyl chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (62%, oil). oh NMR (300MHz ; CDCI3) : a 2.33 (bs, 1H), 3.40 (bs, 3H), 4.50 (s, 2H), 7.28-7. 46 (m, 7H).

Example 334 (General procedure 8) Methyl-phenyl-carbamic acid 4-phenylethynyl-pyrazol-1- yl ester The title compound was prepared from 1-hydroxy-4-phenylethynylpyrazole and N-methyl-N- phenylcarbamoyl chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (40%, yellow crystals).

'H NMR (300MHz ; CDCI3) : a 3.42 (bs, 3H), 7.30-7. 58 (m, 12H).

Example 335 (General procedure 8) Methyl-phenyl-carbamic acid 2-bromo-imidazol-1-yl es- ter The title compound was prepared from 1-hydroxy-2-bromoimidazole, hydrochloride and N- methyl-N-phenylcarbamoyl chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (63%, oil).

'H NMR (300MHz ; CDCI3) : 6 3.45 (bs, 3H), 6.98 (bd, 1H), 7.11 (bs, 1H), 7.33-7. 50 (m, 5H); HPLC-MS: m/z = 296.0 (M+1) ; Rt = 2.90 min.

Example 336 (General procedure 8) Methyl-phenyl-carbamic acid 2-phenylsulfanyl-imidazol- 1-yl ester The title compound was prepared from 1-hydroxy-2-phenylsulfanylimidazole hydrochloride and N-methyl-N-phenylcarbamoyl chloride applying the general procedure 8. The crude

product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (61%, oil).

'H NMR (300MHz ; CDCI3) : a 3.35 (s, 3H), 7.12 (bd, 1H), 7.17-7. 39 (m, 11H) ; HPLC-MS : m/z = 326.0 (M+1); Rt = 3.65 min.

Example 337 (General procedure 8) Morpholine-4-carboxylic acid imidazol-1-yl ester The title compound was prepared from 1-hydroxyimidazole and 4-morpholine carbonyl chlo- ride applying the general procedure 8. The crude product was purified by preparative HPLC (water-acetonitrile-0. 1% TFA) (36%, crystals).

'H NMR (300MHz ; CDCI3) : my 3.57 (bs, 2H), 3.66 (bs, 2H), 3.78 (t, 4H), 7.12 (bs, 1H), 7.15 (bt, 1 H), 7.90 (s, 1 H) ; HPLC-MS: m/z = 198.1 (M+1); Rt = 0.36 min.

Example 338 (General procedure 8) Morpholine-4-carboxylic acid 2-bromo-imidazol-1-yl es- ter The title compound was prepared from 1-hydroxy-2-bromoimidazole, hydrochloride and 4- morpholine carbonyl chloride applying the general procedure 8. The crude product was puri- fied by flash chromatography (Quad flash 12, EtOAc) (98%, crystals).

'H NMR (300MHz ; CDCI3) : a 3.60 (bs, 2H), 3.71 (bs, 2H), 3.80 (t, 4H), 7.02 (d, 1H), 7.18 (d, 1 H) ; HPLC-MS: m/z = 276.0 (M+1); Rt = 1.73 min.

Example 339 (General procedure 8) Morpholine-4-carboxylic acid 2-chloro-imidazol-1-yl es- ter The title compound was prepared from 1-hydroxy-2-chloroimidazole, hydrochloride and 4- morpholine carbonyl chloride applying the general procedure 8. The crude product was puri- fied by flash chromatography (Quad flash 12, EtOAc) (54%, oil).

'H NMR (300MHz ; CDCI3) : my 3.58 (bs, 2H), 3.68 (bs, 2H), 3.69 (t, 4H), 6.94 (d, 1H), 7.10 (d, 1 H) ; HPLC-MS: m/z = 232.0 (M+1); Rt = 1.69 min.

Example 340 (General procedure 8) Morpholine-4-carboxylic acid 2-phenylsulfanyl-imidazol- 1-yl ester The title compound was prepared from 1-hydroxy-2-phenylsulfanylimidazole, hydrochloride and 4-morpholine carbonyl chloride applying the general procedure 8. The crude product

was purified by flash chromatography (Quad flash 12, EtOAc) (98%, oil).

'H NMR (300MHz ; CDC13) : zu 3.46 (bs, 4H), 3.66 (bs, 4H), 7.15 (d, 1H), 7.18-7. 31 (m, 6H); HPLC-MS: m/z = 306.1 (M+1); Rt = 2.75 min.

Example 341 (General procedure 8) Morpholine-4-carboxylic acid 2- (4-methoxy-phenyl)- imidazol-1-yl ester The title compound was prepared from 1-hydroxy-2- (4-methoxyphenyl) imidazole, hydrochlo- ride and 4-morpholine carbonyl chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc) (49%, crystals).

'H NMR (300MHz ; CDCI3) : 8 3.51 (bs, 2H), 3.62-3. 76 (m, 6H), 3.86 (s, 3H), 6.96 (d, 2H), 7.08 (d, 1H), 7.11 (d, 1 H), 7.70 (d, 2H); HPLC-MS : m/z= 304.1 (M+1) ; Rt = 1.81 min.

Example 342 (General procedure 8) Morpholine-4-carboxylic acid 4-bromo-pyrazol-1-yl ester The title compound was prepared from 1-hydroxy-4-bromopyrazole and 4-morpholine car- bonyl chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (85%, crystals).

'H NMR (300MHz ; CDCI3) : 9 3. 57 (bs, 2H), 3. 68 (bs, 2H), 3.79 (t, 4H), 7.35 (d, 1H), 7.43 (d, 1 H) ; HPLC-MS : m/z = 298.0 (M+23); Rt = 2.46 min.

Example 343 (General procedure 8) Morpholine-4-carboxylic acid 4-iodo-pyrazol-1-yl ester The title compound was prepared from 1-hydroxy-4-iodopyrazole and 4-morpholine carbonyl chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (99%, crystals).

'H NMR (300MHz ; CDCI3) : zu 3.56 (bs, 2H), 3.66 (bs, 2H), 3.77 (t, 4H), 7.41 (d, 1H), 7.44 (d, 1 H) ; HPLC-MS: m/z = 324.0 (M+1); Rt = 2.65 min.

Example 344 (General procedure 8) Morpholine-4-carboxylic acid 3,4, 5-tribromo-pyrazol-1-yl ester The title compound was prepared from 1-hydroxy-3,4, 5-tribromopyrazole and 4-morpholine carbonyl chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (90%, crystals).

1H NMR (300MHz ; CDCI3) : a 3.59 (bs, 2H), 3.69 (bs, 2H), 3.79 (t, 4H); HPLC-MS: m/z= 455.6 (M+23); Rt = 3.91 min.

Example 345 (General procedure 8) Morpholine-4-carboxylic acid 3- (4-methoxy-phenyl)-pyrazol-1-yl ester The title compound was prepared from 1-hydroxy-3- (4-methoxyphenyl) pyrazole and 4- morpholine carbonyl chloride applying the general procedure 8. The crude product was puri- fied by flash chromatography (Quad flash 12, EtOAc-heptane) (62%, crystals).

'H NMR (300MHz ; CDCI3) : a 3.58 (bs, 2H), 3.71 (bs, 2H), 3.79 (t, 4H), 3. 84 (s, 3H), 6.53 (d, 1 H), 6.92 (d, 2H), 7.40 (d, 1 H), 7.71 (d, 2H); HPLC-MS : m/z = 326.0 (M+23); Rt = 3.21 min.

Example 346 (General procedure 8) Morpholine-4-carboxylic acid 3-thiophen-2-yl-pyrazol-1- yl ester The title compound was prepared from 1-hydroxy-3- (2-thienyl) pyrazole and 4-morpholine carbonyl chloride applying the general procedure 8. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (75%, crystals).

'H NMR (300MHz ; CDCI3) : a 3.57 (bs, 2H), 3.69 (bs, 2H), 3.79 (t, 4H), 6.51 (d, 1 H), 7.04 (dd, 1 H), 7.26 (dd, 1 H), 7.34 (dd, 1 H), 7.40 (d, 1 H) ; HPLC-MS: m/z = 280.0 (M+1); Rt = 3.12 min.

Example 347 (General procedure 8) Morpholine-4-carboxylic acid pyrazol-1-yl ester The title compound was prepared from 1-hydroxypyrazole and 4-morpholine carbonyl chlo- ride applying the general procedure 8. The crude product was purified by flash chromatogra- phy (Quad flash 12, EtOAc-heptane) (94%, crystals).

'H NMR (300MHz ; CDCI3) : a 3.57 (bs, 2H), 3.69 (bs, 2H), 3.79 (t, 4H), 6.32 (t, 1H), 7.38 (dd, 1H), 7.41 (dd, 1H) ; HPLC-MS: m/z= 198.0 (M+1); Rt = 1. 18 min.

Example 348 (General procedure 16) 4-Methyl-piperazine-1-carboxylic acid pyrazol-1-yl es- ter The title compound was prepared from 1-hydroxypyrazole and N-methylpiperazine applying the general procedure 16. The crude product was purified by preparative HPLC (water- acetonitrile-0. 1 % TFA) (17%, salt with TFA).

'H NMR (300MHz ; CDCI3) : a 2.36 (s, 3H), 2.50 (bt, 4H), 3.59 (bs, 2H), 3.71 (bs, 2H), 6.31 (t, 1 H), 7.38 (dd, 1 H), 7.40 (dd, 1 H); HPLC-MS: m/z = 211.0 (M+1); Rt = 0.40 min.

Example 349 (General procedure 16) 4-Cyclopentyl-piperazine-1-carboxylic acid pyrazol-1-yl ester The title compound was prepared from 1-hydroxypyrazole and N-cyclopentylpiperazine ap- plying the general procedure 16. The crude product was purified by preparative HPLC (wa- ter-acetonitrile-0. 1% TFA) (34%, salt with TFA).

'H NMR (300MHz ; CDCI3) : a 1.45-2. 01 (m, 8H), 2.70 (bs, 4H), 2.92 (bs, 1H), 3.55 (bt, 1H), 3.63 (bs, 2H), 3.77 (bs, 2H), 6.31 (t, 1 H), 7.38 (dd, 1 H), 7.41 (dd, 1 H) ; HPLC-MS : m/z = 265.1 (M+1); Rt = 0.54 min.

Example 350 (General procedure 16) 4-Phenyl-piperazine-1-carboxylic acid pyrazol-1-yl es- ter The title compound was prepared from 1-hydroxypyrazole and N-phenylpiperazine applying the general procedure 16. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (48%, crystals).

1H NMR (300MHz ; CDCI3) : zu 3.25 (bt, 4H), 3.72 (bs, 2H), 3.85 (bs, 2H), 6.33 (t, 1H), 6.92- 6.98 (m, 3H), 7.27-7. 33 (m, 2H), 7.38 (dd, 1H), 7.41 (dd, 1H) ; HPLC-MS: m/z= 273.1 (M+1); Rt = 3.06 min.

Example 351 (General procedure 16) 4-Pyridin-2-yl-piperazine-1-carboxylic acid pyrazol-1-yl ester The title compound was prepared from 1-hydroxypyrazole and 1- (2-pyridyl) piperazine apply- ing the general procedure 16. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (59%, crystals). oh NMR (300MHz ; CDC13) : a 3. 62-3.85 (m, 8H), 6.32 (t, 1H), 6.66-6. 72 (m, 2H), 7.39 (dd, 1H), 7.42 (dd, 1H), 7.53 (dt, 1H), 8.21 (d, 1H) ; HPLC-MS: m/z= 274.1 (M+1); Rt= 0.63 min.

Example 352 (General procedure 16) 4-Pyrimidin-2-yl-piperazine-1-carboxylic acid pyrazol-1- yl ester

The title compound was prepared from 1-hydroxypyrazole and 1- (2-pyrimidyl) piperazine ap- plying the general procedure 16. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (57%, crystals).

'H NMR (300MHz ; CDC13) : s 3.65 (bs, 2H), 3.78 (bs, 2H), 3.95 (bs, 4H), 6.32 (t, 1 H), 6.58 (t, 2H), 7.38 (dd, 1 H), 7.42 (dd, 1 H), 8.35 (d, 1 H) ; HPLC-MS: m/z = 275.2 (M+1); Rt = 2. 14 min.

Example 353 (General procedure 16) 4-Benzo [1, 3] dioxol-5-yl-piperazine-1-carboxylic acid pyrazol-1-yl ester The title compound was prepared from 1-hydroxypyrazole and 1-Benzo [1,3] dioxol-5- ylpiperazine applying the general procedure 16. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (92%, crystals).

'H NMR (300MHz ; CDCI3) : a 3.11 (bt, 4H), 3.71 (bs, 2H), 3.83 (bs, 2H), 5.93 (s, 2H), 6.32 (t, 1 H), 6.39 (dd, 1 H), 6.57 (d, 1 H), 6.74 (d, 1 H), 7.37 (dd, 1 H), 7.41 (dd, 1 H) ; HPLC-MS: m/z = 317.2 (M+1); Rt = 2.96 min.

Example 354 (General procedure 16) 4-Benzyl-piperazine-1-carboxylic acid 4-iodo-pyrazol-1- yl ester The title compound was prepared from 1-hydroxy-4-iodopyrazole and 1-benzylpiperazine applying the general procedure 16. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (32%, oil).

'H NMR (300MHz ; CDCI3) : a 2.53 (bs, 4H), 3.57 (bs, 4H), 3.67 (bs, 2H), 7.28-7. 38 (m, 5H), 7.40 (d, 1 H), 7.43 (d, 1 H) ; HPLC-MS : m/z = 413.0 (M+1); Rt = 1.75 min.

Example 355 (General procedure 16) 4-Cyclopentyl-piperazine-1-carboxylic acid 4-iodo- pyrazol-1-yl ester The title compound was prepared from 1-hydroxy-4-iodopyrazole and N- cyclopentylpiperazine applying the general procedure 16. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane-3% Et3N) (61%, crystals).

'H NMR (300MHz ; Cd13) : 8 1.33-1. 94 (m, 8H), 2.46-2. 61 (m, 5H), 3.57 (bt, 2H), 3.67 (bt, 2H), 3.63 (bs, 2H), 3.77 (bs, 2H), 7.40 (d, 1H), 7.44 (d, 1H) ; HPLC-MS: m/z= 391.1 (M+1); Rt = 1.31 min.

Example 356 (General procedure 16) 4- (4-Fluoro-benzyl)-piperazine-1-carboxylic acid 4- iodo-pyrazol-1-yi ester The title compound was prepared from 1-hydroxy-4-iodopyrazole and 1- (4- fluorobenzyl) piperazine applying the general procedure 16. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (48%, crystals).

'H NMR (300MHz ; CDCI3) : a 2.50 (t, 4H), 3.51 (s, 2H), 3.57 (bt, 2H), 3.66 (bt, 2H), 7.02 (t, 2H), 7.29 (dd, 2H), 7.40 (d, 1 H), 7.43 (d, 1 H) ; HPLC-MS: m/z = 431.0 (M+1); Rt = 1.79 min.

Example 357 (General procedure 16) 4-Phenyl-piperazine-1-carboxylic acid 4-iodo-pyrazol- 1-yl ester The title compound was prepared from 1-hydroxy-4-iodopyrazole and N-phenylpiperazine applying the general procedure 16. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (52%, crystals).

'H NMR (300MHz ; CDCI3) : zu 3.25 (t, 4H), 3.72 (bs, 2H), 3.81 (bs, 2H), 6.90-6. 97 (m, 3H), 7.30 (t, 2H), 7.41 (d, 1H), 7.47 (d, 1H) ; HPLC-MS: m/z= 399.1 (M+1); Rt= 3.91 min.

Example 358 (General procedure 16) 4-Pyridin-2-yl-piperazine-1-carboxylic acid 4-iodo- pyrazol-1-yl ester The title compound was prepared from 1-hydroxy-4-iodopyrazole and 1- (2-pyridyl) piperazine applying the general procedure 16. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (45%, crystals).

'H NMR (300MHz ; CDCI3) : a 3.62-3. 82 (m, 8H), 6.66-6. 72 (m, 2H), 7.42 (d, 1H), 7.47 (d, 1 H), 7.54 (dt, 1 H), 8.22 (d, 1 H) ; HPLC-MS: m/z = 400.0 (M+1); Rt = 1.47 min.

Example 359 (General procedure 16) 4-Pyrimidin-2-yl-piperazine-1-carboxylic acid 4-iodo- pyrazol-1-yl ester The title compound was prepared from 1-hydroxy-4-iodopyrazole and 1- (2- pyrimidyl) piperazine applying the general procedure 16. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (10%, crystals).

'H NMR (300MHz ; Ceci3) : a 3.62 (bs, 2H), 3.72 (bs, 2H), 3.95 (bs, 4H), 6.58 (t, 2H), 7.41 (d, 1 H), 7.46 (d, 1 H), 8.36 (d, 1 H) ; HPLC-MS : m/z= 401.0 (M+1) ; Rt = 3.09 min.

Example 360 (General procedure 16) 4-Benzo [1,3] dioxol-5-yl-piperazine-1-carboxylic acid 4- iodo-pyrazol-1-yl ester The title compound was prepared from 1-hydroxy-4-iodopyrazole and 1-Benzo [1,3] dioxol-5- ylpiperazine applying the general procedure 16. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (59%, crystals).

'H NMR (300MHz ; CDCI3) : 8 3.11 (t, 4H), 3.69 (bs, 2H), 3.80 (bs, 2H), 5.92 (s, 2H), 6.38 (dd, 1 H), 6.56 (d, 1 H), 6.73 (d, 1 H), 7.41 (d, 1 H), 7.45 (d, 1 H) ; HPLC-MS: m/z = 443.0 (M+1); Rt = 3.79 min.

Example 361 4- (1-Ethylpropyl) piperazine-1-carboxylic acid 3-trifluoromethylphenyl ester hydrochloride salt To a stirred mixture of 1- (1-ethylpropyl) piperazine (175, u1, 1.0 mmol) and dry DCM (10 ml) was added 3-trifluoromethylphenyl chloroformate (250 mg, 1.1 mmol). The mixture was stirred over- night at room temperature and then diluted with DCM (50 ml). The reaction mixture was washed with 1 N NaOH (3 x 25 mi) and water (2 x 25 ml). The organic solution was concentrated and the residue was dissolved in a 0.5 N HCI solution (15 ml) and a small portion of acetonitrile. The acidic solution was concentrated and stirred with ethyl acetate (15 ml). The solid was isolated and dried to give 330 mg (86 %) of the title compound as a solid.

M. p. 260-261°C.

'H NMR (400 MHz, DMSO-d6) : 8 0.98 (t, 6H), 1.63 (hept, 2H), 1.86-1. 98 (m, 2H), 3.03-3. 12 (m, 1H), 3.12-3. 31 (m, 2H), 3.41-3. 49 (m, 2H), 3.52-3. 85 (m, 2H), 4.05-4. 35 (m, 2H), 7.47-7. 70 (m, 4H), 11.0 (brs, 1 H).

Example 362 4- (l-Ethylpropyl) piperazine-l-carboxylic acid naphthalen-1-yl ester hydrochloride salt To a stirred mixture of 1-(1-ethylpropyl) piperazine (175, ul, 1.0 mmol) and dry DCM (10 ml) was added 1-napthalenyl chloroformate (225 mg, 1.1 mmol). The mixture was stirred overnight at room temperature and then diluted with DCM (50 ml). The reaction mixture was washed with 1 N NaOH (3 x 25 ml) and water (2 x 25 ml). The organic solution was concentrated and the resi- due was dissolved in a 0.5 N HCI solution (15 mi) and a small portion of acetonitrile. The acidic solution was concentrated and stirred with ethyl acetate (15 ml). The solid was isolated and

dried to give 310 mg (85 %) of the title compound as a solid.

M. p. 288-290°C.

'H NMR (400 MHz, DMSO-d6) : 8 1. 00 (t, 6H), 1.63 (hept, 2H), 1.86-2. 02 (m, 2H), 3.07-3. 18 (m, 1H), 3.18-3. 42 (m, 2H), 3.42-3. 55 (m, 2H), 3.55-3. 73 (m, 1H), 3.78-3. 95 (m, 1H), 4. 05-4. 25 (m, 1H), 4. 35-4. 55 (m, 1H), 7.35 (d, 1H), 7.53 (t, 1H), 7.56-7. 7.61 (m, 2H), 7.85 (d, 1H), 7.90-8. 05 (m, 2H), 10.75 (brs, 1H).

Example 363 4- (1-Ethylpropyl) piperazine-1-carboxylic acid 4-fluorophenyl ester hydrochloride salt To a stirred mixture of 1- (1-ethylpropyl) piperazine (350, u1, 2.0 mmol) and dry DCM (15 ml) was added 4-fluorophenyl chloroformate (350 mg, 2.0 mmol). The mixture was stirred overnight at room temperature and then diluted with DCM (50 ml). The reaction mixture was washed with 1 N NaOH (3 x 25 ml) and water (2 x 25 ml). The organic solution was concentrated and the resi- due was re-evaporated twice with acetonitrile to give 590 mg of the free base. The hydrochlo- ride salt was prepared from 465 mg free base by addition of a 0.5 N HCI solution (15 ml) and a small portion of acetonitrile. The acidic solution was concentrated and stirred with ethyl acetate (15 ml). The solid was isolated and dried to give 470 mg (90 %) of the title compound as a solid.

M. p. 275-277°C.

'H NMR (400 MHz, DMSO-d6) : 8 0.98 (t, 6H), 1.64 (hept, 2H), 1.85-1. 95 (m, 2H), 3.02-3. 11 (m, 1H), 3.11-3. 28 (m, 2H), 3.38-3. 46 (m, 2H), 3.50-3. 80 (m, 2H), 4.00-4. 30 (m, 2H), 7.18-7. 26 (m, 4H), 10.85 (brs, 1 H).

Example 364 4- (1-Ethylpropyl) piperazine-1-carboxylic acid 2-nitrophenyl ester hydrochloride salt To a stirred mixture of 1- (1-ethylpropyl) piperazine (175 NI, 1.0 mmol) and dry DCM (10 ml) was added 2-nitrophenyl chloroformate (201 mg, 1.0 mmol). The mixture was stirred overnight at room temperature and then diluted with DCM (50 ml). The reaction mixture was washed with 1 N NaOH (3 x 25 ml) and water (2 x 25 ml). The organic solution was concentrated and the resi- due was dissolved in a 0.5 N HCI solution (15 ml). The acidic solution was concentrated and

stirred with ethyl acetate (15 ml). The solid was isolated and dried to give 310 mg (86 %) of the title compound as a solid.

M. p. 251-253°C.

1H NMR (400 MHz, DMSO-d6) : 8 0.96 (t, 6H), 1.65 (hept, 2H), 1.83-1. 95 (m, 2H), 3.06-3. 25 (m, 3H), 3.42-3. 53 (m, 2H), 3.53-3. 83 (m, 2H), 4.02-4. 13 (m, 1H), 4.20-4. 34 (m, 1H), 7.50-7. 55 (m, 2H), 7.83 (t, 1H), 8.13 (d, 1H), 10.9 (brs, 1H).

Example 365 4- (1-Ethylpropyl) piperazine-1-carboxylic acid 4-methoxycarbonylphenyl ester hy- drochloride salt To a stirred mixture of 1- (1-ethylpropyl) piperazine (350, ut, 2.0 mmol) and dry DCM (15 mi) was added 4-methoxycarbonylphenyl chloroformate (430 mg, 2.0 mmol). The mixture was stirred overnight at room temperature and then diluted with DCM (50 ml). The reaction mixture was washed with 1 N NaOH (3 x 25 ml) and water (2 x 25 ml). The organic solution was concen- trated and re-evaporated twice with acetonitrile. The residue was dissolved in a 0.5 N HCI solu- tion (15 mi) and a small portion of acetonitrile. The acidic solution was concentrated and stirred with ethyl acetate (15 ml). The solid was isolated and dried to give 670 mg (90 %) of the title compound as a solid.

M. p. 248°C decomp.

'H NMR (400 MHz, DMSO-d6) : 8 0.97 (t, 6H), 1.63 (hept, 2H), 1.85-1. 95 (m, 2H), 3.02-3. 11 (m, 1 H), 3.11-3. 30 (m, 2H), 3.40-3. 48 (m, 2H), 3.50-3. 80 (m, 2H), 3.85 (s, 3H), 4.05-4. 33 (m, 2H), 7.33 (d, 2H), 8.00 (d, 2H) ), 10.7 (brs, 1 H).

Example 366 Methyl-phenyl-carbamic acid 5- (3, 3-dimethyl-butyrylamino)-pyridin-2-yl ester A solution of N- (6-hydroxy-pyridin-3-yl)-3, 3-dimethyl-butyramide (0.42 g, 2.00 mmol), N- methyl-N-phenylcarbamoyl chloride (0.37 g, 2.20 mmol) and 1, 4-diazabicyclo [2,2, 2] octane (0.25 g, 2.20 mmol) in tetrahydrofuran (20 mL) was stirred at room temperature for 2.5 hours.

Water was added and the solution was extracted three times with dichloromethane. The combined organic layers were dried over sodium sulphate, filtered and evaporated in vacuo.

The residue was redissolved in ethyl acetate and the solution was filtered over a short pad of silicagel. Evaporation of the solvent and crystallisation of the solid from ethyl acetate: heptane yielded the title compound (0.54 g, 79% yield) as a white solid.

'H NMR (300MHz, CDCI3) : 8 = 1.03 (s, 9H), 2.15 (s, 2H), 3.47 (br. s, 3H), 6.91 (br. s, 1H), 7.27 (m, 1H), 7.38 (m, 4H), 7.99 (br. s + dd, 2H), 8.13 (d, 1H) ; HPLC-MS (Method A): m/z = 342 (M+H) + ; Rt = 3.67 min.

Example 367 Methyl-phenyl-carbamic acid 5-[(pyridine-2-carbonyl)-amino]-pyridin-2-yl ester A solution of pyridine-2-carboxylic acid (6-hydroxy-pyridin-3-yl)-amide hydrochloride (0.50 g, 1.99 mmol), N-methyl-N-phenylcarbamoyl chloride (0.44 g, 2.59 mmol) and 1,4- diazabicyclo [2,2, 2] octane (0.54 g, 4.81 mmol) in dimethylformamide (15 mL) was stirred at room temperature for 1 hour. Water was added and the solids were isolated by suction, re- dissolved in dichloromethane. The solution was dried over sodium sulphate, filtered and evaporated in vacuo. The residue was purified by flash column chromatography (Si02, ethyl acetate: heptane 50: 50) yielding the title compound (0.38 g, 55% yield) as a white solid.

'H NMR (300MHz, CDCI3) : 8 = 3.45 (br. s, 3H), 7.11 (br. s, 1 H), 7.26 (m, 1 H), 7.40 (d, 4H), 7.51 (m, 1H), 7.92 (dt, 1H), 8.28 (d, 1H), 8. 45 (dd, 1H), 8.60 (m, 2H), 10.10 (s, 1H) ; HPLC- MS (Method A): m/z = 349 (M+H) + ; Rt = 3.31 min.

Example 368 Methyl-phenyl-carbamic acid 2- (4, 4-dimethyl-2, 6-dioxo-piperidin-1-yl)-pyrimidin-5-yl ester A solution of 1- (5-hydroxy-pyrimidin-2-yl)-4, 4-dimethyl-piperidine-2, 6-dione (0.60 g, 2.55 mmol), N-methyl-N-phenylcarbamoyl chloride (0.48 g, 2.81 mmol) and 1, 4-diazabicyclo- [2,2, 2] octane (0.31 g, 2.81 mmol) in dichloromethane (25 mL) was stirred at room tempera- ture for 15 minutes. The solvent was evaporated in vacuo and the residue was purified by flash column chromatography (SiO2, ethyl acetate: heptane 50: 50), yielding the title com- pound as a white solid.

'H NMR (300MHz, CDCI3) : ô = 1.22 (s, 6H), 2.65 (s, 4H), 3.44 (br. s, 3H), 7.28-7. 48 (m, 5H), 8.68 (br. s, 2H); HPLC-MS (Method A): m/z = 369 (M+H) + ; Rt = 3.45 min.

Example 369 Methyl-phenyl-carbamic acid 5-bromo-pyrimidin-2-yl ester

A mixture of 4-bromo-2-hydroxypyrimidine (0.96 g, 5.49 mmol), N-methyl-N-phenylcarbamoyl chloride (1.02 g, 6.04 mmol) and 1, 4-diazabicyclo [2,2, 2] octane (0.68 g, 6.04 mmol) in dry tet- rahydrofuran (15mL) was stirred at room temperature for 1 hour. Dichloromethane was added and the solution was extracted twice with water. The organic layer was dried over so- dium sulphate, filtered and evaporated in vacuo yielding the title compound (1.70 g, 100% yield) as a white solid.

'H NMR (300MHz, CDCI3) : 8 = 3.43 (br. s, 3H), 7.27 (m, 1H), 7.38 (m, 4H), 8. 68 (br. s, 2H); HPLC-MS (Method A): m/z = 330 and 332 (M+H) + ; Rt = 3.33 min.

Example 370 Methyl-phenyl-carbamic acid 5-[(6-chloro-pyridine-3-carbonyl)-amino]-pyridin-2-yl ester A mixture of 4-chloro-N- (6-hydroxy-pyridin-3-yl)-nicotinamide (0.56 g, 2.25 mmol), N-methyl- N-phenylcarbamoyl chloride (0.51 g, 3.00 mmol) and 1, 4-diazabicyclo [2,2, 2] octane (0.67 g, 6.00 mmol) in dry tetrahydrofuran (15mL) was stirred at room temperature for 1 hour. Di- chloromethane was added and the solution was extracted twice with water. The organic layer was dried over sodium sulphate, filtered and evaporated in vacuo. The residue was purified by flash column chromatography (Si02, ethyl acetate: heptane 70: 30) followed by crystallised from ethyl acetate: heptane, yielding the title compound (44 mg, 5% yield) HPLC-MS (Method A): m/z = 383 (M+H) + ; Rt = 3.40 min.

Example 371 Methyl-phenyl-carbamic acid 5- (2, 2-dimethyl-propylcarbamoyl)-pyridin-2-yl ester A solution of N- (2, 2-dimethyl-propyl)-6-hydroxy-nicotinamide (0.50 g, 2.40 mmol), N-methyl- N-phenylcarbamoyl chloride (0.41 g, 2.40 mmol) and 1, 4-diazabicyclo [2,2, 2] octane (0.27 g, 2.40 mmol) in tetrahydrofuran (15 mL) was stirred at room temperature for 3 hours. The sol- vent was evaporated in vacuo and the residue was purified by flash column chromatography (first column : Si02, dichloromethane : ethyl acetate 95: 5, second column: Si02, ethyl acetate), yielding the title compound (0.43 g, 52% yield).

'H NMR (300MHz, Cd13) : 8 = 0.97 (s, 9H), 3.26 (d, 2H), 3.44 (br. s, 3H), 6.26 (br. s, 1H), 7.08 (br. s, 1H), 7.29 (m, 1H), 7.39 (m, 4H), 8.13 (br. d, 1H), 8.70 (br. s, 1H) ; HPLC-MS (Method A): m/z = 383 (M+H) + ; Rt = 3.40 min.

Example 372 [Methyl-phenyl-carbamic acid 6- (3, 4-dichloro-phenoxy)-pyridazin-3-yi ester A solution of 6- (3, 4-dichloro-phenoxy)-pyridazin-3-ol (0.51 g, 2.00 mmol), N-methyl-N- phenylcarbamoyl chloride (0. 36g, 2.10 mmol) and 1, 4-diazabicyclo [2,2, 2] octane (0.24 g, 2.10 mmol) in tetrahydrofuran (15 mL) was stirred at room temperature for 2 hours. The solvent was evaporated in vacuo and the residue was purified by flash column chromatography (SiO2, ethyl acetate: heptane 30: 70), yielding the title compound (0.34 g, 44% yield).

'H NMR (300MHz, CDCI3) : 8 = 3.43 (br. s, 3H), 7.10 (dd, 1H), 7.20-7. 51 (m, 9H); HPLC-MS (Method A): m/z = 389 (M+H) + ; Rt = 4.56 min.

Example 373 4- (tert-Butyl-dimethyl-silanyloxy)-piperidine-1-carboxylic acid 5-benzoylamino-pyridin-2-yl ester A solution of N- (6-hydroxy-pyridin-3-yl)-benzamide (214 mg, 1.00 mmol), 3- [4- (tert-butyl- dimethyl-silanyloxy)-piperidine-1-carbonyl]-1-methyl-3H-imid azol-1-ium iodide (451 mg, 1.00 mmol) and 1, 4-diazabicyclo [2,2, 2] octane (112 mg, 1.00 mmol) in dimethylformamide (10 mL) was stirred for 18 hours at room temperature followed by heating for 3 days at 40 °C. The solvent was evaporated in vacuo and the residue was purified by flash column chromatogra- phy (Si02, ethyl acetate: heptane 40: 60), yielding the title compound (364 mg, 77% yield) 'H NMR (300MHz, CDCI3) : s = 0.08 (s, 6H), 0.91 (s, 9H), 1.59 (m, 2H), 1.78 (m, 2H), 3.50 (m, 1 H), 3.62 (m, 2H), 3.76 (m, 1 H), 4.00 (m, 1 H), 6.87 (d, 1 H), 7.41 (m, 2H), 7.50 (m, 1 H), 7.90 (d, 2H), 8.01 (dd, 1 H), 8.36 (d, 1 H), 9.03 (s, 1 H, NH); HPLC-MS (Method A): m/z = 456 (M+H) + ; Rt = 5.23 min.

Example 374 4-Hydroxy-piperidine-1-carboxylic acid 5-benzoylamino-pyridin-2-yl ester Hydrofluoric acid (min. 40% in water, 0.50 mL) was added to a stirred solution of 4- (tert-butyl- dimethyl-silanyloxy)-piperidine-1-carboxylic acid 5-benzoylamino-pyridin-2-yl ester (364 mg, 0.77 mmol) in acetonitrile. After stirring overnight at room temperature the solvent was evaporated in vacuo. The residue was redissolved in dichloromethane. After addition of triethylamine (1 mL) the solution was filtered over a short pad of silicagel and washed with ethyl acetate: acetone 50: 50. Evaporation of the solvent yielded the title compound (180 mg,

68% yield) as a white solid.

'H NMR (400MHz, CDCl3 + DMSO-d6) : 8 = 1.60 (m, 2H), 1.91 (m, 2H), 3.25 (m, 2H), 4.02 (m, 1 H), 4.41 (d, 1 H), 7.07 (d, 1 H), 7.44-7. 61 (m, 3H), 7.99 (m, 2H), 8.35 (dd, 1 H), 8.72 (d, 1 H), 10.19 (s, 1H, NH); HPLC-MS (Method A): m/z = 342 (M+H) + ; Rt = 2.37 min.

Example 375 4-Hydroxy-piperidine-1-carboxylic acid 5-trifluoromethyl-pyridin-2-yl ester A solution of 2-hydroxy-5-trifluoromethylpyridine (0.32 g, 2.00 mmol), 4- (tert-butyl-dimethyl- silanyloxy)-piperidine-1-carboxylic acid 5-benzoylamino-pyridin-2-yl ester (0.90 g, 2.00 mmol) and triethylamine (0.20 g, 2.00 mmol) in acetonitrile (10 mL) was stirred at room temperature for three days. Hydrofluoric acid (min. 40% in water, 0.50 mL) was added and stirring was continued for 18 hours. The solvent was evaporated in vacuo and the residue was purified by flash column chromatography (SiO2, ethyl acetate: heptane 75: 25), followed by crystallisation from ethyl acetate: heptane, yielding the title compound (0.27 g, 47% yield) as a white solid.

H NMR (300MHz, CDCI3) : 8 = 1.64 (m, 3H, 2 x CH + OH), 1.96 (m, 2H), 3.33 (m, 1H), 3.45 (m, 1 H), 4.00 (m, 3H), 7.27 (d, 1 H), 8.00 (dd, 1 H), 8.64 (d, 1 H) ; HPLC-MS (Method A): m/z = 313 (M+Na) + ; Rt = 2. 45 min.

Example 376 4-Hydroxy-piperidine-1-carboxylic acid 5- (4-chloro-benzoylamino)-pyridin-2-yl ester A solution of 4-chloro-N- (6-hydroxy-pyridin-3-yl)-benzamide (0.50 g, 2.00 mmol), 4- (tert-butyl- dimethyl-silanyloxy)-piperidine-1-carboxylic acid 5-benzoylamino-pyridin-2-yl ester (0.90 g, 2.00 mmol) and triethylamine (0.20 g, 2.00 mmol) in dimethylformamide (10 mL) was stirred overnight at room temperature. The solvent was evaporated in vacuo. The residue was dis- solved in dichloromethane, filtered over a short pad of silicagel and washed with ethyl ace- tate: heptane 50: 50. The solvent was evaporated in vacuo and the residue was redissolved in acetonitrile and hydrofluoric acid (min. 40% in water, 0.50 mL) was added. After stirring overnight at room temperature the solvent was evaporated in vacuo. Dichloromethane and triethylamine (1 mL) were added and the solution was extracted twice with water, dried over sodium sulphate, filtered and evaporated in vacuo. Crystallisation from ethyl acetate: heptane yielded the title compound (321 mg, 43% yield).

1H NMR (300MHz, DMSO-d6) : 8 = 1.50 (m, 2H), 1.80 (m, 2H), 3.16 (m, 1H), 3.31 (m, 1H), 3.75 (m, 2H), 3.88 (m, 1H), 4. 81 (d, 1H), 7.18 (d, 1H), 7.62 (d, 2H), 8.01 (d, 2H), 8.24 (dd,

1H), 8.66 (d, 1H), 10.58 (s, 1H). ; HPLC-MS (Method A): m/z = 376 (M+H) + ; Rt = 2.81 min.

Example 377 4-Hydroxy-piperidine-1-carboxylic acid 5- (3-methoxy-benzoylamino)-pyridin-2-yl ester Starting from N-(6-hydroxy-pyridin-3-yl)-3-methoxy-benzamide (0.49 g, 2.00 mmol) and using the procedure as described in Example 376 yielded the title compound (347 mg, 47% yield). oh NMR (300MHz, CDCI3 + DMSO-d6) : 8 = 1.51 (m, 2H), 1.82 (m, 2H), 3.16 (m, 1H), 3.30 (m, 1H), 3.79 (s, 3H + m, 2H), 3.92 (m, 1H), 4.28 (br. s, 1H), 6.98 (m, 2H), 7.30 (t, 1H), 7.47 (m, 2H), 8.24 (dd, 1 H), 8.64 (d, 1 H), 10.04 (s, 1 H) ; HPLC-MS (Method A): m/z = 372 (M+H) + ; Rt = 2.58 min.

Example 378 4-Hydroxy-piperidine-1-carboxylic acid 5- (4-methoxy-benzoylamino)-pyridin-2-yl ester Starting from N-(6-hydroxy-pyridin-3-yl)-4-methoxy-benzamide (0.49 g, 2.00 mmol) and using the procedure as described in Example 376 yielded the title compound (297 mg, 40% yield).

'H NMR (300MHz, CDCI3) : 8 = 1.61 (m, 2H), 1.92 (m, 2H), 3.25 (m, 1H), 3.39 (m, 1H), 3.89 (s, 3H + m, 3H), 4.03 (m, 1 H), 6.96 (d, 2H), 7.06 (d, 1 H), 7. 98 (d, 2H), 8. 34 (dd, 1 H), 8.67 (d, 1 H), 9.72 (s, 1 H) ; HPLC-MS (Method A): m/z = 372 (M+H) + ; Rt = 2.53 min.

Example 379 4-Hydroxy-piperidine-1-carboxylic acid 5-(2, 4-dichloro-benzoylamino)-pyridin-2-yl ester Starting from 2, 4-dichloro-N-(6-dhydroxy-pyridin-3-yl)-benzamide (0.49 g, 2.00 mmol) and us- ing the procedure as described in Example 376 yielded the title compound (367 mg, 45% yield).

1H NMR (300MHz, CDCI3) : 8 = 1.62 (m, 2H), 1.90 (m, 2H), 3.24 (m, 1 H), 3.39 (m, 1 H), 3.88 (m, 3H), 4.01 (m, 1H), 7.03 (d, 1 H), 7.32 (d, 1H), 7.47 (s, 1H), 7.53 (d, 1 H), 8.28 (dd, 1H), 8.58 (d, 1H), 10.1 (s, 1 H) ; HPLC-MS (Method A): m/z = 410 and 412 (M+H) + ; Rt = 2.99 min.

Example 380 4-Hydroxy-piperidine-1-carboxylic acid 5- (4-trifluoromethyl-benzoylamino)-pyridin-2-yl ester Starting from N- (6-hydroxy-pyridin-3-yl)-4-trifluoromethyl-benzamide (0.56 g, 2.00 mmol) and

using the procedure as described in Example 376 yielded the title compound (367 mg, 45% yield).

'H NMR (300MHz, CDCI3) : â = 1.61 (m, 2H), 1.93 (m, 2H), 3.27 (m, 1H), 3.41 (m, 1H), 3.67 (br. s, 1H), 3.91 (m, 2H), 4.05 (m, 1H), 7.08 (d, 1H), 7.74 (d, 2H), 8.14 (d, 2H), 8.37 (dd, 1H), 8.67 (d, 1H), 10.11 (s, 1H) ; HPLC-MS (Method A) : m/z = 410 (M+H) + ; Rt= 3. 18 min.

Example 381 4-Hydroxy-piperidine-1-carboxylic acid 4, 4-dimethyl-2, 6-dioxo-3,4, 5,6-tetrahydro-2H- [1,3'] bipyridinyl-6'-yl ester A solution of 6'-hydroxy-4, 4-dimethyl-4, 5-dihydro-3H- [1, 3'] bipyridinyl-2, 6-dione (468 mg, 2.00 mmol), 4-(tert-butyl-dimethyl-silanyloxy)-piperidine-1-carboxylic acid 5-benzoylamino-pyridin- 2-yl ester (0.90 g, 2.00 mmol) and triethylamine (0.20 g, 2.00 mmol) in dimethylformamide (10 mL) was stirred at room temperature for 18 hours. The solvent was evaporated in vacuo.

The residue was dissolved in ethyl acetate, filtered over a short pad of silicagel and washed with ethyl acetate. The solvent was evaporated in vacuo and the residue was dissolved in 1 N HCI in ethyl acetate (10 mL, 10.0 mmol). After stirring for 1.5 hours at room temperature the solvent was evaporated in vacuo. The white solid was washed with a small amount of ethyl acetate and diethyl ether and dissolved in a few millilitres of dichloromethane and triethyl- amine (1 mL). Purification by flash column chromatography (SiO2, ethyl acetate: acetone 90: 10) yielded the title compound (182 mg, 25% yield) as a white solid.

'H NMR (300MHz, CDCI3) : 8 = 1.22 (s, 6H), 1.61 (m, 2H), 1.92 (m, 2H), 2.70 (s, 4H), 3.28 (m, 1 H), 3.40 (m, 1H), 3.63 (d, 1H), 3.84-4. 08 (m, 3H), 7.21 (d, 1H), 7.51 (dd, 1H), 8.07 (d, 1 H) ; HPLC-MS (Method A): m/z = 362 (M+H) + ; Rt = 2.25 min.

Example 382 Methyl-phenyl-carbamic acid 2, 6-oxo-3, 4,5, 6-tetrahydro-2H- [1, 3'] bipyridinyl-6'-yl ester A solution of N-methyl-N-phenyl carbamoyl chloride (170 mg, 1.00 mmol), 6'-hydroxy-4,5- dihydro-3H- [1, 3] bipyridinyl-2, 6-dione (206 mg, 1.00 mmol) and 1, 4-diazabicyclo [2,2, 2] octane (112 mg, 1.00 mmol) in tetrahydrofuran (10 mL) was stirred at room temperature for 18 hours. The solvent was evaporated in vacuo and the residue was purified by flash column chromatography (Si02, first ethyl acetate: heptane 75: 25 followed by pure ethyl acetate).

Evaporation of the solvent yielded the title compound (260 mg, 77% yield) as a white solid.

'H NMR (300MHz, CDC13) : 8 = 2.10 (quintet, 2H), 2.81 (t, 4H), 3.53 (br. s, 3H), 7.12 (br. s,

1 H), 7.27 (m, 1 H), 7.38 (m, 4H), 7.50 (d, 1 H), 8.09 (s, 1 H) ; HPLC-MS (Method A): m/z = 340 (M+H) + ; Rt = 2.89 min.

Example 383 Methyl-phenyl-carbamic acid 5-(2, 5-dioxo-pyrrolidin-1-yl)-pyridin-2-yl ester A solution of N-methyl-N-phenyl carbamoyl chloride (170 mg, 1.00 mmol), 1- (6-hydroxy- pyridin-3-yl)-pyrrolidine-2, 5-dione (192 mg, 1.00 mmol) and 1, 4-diazabicyclo [2,2, 2] octane (112 mg, 1.00 mmol) in tetrahydrofuran (10 mL) was stirred at room temperature for 4 hours.

The solvent was evaporated in vacuo and the residue was purified by flash column chroma- tography (Si02, ethyl acetate: heptane 80: 20) yielding the title compound (275 mg, 85% yield) as a white solid.

1H NMR (300MHz, CDC13) : 8 = 2.89 (s, 4H), 3.44 (br. s, 3H), 7.14 (br. s, 1H), 7.27 (m, 1H), 7.39 (m, 4H), 7.74 (br. d, 1 H), 8.38 (s, 1 H) ; HPLC-MS (Method A): m/z = 326 (M+H) + ; Rt = 2.78 min.

Example 384 Methyl-phenyl-carbamic acid 5- (4-trifluoromethyl-benzoylamino)-pyridin-2-yl ester A solution of N- (6-hydroxy-pyridin-3-yi)-4-trifluoromethyl-benzamide (1.41 g, 5.00 mmol), N- methyl-N-phenylcarbamoyl chloride (0.85 g, 5.00 mmol) and 1, 4-diazabicyclo [2,2, 2] octane (0.56 g, 5.00 mmol) in dimethylformamide (10 mL) was stirred at room temperature overnight . The solvent was evaporated in vacuo and the residue was purified by flash column chroma- tography (SiOz, ethyl acetate: heptane 50: 50) yielding the title compound (1.34 g, 64% yield) as a white solid.

1H NMR (300MHz, CDCI3) : 6 = 3.35 + 3.51 (2 x br. s, 3H), 6.83 (br. s, 1 H), 7. 24-7. 42 (m, 5H), 7.60 (d, 2H), 7.98 (d, 3H), 8.33 (s, 1H), 9.03 + 9. 18 (2 x br. s, 1H, NH); HPLC-MS (Method A): m/z = 416 (M+H) + ; Rt = 4.14 min.

Example 385 Methyl-phenyl-carbamic acid quinolin-6-yl ester A solution of 6-hydroxyquinoline (1. 00 g, 6.89 mmol), N-methyl-N-phenylcarbamoyl chloride (1.17 g, 6.89 mmol) and 1, 4-diazabicyclo [2,2, 2] octane (0.77 g, 6.89 mmol) in dichloro- methane (20 mL) was stirred at room temperature for 1.25 hours. More dichloromethane was

added and the solution was extracted with water. The organic layer was dried over sodium sulphate, filtered and evaporated in vacuo. The residue was purified by flash column chroma- tography (SiOz, ethyl acetate: heptane 50: 50). Evaporation of the solvent and recrystaillised from ethylacetate/heptane yielded the title compound (1.33 g, 69% yield) as a white solid.

'H NMR (300MHz, CDCI3) : 8 = 3.48 (s, 3H), 7.22-7. 64 (m, 8H), 8.09 (d, 2H), 8. 87 (m, 1H) ; HPLC-MS (Method A): m/z = 279 (M+H) + ; Rt = 2.56 min.

Example 386 4-Hydroxy-piperidine-1-carboxylic acid 5- (5-trifluoromethyl-pyridin-2-yloxy)-pyridin-2-yl ester A solution of 5- (5-trifluoromethyl-pyridin-2-yloxy)-pyridin-2-ol (180 mg, 0.70 mmol) ! 3- [4- (tert- butyl-dimethyl-silanyloxy)-piperidine-1-carbonyl]-1-methyl-3 H-imidazol-1-ium iodide (317 mg, 0.70 mmol) and triethylamine (98 uL) in acetonitrile (10 mL) was stirred at room temperature overnight. The solvent was evaporated in vacuo. The residue was redissolved in some di- chloromethane, filtered over a short pad of silicagel and washed with ethyl acetate: heptane 50: 50. The solvent was evaporated in vacuo and the residue was dissolved in 3.2N HCI in ether (10 mL). After stirring for 1 hour at room temperature the solvent was evaporated in vacuo and the residue was dissolved in dichloromethane. Triethylamine (0.5 mL) was added and the solution was extracted with water. The organic layer was dried over sodium sulphate, filtered and evaporated in vacuo to yield the title compound (174 mg, 65% yield) as a thick oil.

1H NMR (300MHz, CDCI3) : 8 1. 63 (m, 2H), 1.79 (br. s, 1H, OH), 1.97 (m, 2H), 3.31 (m, 1H), 3.43 (m, 1H), 3.89-4. 12 (m, 3H), 7.09 (d, 1H), 7.18 (d, 1H), 7.62 (dd, 1H), 7.94 (dd, 1H), 8.23 (d, 1 H), 8.39 (d, 1 H) ; HPLC-MS (Method A): m/z = 384 (M+H) + ; Rt = 3.00 min.

Example 387 4-Hydroxy-piperidine-1-carboxylic acid 5- (3, 5-dichloro-pyridin-2-yloxy)-pyridin-2-yl ester Starting from 5- (3, 5-dichloro-pyridin-2-yloxy)-pyridin-2-ol (265 mg, 1.03 mmol) and using the procedure as described in Example 386 yielded the title compound (121 mg, 54% yield) as a thick oil.

'H NMR (300MHz, CDCI3) : 8 = 1.62 (m, 2H), 1.94 (m, 2H), 3.06 (br. s, 1H), 3. 28 (m, 1H), 3.41 (m, 1H), 3.90 (m, 2H), 4.01 (m, 1H), 7.18 (d, 1H), 7.62 (dd, 1H), 7.79 (d, 1H), 7.94 (d, 1H), 8. 22 (d, 1 H). ; HPLC-MS (Method A): m/z = 384 (M+H) + ; Rt = 3.35 min.

Example 388 Methyl-phenyl-carbamic acid 5- (4-chloro-benzoylamino)-pyridin-2-yl ester A solution of 4-chloro-N- (6-hydroxy-pyridin-3-yl)-benzamide (0.50 g, 2.01 mmol), N-methyl-N- phenylcarbamoyl chloride (0.34 g, 2.01 mmol) and 1, 4-diazabicyclo [2,2, 2] octane (0.22 g, 0.34 mmol) in dimethylformamide (10 mmol) was stirred at room temperature for 2 hours.

Water (100 mL) was added and a thick oil was being formed. The water was decanted and the residue dissolved in dichloromethane, dried over sodium sulphate, filtered and evapo- rated in vacuo. Ethyl acetate was added and the solution was heated briefly (some of the compound does not dissolve). The solvent was decanted and heptane was added to it. After standing overnight, the crystals were isolated by suction, washed with heptane and dried in a vacuum oven at 45 °C. Further purification by flash column chromatography (SiO2, ethyl ace- tate: heptane 50: 50), yielded the title compound (0.41 g, 53% yield) as a white solid.

1H NMR (300MHz, CDCI3) : 8 = 3.38 (br. s, 3H), 6.84 (br. s, 1H), 7.20-7. 42 (m, 7H), 7.80 (d, 2H), 7.97 (dd, 1 H), 8.32 (d, 1 H), 9.09 (br. s, 1 H) ; HPLC-MS (Method A): m/z = 382 (M+H) + ; Rt = 3.63 min.

Example 389 4 Methyl-phenyl-carbamic acid 5- (4-methoxy-benzoylamino)-pyridin-2-yl ester A solution of N- (6-hydroxy-pyridin-3-yi)-4-methoxy-benzamide (1.22 g, 5.00 mmol), N-methyl- N-phenylcarbamoyl chloride (0.85 g, 5.00 mmol) and 1, 4-diazabicyclo [2,2, 2] octane (0.56 g, 5.00 mmol) in dimethylformamide (20 mL) was stirred at room temperature for 2 hours. Water (100 mL) was added. The solids were isolated by suction and washed with water. Crystallisa- tion from ethyl acetate: heptane yielded the title compound (1.08 g, 57% yield).

H NMR (300MHz, CDC13) : 8 = 3.42 (br. s, 3H), 3.86 (s, 3H), 6.89 (d, 2H + br. s, 1H), 7.27 (m, 1H), 7.39 (m, 4H), 7.84 (d, 2H), 8.11 (dd, 1H), 8.34 (d, 1H), 8.51 (br. s, 1H) ; HPLC-MS (Method A): m/z = 378 (M+H) + ; Rt = 3.55 min.

Example 390 Methyl-phenyl-carbamic acid 4,4-dimethyl-3,4,5,6-tetrahydro-2H-[1,3']bipyridinyl-6'-yl ester A solution of 4, 4-dimethyl-3, 4,5, 6-tetrahydro-2H- [1, 3'] bipyridinyl-6'-ol (0.86 g, 4.17 mmol), N- methyl-N-phenylcarbamoyl chloride (0.71 g, 4.17 mmol) and 1, 4-diazabicyclo [2,2, 2] octane (0.47 g, 4.17 mmol) in dichloromethane (10 mL) was stirred at room temperature for 2 hours.

Extra dichloromethane was added and the solution was washed with water, dried over so- dium sulphate, filtered and evaporated in vacuo. Crystallisation from ethyl acetate: heptane yielded the title compound (0.58 g, 41 % yield) 'H NMR (300MHz, CDCI3) : 8 = 0.99 (s, 6H), 1.52 (m, 4H), 3.16 (m, 4H), 3.43 (br. s, 3H), 6.92 (br. d, 1 H), 7.20-7. 41 (m, 6H), 7.98 (d, 1 H) ; HPLC-MS (Method A): m/z = 340 (M+H) + ; Rt = 4.21 min.

Example 391 Methyl-phenyl-carbamic acid 2-methyl-quinolin-6-yl ester A solution of 2-methylquinolin-6-ol (1. 00 g, 6.28 mmol), N-methyl-N-phenylcarbamoyl chlo- ride (1.07 g, 6.28 mmol) and 1, 4-diazabicyclo [2,2, 2] octane (0.70 g, 6.28 mmol) in dichloro- methane (10 mL) was stirred at room temperature for 18 hours. Extra dichloromethane was added and the solution was extracted twice with water, dried over sodium sulphate and fil- tered. Some ethyl acetate and heptane were added and the solution was slowly evaporated in vacuo yielding the title compound (1.64 g, 89% yield) as a white solid.

'H NMR (300MHz, CDCI3) : 8 = 2.71 (s, 3H), 3.45 (br. s, 3H), 7.25 (m, 2H), 7.40 (m, 5H), 7.54 (s, 1H), 7.98 (t, 2H); HPLC-MS (Method A): m/z = 293 (M+H) + ; Rt = 2.16 min.

Example 392 (General procedure 17) {2- [4- (Methyl-phenyl-carbamoyloxy)-phenyl]-ethyll- carbamic acid tert-butyl ester Tyramin was N-Boc protected as described in J. Org. Chem, 49,1984, 1016. To a solution of the N-Boc protected tyramin (10 mmol) in CH2CI2 (50 mL) was added N-methyl-N-. phenylcarbamoyl chloride (15 mmol) and DABCO (15 mmol) at room temperature. The reac- tion mixture was stirred for 16 hours at rt, added CH2CI2 (20 mL) and washed with aqueous citric acid (5%) and brine. The organic phase was separated, dried (MgS04) and evaporated to give the crude product which was purified by FC (Quad flash 40 MeOH-CH2CI25 : 95) to give 3.45 g (93%) of the title compound as colorless crystals.

HPLC-MS: m/z = 393.4 (M+Na); Rt = 4.44 min.

Example 393 (General procedure 17) Methyl-phenyl-carbamic acid 4- (2-amino-ethyl) phenyl ester {2- [4- (Methyl-phenyl-carbamoyloxy)-phenyl]-ethyl}-carbamic acid tertbutyl ester (3.7 g; 10

mmol) from above was dissolved in CH2CI2 (90 mL). Addition of TFA (6 mL) and stirring for 4 h. The reaction mixture was evaporated to dryness and dried in vacuo at 50 °C overnight producing the title compound as a TFA salt in quantitative yield as yellow hygroscopic crys- tals.

HPLC-MS: m/z = 271.1 (M+1); Rt = 2.17 min.

Example 394 (General procedure 17) Methyl-phenyl-carbamic acid 4- [2- (toluene-4- sulfonylamino)-ethyl]-phenyl ester The title compound was prepared in 39% yield as a clear oil using toluenesulfonyl chloride as the aryl sulfonyl chloride.

HPLC-MS: m/z= 425.2 (M+1); Rt = 4.33 min.

Example 395 (General procedure 17) Methyl-phenyl-carbamic acid 4- [2- (5-dimethylamino- naphthalene-1-sulfonylamino)-ethyl]-phenyl ester The title compound was prepared in 29% yield as a yellow fluorescent oil using 5- dimethylamino-naphthalene-1-sulfonyl chloride as the aryl sulfonyl chloride.

HPLC-MS: m/z = 505.1 (M+1); Rt = 4.58 min.

Example 396 (General procedure 17) Methyl-phenyl-carbamic acid 4- [2- (3, 4-difluoro- benzenesulfonylamino)-ethyl]-phenyl ester The title compound was prepared in 40% yield as a clear oil using 3, 4-difluoro- benzenesulfonyl chloride as the aryl sulfonyl chloride.

HPLC-MS: m/z= 447.1 (M+1); Rt = 4.47 min.

Example 397 (General procedure 17) 2- {2- [4- (Methyl-phenyl-carbamoyloxy)-phenyl]- ethylsulfamoyl}-benzoic acid methyl ester The title compound was prepared in 30% yield as an oil using 2-chlorosulfonyl-benzoic acid methyl ester as the aryl sulfonyl chloride.

HPLC-MS: m/z= 469.1 (M+1); Rt = 4.37 min.

Example 398 (General procedure 17) Methyl-phenyl-carbamic acid 4- [2- (2, 5-dichloro-

thiophene-3-sulfonylamino)-ethyl]-phenyl ester The title compound was prepared in 39% yield as an oil using 2, 5-dichloro-thiophene-3- sulfonyl chloride as the aryl sulfonyl chloride.

HPLC-MS : m/z = 487.0 (M+1) ; Rt = 4.80 min.

Example 399 (General procedure 17) Methyl-phenyl-carbamic acid 4- [2- (5-pyridin-2-yl- thiophene-2-sulfonylamino)-ethyl]-phenyl ester The title compound was prepared in 12% yield as crystals using 5-pyridin-2-yl-thiophene-2- sulfonyl chloride as the aryl sulfonyl chloride.

HPLC-MS: m/z = 494.0 (M+1); Rt = 4.42 min.

Example 400 (General procedure 17) Methyl-phenyl-carbamic acid 4- [2- (1-methyl-1 H- imidazole-4-sulfonylamino)-ethyl]-phenyl ester The title compound was prepared in 42% yield as a yellow oil using 1-methyl-1 H-imidazole-4- sulfonyl chloride as the aryl sulfonyl chloride.

HPLC-MS: m/z = 415. 1 (M+1); Rut=3. 31 min.

Example 401 (General procedure 17) Methyl-phenyl-carbamic acid 4- [2- (5-chloro-1, 3- dimethyl-1 H-pyrazole-4-sulfonylamino)-ethyl]-phenyl The title compound was prepared in 22% yield as an oil using 5-chloro-1, 3-dimethyl-1 H- pyrazole-4-sulfonyl chloride as the aryl sulfonyl chloride.

HPLC-MS : m/z= 463. 1 (M+1) ; Rt = 3.91 min.

Example 402 (General procedure 17) Methyl-phenyl-carbamic acid 4- [2- (4-nitro- benzenesulfonylamino)-ethyl]-phenyl ester The title compound was prepared in 25% yield as a yellow oil using 4-nitro-benzenesulfonyl chloride as the aryl sulfonyl chloride.

HPLC-MS: m/z = 456.0 (M+1) ; Rt = 4.19 min.

Example 403 (General procedure 17) Methyl-phenyl-carbamic acid 4- [2- (6-chloro-

imidazo [2,1-b] thiazole-5-sulfonylamino)-ethyl]-phenyl ester The title compound was prepared in 18% yield as an oil using 6-chloro-imidazo [2,1- b] thiazole-5-sulfonyl chloride as the aryl sulfonyl chloride.

HPLC-MS : m/z = 490.9 (M+1) ; Rt = 3.90 min.

Example 404 (General procedure 17) Methyl-phenyl-carbamic acid 4- [2- (2-trifluoromethoxy- benzenesulfonylamino)-ethyl]-phenyl ester The title compound was prepared in 38% yield as an oil using 2-trifluoromethoxy- benzenesulfonyl chloride as the aryl sulfonyl chloride.

HPLC-MS: m/z= 495.1 (M+1) ; Rt = 4.49 min.

Example 405 (General procedure 17) Methyl-phenyl-carbamic acid 4- (2-dimethylaminosulfonylamino-ethyl)-phenyl ester The title compound was prepared in 32% yield as an oil using dimethylaminosulfamoyl chlo- ride as the sulfonyl chloride.

HPLC-MS: m/z= 378.1 (M+1); Rt = 3.62 min.

Example 406 (General procedure 17) Methyl-phenyl-carbamic acid 4- (2- methanesulfonylamino-ethyl)-phenyl ester The title compound was prepared in 22% yield as an oil using methanesulfonyl chloride as the sulfonyl chloride.

HPLC-MS: m/z = 349.0 (M+1); Rt = 3.26 min.

Example 407 (General procedure 17) Methyl-phenyl-carbamic acid 4- [2- (6-morpholin-4-yl- pyridine-3-sulfonylamino)-ethyl]-phenyl ester The title compound was prepared in 55% yield as crystals using 6-morpholin-4-yl-pyridine-3- sulfonyl chloride as the aryl sulfonyl chloride.

HPLC-MS: m/z = 497.0 (M+1); Rt = 3.90 min.

Example 408 (General procedure 17) Methyl-phenyl-carbamic acid 4- [2- (6-phenoxy-pyridine- 3-sulfonylamino)-ethyl]-phenyl ester

The title compound was prepared in 54% yield as crystals using 6-phenoxy-pyridine-3- sulfonyl chloride as the aryl sulfonyl chloride.

HPLC-MS : m/z = 504.4 (M+1) ; Rt = 4.45 min.

Example 409Methyl-phenyl-carbamic acid 4- {2- [4- (4-methyl-piperazin-1-yl)- benzenesulfonylamino]-ethyl}-phenyl ester To a stirred solution of 1- (4-bromophenyl)-4-methylpiperazine (2.05 g, 8.0 mmol) in THF (10 mL) was added dropwise 1. 57 M solution in hexanes n-BuLi (4.6 mL, 7.2 mmol) over a 5-min period at-78°C. The mixture was stirred at-78°C for 15 min. Then gaseous sulphur dioxide (ca. 5 g) was added causing an immediate precipitation. The mixture was allowed to warm to room temperature and stirred for 1 h. The precipitated lithium ; 4- (4-methyl-piperazin-1-yl)- benzenesulfinate was isolated by filtration under N2 (g), washed with THF (20 mL) and dried in vacuo providing 1.83 g (96%) of the lithium sulfinat as a solid. This lithium sulfinat (83 mg, 0.34 mmol) was suspended in CH2CI2 (1 mL) and stirred with NCS (45 mg, 0.34 mmol) for 10 min at rt. A solution of N-methyl-N-phenyl-carbamic acid 4- (2-amino-ethyl) phenyl ester as its TFA salt (0.26 mmol) in CH2CI2 (1.5 mL) was added together with DIPEA (0.90 mmol).

The mixture was stirred at rt for 16 h and quenched with HOAc (2 mL) and water (2 mL). Ex- traction with CH2CI2 and drying of the combined organic extracts gave the crude product which was purified by preparative HPLC (Gilson). This gave 54 mg (33%) of the title com- pound as its TFA salt as colorless crystals.

HPLC-MS: milz = 509. 0 (M+1); Rt = 2.88 min.

Example 410Methyl-phenyl-carbamic acid 4- [2- (4-dimethylamino-benzenesulfonylamino)- ethyl]-phenyl ester To a stirred solution of (4-bromo-phenyl)-dimethylamine (4.02 g, 20 mmol) in THF (25 mL) was added dropwise 1.57 M solution in hexanes n-BuLi (11.5 mL, 18 mmol) over a 5-min pe- riod at-78°C. The mixture was stirred at-78°C for 15 min. Then gaseous sulphur dioxide (ca.

5 g) was added causing an immediate precipitation. The mixture was allowed to warm to room temperature and stirred for 1 h. The precipitated lithium sulfinat was isolated by filtra- tion under N2 (g), washed with THF (20 mL) and dried in vacuo providing 2.99 g (87%) of lith- ium; 4-dimethylamino-benzenesulfinate as a bluegreen solid. This lithium sulfinat (65 mg, 0.34 mmol) was suspended in CH2CI2 (1 mL) and stirred with NCS (45 mg, 0.34 mmol) for 10 min at rt. A solution of N-methyl-N-phenyl-carbamic acid 4- (2-amino-ethyl) phenyl ester as its TFA salt (0.26 mmol) in CH2CI2 (1.5 mL) was added together with DIPEA (0.90 mmol). The

mixture was stirred at rt for 16 h and quenched with HOAc (2 mL) and water (2 mL). Extrac- tion with CH2CI2 and drying of the combined organic extracts gave the crude product which was purified by preparative HPLC (Gilson). This gave 37 mg (31 %) of the title compound as an oil.

HPLC-MS: m/z = 454.5 (M+1); Rt = 4.16 min.

Example 411 Methyl-phenyl-carbamic acid 4- {2- [4- (2-pyrrolidin-1-yl-ethoxy)-benzenesulfonylamino]-ethyl}- phenyl ester To a stirred solution of 1- [2- (4-bromo-phenoxy)-ethyl]-pyrrolidine (6.72 g, 25 mmol) in THF (45 mL) was added dropwise 1.6 M solution in hexanes n-BuLi (14 mL, 22.4 mmol) over a 5- min period at-78°C. The mixture was stirred at-78°C for 15 min. Then gaseous sulphur diox- ide (ca. 6 g) was added causing an immediate precipitation. The mixture was allowed to warm to room temperature and stirred for 1 h. The precipitated lithium sulfinate was isolated by filtration under N2 (g), washed with THF (40 mL) and dried in vacuo providing 5.04 g (78%) of lithium ; 4- (2-pyrrolidin-1-yl-ethoxy)-benzenesulfinate as a solid. This lithium sulfi- nate (179 mg, 0.69 mmol) was suspended in CH2C12 (2 mL) and stirred with NCS (80 mg, 0.60 mmol) for 10 min at rt. A solution of N-methyl-N-phenyl-carbamic acid 4- (2-amino- ethyl) phenyl ester as its TFA salt (0.55 mmol) in CH2CI2 (3 mL) was added together with DIPEA (2.0 mmol). The mixture was stirred at rt for 16 h and evaporated to dryness. It was then redissolved in MeCN and purified by preparative HPLC (Gilson). This gave 89 mg (25%) of the title compound as its TFA salt as a crystals.

HPLC-MS : m/z = 524.5 (M+1); Rt = 3.04 min.

Example 412 (General procedure 15) 4- (Tetrahydrofuran-2-ylmethyl)-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2- yloxy)-phenyl ester The hydrochloride of the title compound was prepared from 4- (5-trifluoromethyl-pyridin-2- yloxy)-phenyl chloroformate and 1- (tetrahydrofuran-2-ylmethyl)-piperazine, crude yield 0.28 g (89%). The crude product was stirred with a mixture of ethyl acetate (10 mi) and a solution of sodium bicarbonate (0. 05 g) in water (5 ml). The aqueous layer was extracted with ethyl ace- tate (10 + 5 ml), the combined organic phases were washed with brine (5 MI), dried over so- dium sulfate, filtered and evaporated. The residue was triturated with heptane (3 ml), filtered and dried to give the title compound, White crystals, m. p. 98-100 °C ;'H NMR (CDCI3) 9

8.52-8. 37 (br, 1 H), 7.98-7. 83 (dd, 1 H), 7.25-7. 06 (m, 4H), 7.00 (d, J = 8.5 Hz), 4.18-3. 47 (m, 7H), 2.76-2. 36 (m, 6H), 2.13-1. 74 (m, 3H), 1.64-1. 40 (m, 1 H) ; IR (KBr): v 1715 (C=O) cm Example 413 (General procedure 15) 4-Cyclopropylmethyl-piperazine-1-carboxylic acid 4- (3-chloro-5-trifluoromethyl-pyridin-2- yloxy)-phenyl ester The hydrochloride of the title compound was prepared from 4- (3-chloro-5-trifluoromethyl- pyridin-2-yloxy)-phenyl chloroformate and 1-cyclopropylmethyl-piperazine, yield 83%. White crystals, m. p. 254-255°C ; IR (KBr): v 1728 (C=O) cm~1.

Example 414 (General procedure 15) 4-(Tetrahydro-furan-2-ylmethyl)-piperazine-1-carboxylic acid 4- (4-trifluoromethylphenoxy)- phenyl ester The hydrochloride of the title compound was prepared from 4- (4-trifluoromethyl-phenoxy)- phenyl chloroformate and 1- (tetrahydro-furan-2-ylmethyl)-piperazine, yield 93%. White crys- tals, m. p. 216-217°C ; IR (KBr): v 1730 (C=O) cm'.

Example 415 (General procedure 15) 4-Cyclohexylmethyl-piperazine-1-carboxylic acid 4- (4-trifluoromethyl-phenoxy)-phenyl ester The hydrochloride of the title compound was prepared from 4- (4-trifluoromethyl-phenoxy)- phenyl chloroformate and 1-cyclohexylmethyl-piperazine, yield 93%. White crystals, m. p.

256-258 °C ; IR (KBr): v 1715 (C=O) cm~1.

Example 416 (General procedure 15) 4-Cyclohexylmethyl-piperazine-1-carboxylic acid 4- (3-chloro-5-trifluoromethyl-pyridin-2- yloxy)-phenyl ester The hydrochloride of the title compound was prepared from 4- (3-chloro-5-trifluoromethyl- pyridin-2-yloxy)-phenyl chloroformate and1-cyclohexylmethyl-piperazine, yield 76%. White crystals, m. p. 265-266 °C ; IR (KBr) : v 1732 (C=O) cm~1.

Example 417 (General procedure 15) 4-Cyclopropylmethyl-piperazine-1-carboxylic acid 4- (4-trifluoromethyl-phenoxy)-phenyl ester The hydrochloride of the title compound was prepared from 4- (4-trifluoromethyl-phenoxy)- phenyl chloroformate and 1-cyclopropylmethyl-piperazine, yield 43%. White crystals, m. p.

238-239°C ; IR (KBr): v 1725 (C=O) cm~1.

Example 418 (General procedure 15) 4-(Tetrahydrofuran-2-ylmethyl)-piperazine-1-carboxylic acid 4- (3-chloro-5-trifluoromethyl- pyridin-2-yloxy)-phenyl ester The hydrochloride of the title compound was prepared from 4- (3-chloro-5-trifluoromethyl- pyridin-2-yloxy)-phenyl chloroformate and 1- (tetrahydrofuran-2-ylmethyl)-piperazine, yield 23%. White crystals, m. p. 98-100 °C ; IR (KBr): v 1731 (C=O) cm'.

Example 419 (General procedure 15) 4-Naphthalen-1-ylmethyl-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)- phenyl ester The hydrochloride of the title compound was prepared from 4- (5-trifluoromethyl-pyridin-2- yloxy)-phenyl chloroformate and 1-naphthalen-1-ylmethyl-piperazine, yield 71 %. White crys- tals, m. p. 218-219 °C ; IR (KBr): v 1713 (C=O) cm~1.

Example 420 (General procedure 15) 4-(2-Cyclohexyl-ethyl)-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)- phenyl ester The hydrochloride of the title compound was prepared from 4- (5-trifluoromethyl-pyridin-2- yloxy)-phenyl chloroformate and 1- (2-cyclohexyl-ethyl)-piperazine, yield 90%. White crystals, m. p. 274-276 °C ; IR (KBr): v 1715 (C=O) cm~1.

Example 421 (General procedure 15) 4- (3-Methoxy-phenyl)-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)- phenyl ester The title compound was prepared from 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl chlorofor-

mate and 1- (3-methoxy-phenyl)-piperazine, yield 96%. White solid, m. p. 109-111 °C ; IR (KBr) : v 1721 (C=O) cm'.

Example 422 (General procedure 15) 4-Cyclopropylmethyl-piperazine-1-carboxylic acid 4- [2- (4-chloro-phenyl)-ethylcarbamoyl]- phenyl ester The title compound was prepared from 4- [2- (4-chloro-phenyl)-ethylcarbamoyl]-phenyl chloro- formate and 1-cyclopropylmethyl-piperazine, yield 18%. White crystals, m. p. 225-226 °C ; IR (KBr): v 1710 (ester C=O), 1661 (amide C=O) cm~1.

Example 423 (General procedure 15) 4-(Tetrahydro-furan-2-ylmethyl)-piperazine-1-carboxylic acid 4- [2- (4-chloro-phenyl)- ethylcarbamoyl]-phenyl ester The title compound was prepared from 4- [2- (4-chloro-phenyl)-ethylcarbamoyl]-phenyl chloro- formate and 1- (tetrahydrofuran-2-ylmethyl)-piperazine, yield 12%. White crystals, m. p. 220- 221 °C ; IR (KBr): v 1708 (ester C=O), 1660 (amide C=O) cm~1.

Example 424 (General procedure 15) 4- (3, 4-Dichloro-benzyl)-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)- phenyl ester The hydrochloride of the title compound was prepared from 4- (5-trifluoromethyl-pyridin-2- yloxy)-phenyl chloroformate and 1- (3, 4-dichloro-benzyl)-piperazine, yield 86%. White crys- tals, m. p. 229-230 °C ; IR (KBr): v 1717 (C=O) cm~1.

Example 425 (General procedure 15) 4-Cyclopropylmethyl- (1, 4] diazepane-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)- phenyl ester The hydrochloride of the title compound was prepared from 4- (5-trifluoromethyl-pyridin-2- yloxy)-phenyl chloroformate and 1-cyclopropylmethyl- [1, 4] diazepane, yield 61%. White crys- tals, m. p. 208-209 °C ; IR (KBr) : v 1711 (C=O) cm'.

Example 426 (General procedure 15) 4-(2-Pyridin-2-yl-ethyl)-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)- phenyl ester The hydrochloride of the title compound was prepared from 4- (5-trifluoromethyl-pyridin-2- yloxy)-phenyl chloroformate and 1-(2-Pyridin-2-yl-ethyl)-piperazine, yield 81%. White crystals, m. p. 281-282 °C ; IR (KBr): v 1713 (C=O) cm-1.

Example 427 (General procedure 18) 4-(Pyrazin-2-yl)-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester The title compound was prepared from 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl chlorofor- mate and 1- (pyrazin-2-yl)-piperazine- White crystals, m. p. 160-161 °C ; HPLC-MS: m/z = 446 (M+1) at Rt = 4.0 min. ; 1H NMR (DMSO-d6) : 8 8.60-8. 57 (m, 1H), 8.39-8. 36 (m, 1H), 8.27- 8. 22 (dd-like, 1H), 8.14-8. 11 (m, 1H) 7.91-7. 87 (d-like, 1H), 7.29-7. 21 (m, 5H), 3.80-3. 64 (br, 6H), 3.64-3. 50 (br, 2H) ; IR (KBr): v 1737,1714 (C=O) cm~1.

Example 428 (General procedure 15) 4-(Benzo-isothiazol-3-yl)-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)- phenyl ester The hydrochloride of the title compound was prepared from 4- (5-trifluoromethyl-pyridin-2- yloxy)-phenyl chloroformate and 1- (benzo-isothiazol-3-yl)-piperazine. Drying on a rotary evaporator of the crude product gave the title compound as the free base. Purification by flash chromatography (silica, ethyl acetate-heptane 1: 4) gave white crystals, m. p. 132-133 °C ; IR (KBr): v 1726 (C=O) cm~1.

Example 429 (General procedure 15) 4- (5-Chloro-thiophen-2-ylmethyl)-piperazine-l-carboxylic acid 4- (5-trifluoromethyl-pyridin-2- yloxy)-phenyl ester The hydrochloride of the title compound was prepared from 4- (5-trifluoromethyl-pyridin-2- yloxy)-phenyl chloroformate and 1- (5-chloro-thiophen-2-ylmethyl)-piperazine, yield 48 %.

White crystals, m. p. 225-226 °C (from EtOH) ;'H NMR (DMSO-d6) : (5 12.00 (br, 1H), 8.60- 8.55 (1 H), 8.27-8. 21 (dd-like, 1 H), 7.33-7. 20 (m, 6H), 7.20-7. 15 (d, 1 H), 4.55 (br s, 2H),

4.40-4. 00 (br, 2H), 3.74-3. 27 (br, 4H + H2O) ; 3.27-2. 97 (br, 2H) ; IR (KBr): v 1723 (C=O) cm Example 430 (General procedure 15) <BR> <BR> <BR> 4- (3-Trifluoromethyl-phenyl)-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)- phenyl ester The hydrochloride of the title compound was prepared from 4- (5-trifluoromethyl-pyridin-2- yloxy)-phenyl chloroformate and 1- (3-trifluoromethyl-phenyl)-piperazine. The crude product was converted to the free base, yield 56%. White crystals, m. p. 87-88 °C ; IR (KBr): v 1719 (C=O) cm~1.

Example 431 (General procedure 15) 4- (5-Chloro-2-methyl-phenyl)-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2- yloxy)-phenyl ester The hydrochloride of the title compound was prepared from 4- (5-trifluoromethyl-pyridin-2- yloxy)-phenyl chloroformate and 1- (5-chloro-2-methyl-phenyl)-piperazine The crude product was converted to the free base, yield 26%. White crystals ; HPLC-MS: m/z = 492 (M+H) at Rt = 5.5 min. ; IR (KBr): v 1722 (C=O) cm'.

Example 432 (General procedure 15) 4- (1-Methyl-piperidin-4-ylmethyl)-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2- yloxy)-phenyl ester The dihydrochloride of the title compound was prepared from 4- (5-trifluoromethyl-pyridin-2- yloxy)-phenyl chloroformate and 1- (1-methyl-piperidin-4-ylmethyl)-piperazine, yield 6%.

White crystals, m. p. 305-306 °C ; IR (KBr): v 1713 (C=O) cm-1.

Example 433 (General procedure 15) 4-Biphenyl-4-ylmethyl- [1, 4] diazepane-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)- phenyl ester The hydrochloride of the title compound was prepared from 4- (5-trifluoromethyl-pyridin-2- yloxy)-phenyl chloroformate and 1-biphenyl-4-ylmethyl- [1, 4] diazepane. The crude product

was converted to the free base, yield 17%. White crystals, m. p. 143 °C ; HPLC-MS: m/z = 548 (M+H) at Rt= 3.6 min. ; IR (KBr): v 1711 (C=O) cm~1.

Example 434 (General procedure XX) 4- (5-Dimethylamino-naphthalene-1-sulfonyl)-piperazine-1-carbox ylic acid 4- (5- trifluoromethyl-pyridin-2-yloxy)-phenyl ester The title compound was prepared from 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl chlorofor- mate and 1- (5-dimethylamino-naphthalene-1-sulfonyl)-piperazine and purified by flash chro- matography (ethyl acetate-heptane 1: 4), yield 32%. Pale crystals, HPLC-MS: m/z: 601 (M+1) at Rt = 5.2 min.; m. p. °C ; IR (KBr): v 1723 (C=O) cm~1.

Example 435 (General procedure 15) 4- (3-Methoxy-benzyl)-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester The hydrochloride of the title compound was prepared from 4- (5-trifluoromethyl-pyridin-2- yloxy)-phenyl chloroformate and 1- (3-methoxy-benzyl)-piperazine, yield 99%. White crystals, m. p. 214-215 °C ; HPLC-MS: m/z: 489 (M+1) at Rt = 2.8 min. ; IR (KBr): v 1712 (C=O) cm~1.

Example 436 (General procedure 15) 4- (3-Fluoro-benzyl)-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester The hydrochloride of the title compound was prepared from 4- (5-trifluoromethyl-pyridin-2- yloxy)-phenyl chloroformate and 1- (3-fluoro-benzyl)-piperazine, yield 77%. White crystals, m. p. 138-139 °C ; HPLC-MS: m/z: 476 (M+1) at Rt = 3.0 min.; IR (KBr): v 1714 (C=O) cm'.

Example 437 (General procedure 18) <BR> <BR> <BR> <BR> 4- (3-Trifluoromethyl-pyridin-2-yi)-piperazine-l-carboxylic acid 4- (5-trifluoromethyl-pyridin-2- yloxy)-phenyl ester The title compound was prepared from 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl chlorofor- mate and 1- (3-trifluoromethyl-pyridin-2-yl)-piperazine, yield 25%. White crystals, m. p. 131- 132 °C ; HPLC-MS: m/z: 513 (M+1) at Rt = 5.0 min.; IR (KBr): v 1722 (C=O) cm~1.

Example 438 (General procedure 15) <BR> <BR> <BR> <BR> 4- (3-Fluorobenzyl)-piperazine-1-carboxylic acid 4- (4, 6-dimethyl-pyrimidin-2-ylsulfanyl)-phenyl ester The hydrochloride of the title compound was prepared from 4- (4, 6-dimethyl-pyrimidin-2- ylsulfanyl)-phenyl chloroformate and 1- (3-fluorobenzyl)-piperazine. The crude product was converted to the free base, yield 48%. White crystals, m. p. 117-118 °C ; HPLC-MS: m/z: 453 (M+1) at Rt = 2.6 min. ; IR (KBr) : v 1714 (C=O) cm~1.

Example 439 (General procedure 15) 5- (4-Trifluoromethoxybenzyl)-2, 5-diazabicyclo [2.2. 1] heptane-2-carboxylic acid 4- (5- trifluoromethylpyridin-2-yloxy)-phenyl ester The hydrochloride of the title compound was prepared from 4- (5-trifluoromethyl-pyridin-2- yloxy)-phenyl chloroformate and 2- (4-trifluoromethoxybenzyl)-2, 5-diazabicyclo [2.2. 1] heptane.

The crude product was converted to the free base, yield 20%. Oil ; HPLC-MS: m/z: 554 (M+1) at Rt = 3.1 min.; IR (KBr): v 1723 (C=O) cm~1.

Example 440 (General procedure 18) 1-Oxo-1'4-thiomorpholine-4-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester The title compound was prepared from 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl chlorofor- mate and thiomorpholine 1-oxide and purified by flash chromatography (ethyl acetate), yield 37%. White crystals, m. p. 156-157 °C ;'H NMR (CDCI3). 8. 47-8.40 (s-like, 1H), 7.94- 7. 87 (dd-like, 1H), 7.24-7. 13 (m, 4H), 7.06-6. 99 (d-like), 4.31-3. 91 (m, 4H), 2.97-2. 87- 2.75 (m, 2H + 2H); IR (KBr): v 1710 (C=O) cm~1.

Example 441 (General procedure 18) 4-(2, 4-Dimethoxyphenyl)-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)- phenyl ester The title compound was prepared from 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl chlorofor- mate and 1-(2, 4-dimethoxyphenyl)-piperazine. Purified by flash chromatography (ethyl ace- tate-heptane 1: 4), yield 69%. White crystals, m. p. 98-99 °C ; HPLC-MS: m/z = 504 (M+1) at

Rt = 4.0 min. ; IR (KBr): v 1733,1712 (C=O) cm'.

Example 442 (General procedure 15) 5-Benzyl-2, 5-diazabicyclo [2.2. 1] heptane-2-carboxylic acid 4- (5-trifluoromethylpyridin-2- yloxy)-phenyl ester The hydrochloride of the title compound was prepared from 4- (5-trifluoromethyl-pyridin-2- yloxy)-phenyl chloroformate and 2-benzyl-2, 5-diazabicyclo [2.2. 1] heptane. The crude product was converted to the free base and further purified by flash chromatography (ethyl acetate- heptane 1: 4), yield 16 %. White crystals, m. p. 114-115 °C ; HPLC-MS: m/z: 470 (M+1) at Rt = 2.6 min.; IR (KBr): v 1718 (C=O) cm~'.

Example 443 (General procedure 10) 4-Aminomethyl-piperidine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester The title compound was prepared from 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl chlorofor- mate and 4-aminomethylpiperidine. The crude product was purified by preparative HPLC (Method C) (32%, off-white crystals). HPLC-MS m/z = 396.1 (M+1), Rt: 2.65 min. purity: 86%.

Example 444 (General procedure 10) 4-Pyrimidin-2-yl-piperazine-1-carboxylic acid 4- (5-chloro-pyridin-2-yloxy)-phenyl ester The title compound was prepared from 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl chlorofor- mate and 1-(2-pyrimidinyl)-piperazine, two equivalent of diisopropylethylamine was added.

The crude product was obtained by filtration of the reaction mixture. The crude product was washed with diethyl ether and subjected to column chromatography, ethyl acetate/heptane (1: 3) (18%, white crystals). HPLC-MS m/z = 412.1 (M+1), Rt: 4.12 min.

Example 445 (General procedure 12) 4-Cyclopropylmethyl-piperazine-1-carboxylic acid 4- (4, 4-dimethyl-2, 6-dioxo-piperidin-1-yl)- phenyl ester The title compound was prepared from 4- (4, 4-dimethyl-2, 6-dioxo-piperidin-1-yl)-phenyl chloroformate and 1-cyclopropylmethyl-piperazine, preparative HPLC (Method C) (45%, off- white crystals). HPLC-MS m/z = 400.3 (M+1), Rt: 1. 83 min.

Example 446 (General procedure 12) 4- (4-Methoxy-benzyl)-piperazine-1-carboxylic acid 4- (4, 4-dimethyl-2, 6-dioxo-piperidin-1-yl)- phenyl ester The title compound was prepared from 4- (4, 4-dimethyl-2, 6-dioxo-piperidin-1-yi)-phenyl chloroformate and 1- (4-methoxybenzyl)-piperazine, preparative HPLC (Method C) (54%, white crystals). HPLC-MS m/z = 466.3 (M+1), Rt: 2.26 min.

Example 447 (General procedure 12) 4-Pyridin-3-ylmethyl-piperazine-1-carboxylic acid 4- (4, 4-dimethyl-2, 6-dioxo-piperidin-1-yl)- phenyl ester The title compound was prepared from 4- (4, 4-dimethyl-2, 6-dioxo-piperidin-1-yl)-phenyl chloroformate and 1-pyridin-3-ylmethyl-piperazine, hydrochloride, preparative HPLC (Method C) (75%, colourless oil). HPLC-MS m/z = 437.2 (M+1), Rt: 1.70 min.

Example 448 (General procedure 12) 4- (4-Methoxy-benzyl)-piperazine-l-carboxylic acid 4- (2-cyclohexyl-acetylamino)-phenyl ester The title compound was prepared from 4- (2-cyclohexyl-acetylamino)-phenyl chloroformate and 1- (4-methoxybenzyl)-piperazine, preparative HPLC (Method C) (49%, white crystals).

HPLC-MS m/z = 466.3 (M+1), Rt: 2.85 min.

Example 449 (General procedure 12) 4-Cyclopropylmethyl-piperazine-1-carboxylic acid 4- (2-cyclohexyl-acetylamino)-phenyl ester The title compound was prepared from 4- (2-cyclohexyl-acetylamino)-phenyl chloroformate and 1-cyclopropylmethyl-piperazine, preparative HPLC (methode C (60%, off-white crystals).

HPLC-MS m/z = 400.3 (M+1), Rt: 2.42 min.

Example 450 (General procedure 12) 4-Pyridin-3-ylmethyl-piperazine-1-carboxylic acid 4- (2-cyclohexyl-acetylamino)-phenyl ester

The title compound was prepared from 4- (2-cyclohexyl-acetylamino)-phenyl chloroformate and 1-pyridin-3-ylmethyl-piperazine, hydrochloride, preparative HPLC (methode C) (64%, white crystals). HPLC-MS m/z = 437.4 (M+1), Rt: 2.38 min.

Example 451 (General procedure 14) Methyl-phenyl-carbamic acid 4- (2-cyclohexyl-ethylsulfamoyl)-phenyl ester The title compound was prepared from N- (2-cyclohexyl-ethyl)-4-hydroxy- benzenesulfonamide and N-methyl-N-phenyl carbamoylchloride, preparative HPLC (Method C) (14%, light yellow oil). HPLC-MS m/z = 417.3 (M+1), Rt: 4.89 min.

Example 452 (General procedure 14) Methyl-phenyl-carbamic acid 4- (3-methyl-butylsulfamoyl)-phenyl ester The title compound was prepared from 4-hydroxy-N- (3-methyl-butyl)-benzenesulfonamide and N-methyl-N-phenyl carbamoylchloride, preparative HPLC (Method C) (11 %, light yellow oil). HPLC-MS m/z = 377.2 (M+1), Rt: 4.32 min.

Example 453 (General procedure 12) (6-Methoxy-pyridin-2-yl)-methyl-carbamic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester The crude product was prepared from 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl chlorofor- mate and and 2-methoxy-6-methylaminopyridine. The reaction mixture was evaporated to dryness, dissolved in dichloromethane (100 ml) and extracted with a aqueous phosphate buffer, pH 7. The aqueous phase was extracted with dichloromethane (100 ml x 2) and the combined organic phases were dryed and evaporated to dryness. The product was sub- jected to flash chromatography, ethyl acetate/heptane (1: 7) to give the titlew product (86%, white crystals). HPLC-MS m/z = 420.4 (M+1), Rt: 5.23 min.

Example 454 (General procedure 12) 4-Benzimidazol-1-yl-piperidine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester The crude product was prepared from 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl chlorofor-

mate and 1-piperidine-4-yl-1 H-benzimidazole, 5 equivalent of diisopropylamine was added, preparative HPLC (method C) (23%, colourless crystals). HPLC-MS m/z = 483.3 (M+1), Rt: 3.14 min.

Example 455 (General procedure 12) 4-Hydroxymethyl-piperidine-1-carboxylic acid 4- (2-cyclohexyl-acetylamino)-phenyl ester The title compound was prepared from 4- (2-cyclohexyl-acetylamino)-phenyl chloroformate and 4-hydroxymethyl-piperidine, praeparative HPLC (Method C) (37%, off-white crystals).

HPLC-MS m/z = 375.2 (M+1), Rt: 3.41 min.

Example 456 (General procedure 12) 4- (4-Amino-phenyl)-piperidine-l-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester The title compound was prepared from 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl chlorofor- mate and 4- (4-aminophenyl) piperidine, hydrochloride, praeparative HPLC (Method C) (30%, light yellow crystals). HPLC-MS m/z = 458.2 (M+1), Rt: 3.42 min.

Example 457 (General procedure 12) 4-(Methyl-pyridin-3-ylmethyl-amino)-piperidine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin- 2-yloxy)-phenyl ester The title compound was prepared from 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl chlorofor- mate and methyl-piperidin-4-yl-pyridin-3-ylmethyl-amine, hydrochloride, præparative HPLC (Method C) (31%, orange oil). HPLC-MS m/z = 487.1 (M+1), Rt: 2.64 min.

Example 458 (General procedure 12) 4- (2-Oxo-pyrrolidin-1-yl)-piperidine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)- phenyl ester The title compound was prepared from 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl chlorofor- mate and 1-piperidin-4-yl-pyrrolidine-2-one, hydrochloride, praeparative HPLC (Method C) (55%, semi-crystaline oil). HPLC-MS m/z = 450.1 (M+1), Rt: 3.81 min.

Example 459 (General procedure 12) 4-(Methyl-phenethyl-amino)-piperidine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)- phenyl ester The title compound was prepared from 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl chlorofor- mate and methyl-phenethyl-piperidin-4-yl-amine, hydrochloride, praeparative HPLC (Method C) (37%, colourless oil). HPLC-MS m/z = 500.1 (M+1), Rt: 3.26 min.

Example 460 4-[(Benzyl-ethyl-amino)-methyl]-piperidine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2- yloxy)-phenyl ester Benzyl-ethyl-piperidin-4-ylmethyl-amine (1.42 mmol) was dissolved in dichloromethane. 4- (5- Trifluoromethyl-pyridin-2-yloxy)-phenyl chloroformate (1.42 mmol, 0.451 g) (prepared from the corresponding phenol by conventional methods) was added at room temperature. The reaction mixture was stirred overnight and evaporated to dryness. The crude product was subjected to column chromatography, ethyl acetate/heptane (1: 3) o Triethylamine/ethyl ace- tate 1: 9). The fractions containing the title product, was evaporated to dryness and HCI (g) in ethyl acetate was added and stirred for 16 hours. The solution was evaporated to dryness and dryed in vacoum for 16 h. to give the title product. (58%, light yellow crystals). HPLC-MS m/z = 514.1 (M+1), Rt: 3.27 min.

Example 461 (General procedure 12) 4-[Methyl-phenethyl-amino)-methyl]-piperidine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin- 2-yloxy)-phenyl ester The title compound was prepared from 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl chlorofor- mate and methyl-phenethyl-piperidin-4-ylmethyl-amine, hydrochloride, 5 equivalent of diiso- propylamine was added, praeparative HPLC (Method C) (46%, colourless crystals). HPLC- MS m/z = 514. 1 (M+1), Rt: 3.31 min.

Example 462 (General procedure 12) 4-[(CycloheXyl-methyl-amino)-methyl]-piperidine-1-carboxylic acid 4- (5-trifluoromethyl- pyridin-2-yloxy)-phenyl ester

The title compound was prepared from 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl chlorofor- mate and cyclohexyl-methyl-piperidine-4-ylmethyl-amine, hydrochloride, 5 equivalent of diisopropylamine was added, praeparative HPLC (Method C) (43%, white crystals). HPLC- MS m/z = 492.3 (M+1), Rt: 3.22 min.

Example 463 (General procedure 12) 4-[(Ethyl-pyridin-4-ylmethyl-amino)-methyl]-piperidine-1-car boxylic acid 4- (5-trifluoromethyl- pyridin-2-yloxy)-phenyl ester The title compound was prepared from 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl chlorofor- mate and ethyl-piperidin-4-ylmethyl-pyridin-4-ylmethyl-amine, hydrochloride, 5 equivalent of diisopropylamine was added, praeparative HPLC (Method C) (25%, off-white crystals).

HPLC-MS m/z = 515.2 (M+1), Rt: 2.77 min.

Example 464 (General procedure 12) 4-[(Benzyl-methyl-amino)-methyl]-piperidine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2- yloxy)-phenyl ester The title compound was prepared from 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl chlorofor- mate and benzyl-methyl-piperidin-4-ylmethyl-amine, hydrochloride, 5 equivalent of diisopro- pylamine was added, praeparative HPLC (Method C) (56%, colourless crystals). HPLC-MS m/z = 500.2 (M+1), Rt: 3.18 min.

Example 465 (General procedure 12) 4-[(Methyl-pyridin-3-ylmethyl-amino)-methyl]-piperidine-1-ca rboxylic acid 4-(5-trifluoromethyl- pyridin-2-yloxy)-phenyl ester The title compound was prepared from 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl chlorofor- mate and methyl-piperidine-4-ylmethyl-pyridine-4-ylmethyl-amine, hydrochloride, 5 equiva- lent of diisopropylamine was added, praeparative HPLC (Method C) (36%, colourless crys- tals). HPLC-MS m/z = 501. 1 (M+1), Rt: 2.74 min.

Example 466 (General procedure 12) 4-(1s3-Dihydro-isoindol-2-ylmethyl)-piperidine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2- yloxy)-phenyl ester

The title compound was prepared from 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl chlorofor- mate and 2-piperidin-4-ylmethyl-2, 3-dihydro-1 H-isoindole, hydrochloride, 5 equivalent of diisopropylamine was added, praeparative HPLC (Method C) (63%, colourless crystals).

HPLC-MS m/z = 498.1 (M+1), Rt: 3.07 min.

Example 467 4-Benzotriazol-1-yl-piperidine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester The title compound was prepared from 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl chlorofor- mate and 1-piperidin-4-yl-1 H-benzotriazole, hydrochloride, 5 equivalent of diisopropylamine was added, praeparative HPLC (Method C) (7%, colourless crystals). HPLC-MS m/z = 506.2 (M+1), Rt: 4.56 min.

Example 468 (General procedure 12) 4-[(Cyclopropylmethyl-amino)-methyl]-piperidine-1-carboxylic acid 4- (5-trifluoromthyl-pyridin- 2-yloxy)-phenyl ester Cyclopropylmethyl-piperidine-4-ylmethyl-amine (0.65 mmol, 110 mg) was dissolve in di- chloromethane. 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl chloroformate (0.65 mmol, 0.208 g) (prepared from the corresponding phenol by conventional methods) was added at-15 °C for 15 min and stired at room temperature overnight and evaporated to dryness. The crude product was purified by preparative HPLC (Method C) (16%, colourless crystals). HPLC-MS m/z = 450.1 (M+1), Rt: 2.98 min.

Example 469 (General procedure 12) 4-[Methyl-(2-pyridin-2-yl-ethyl)-amino]-piperidine-1-carboxy lic acid 4- (5-trifluoromethyl- pyridin-2-yloxy)-phenyl ester The title product was prepared from methyl-piperidin-4-yl- (2-pyridin-2-yl-ethyl)-amine and 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl chloroformate, 5 equivalent of diisopropylamine was added, preparative HPLC (method C) (48%, colourless oil). HPLC-MS m/z = 501.1 (M+1), Rt: 2.77 min.

Example 470 (General procedure 12) 4-(Cyclohexyl-methyl-amino)-piperidine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2- yloxy)-phenyl ester The title product was prepared from cyclohexyl-methyl-piperidin-4-yl-amine, dihydrochloride and 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl chloroformate, 2 equivalent of diisopro- pylamine ; dimethylformamide/tetrahydrofuran (2: 1). The reaction mixture was evaporated to dryness and the crude product extracted with ethyl acetate from an aqueous HCI solution saturated with sodium chloride, pH 1-2. The title product was crystallized from ethyl acetate during evaporation of the solvent, filtered and dryed in vacoum (45%, white crystals). HPLC- MS m/z = 478.2 (M+1), Rt: 3.10 min.

Example 471 (General procedure 12) 4- (Isopropyl-methyl-amino)-piperidine-l-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)- phenyl ester The title product was prepared from isopropyl-methyl-piperidin-4-yl-amine, dihydrochloride and 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl chloroformate ; dimethylformamide as solvent, preparative HPLC (method C) (77%, light yellow oil). HPLC-MS m/z = 438.3 (M+1), Rt: 2.77 min.

Example 472 (General procedure 12) (4-Methoxy-phenyl)-methyl-carbamic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester The title product was prepared from N-methyl-p-anisidine and 4- (5-trifluoromethyl-pyridin-2- yloxy)-phenyl chloroformate, preparative HPLC (method C) (61%, off-white crystals). HPLC- MS m/z = 419.2 (M+1), Rt: 4.67 min.

Example 473 (General procedure 12) (2-Methoxy-phenyl)-methyl-carbamic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester The title product was prepared from 2-methoxy-N-methylamine and 4- (5-trifluoromethyl- pyridin-2-yloxy)-phenyl chloroformate, preparative HPLC (method C) (63%, colourless oil).

HPLC-MS m/z = 419.2 (M+1), Rt: 4.75 min.

Example 474 (General procedure 12) (2-Carbamoyl-4-chloro-phenyl)-methyl-carbamic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)- phenyl ester.

The title product was prepared from 5-chloro-2- (methylamino)-benzamide and 4- (5- trifluoromethyl-pyridin-2-yloxy)-phenyl chloroformate, preparative HPLC (method C) (31%, light yellow oil). HPLC-MS m/z = 466.1 (M+1), Rt: 3.99 min.

Example 475 (General procedure 12) (2-Carbamoyl-phenyl)-methyl-carbamic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester The title product was prepared from 2- (methylamino) benzamide and 4- (5-trifluoromethyl- pyridin-2-yloxy)-phenyl chloroformate, preparative HPLC (method C) (57%, light yellow oil).

HPLC-MS m/z = 454.2 (M+Na), Rt: 3.66 min.

Example 476 (General procedure 12) (2-Chloro-phenyl)-methyl-carbamic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester The title product was prepared from 2-chlor-N-methylaniline and 4- (5-trifluoromethyl-pyridin- 2-yloxy)-phenyl chloroformate, preparative HPLC (method C) (48%, light yellow oil). HPLC- MS m/z = 423.1 (M+1), Rt: 4.98 min.

Example 477 (General procedure 12) (2, 4-Difluoro-phenyl)-methyl-carbamic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester The title product was prepared from 2, 4-difluouro-N-methylaniline and 4- (5-trifluoromethyl- pyridin-2-yloxy)-phenyl chloroformate, preparative HPLC (method C) (37%, white crystals).

HPLC-MS m/z = 425.1 (M+1), Rt: 4.90 min.

Example 478 (General procedure 12) Methyl- (2-trifluoromethoxy-phenyl)-carbamic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester The title product was prepared from N-methyl-2- (trifluoromethoxy)-aniline and 4- (5- trifluoromethyl-pyridin-2-yloxy)-phenyl chloroformate, preparative HPLC (method C) (49%, colourless oil). HPLC-MS m/z = 473.2 (M+1), Rt: 5.18 min.

Example 479 (General procedure 13) Methyl-phenyl-carbamic acid 4- (1, 1,3, 3-tetramethyl-butylcarbamoyl)-phenyl ester The title product was prepared from tert-octylamine and 4- (methyl-phenyl-carbamoyloxy)- benzoic acid 2, 5-dioxo-pyrrolidin-1-yl ester, preparative HPLC (method C) (26%, white crys- tals). HPLC-MS m/z = 383. 5 (M+1), Rt: 4.67 min.

Example 480 (General procedure 13) Methyl-phenyl-carbamic acid 4-[(2-dimethylamino-ethyl)-methyl-carbamoyl]-phenyl ester The title product was prepared from N, N, N'-trimethylethylendiamine and 4- (methyl-phenyl- carbamoyloxy)-benzoic acid 2, 5-dioxo-pyrrolidin-1-yl ester, preparative HPLC (method C) (2%, colourless oill). HPLC-MS m/z = 356.2 (M+1), Rt: 2.17 min.

Example 481 (General procedure 13) Methyl-phenyl-carbamic acid 4- (cyclopropylmethyl-carbamoyl)-phenyl ester The title product was prepared from cyclopropylmethylamine and 4- (methyl-phenyl- carbamoyloxy)-benzoic acid 2, 5-dioxo-pyrrolidin-1-yl ester. The crude product was used without further purification (100%, semi-crystal oil). HPLC-MS m/z = 325.1 (M+1), Rt: 3.40 min.

Example 482 (General procedure 13) Methyl-phenyl-carbamic acid 4- (methyl-pyridin-3-ylmethyl-carbamoyl)-phenyl ester The title product was prepared from methyl-pyridin-3-ylmethyl-amine and 4- (methyl-phenyl- carbamoyloxy)-benzoic acid 2, 5-dioxo-pyrrolidin-1-yl ester. The crude product was subjected to preparative HPLC (method C) (48%, clear colourless oil). HPLC-MS m/z = 376.2 (M+1), Rt: 2.37 min.

Example 483 (General procedure 13) Methyl-phenyl-carbamic acid 4- [ (1 H-benzimidazol-2-ylmethyl)-carbamoyl]-phenyl ester The title product was prepared from C- (l H-benzimidazol-2-yl)-methylamine and 4- (methyl-

phenyl-carbamoyloxy)-benzoic acid 2, 5-dioxo-pyrrolidin-1-yl ester. The crude product was subjected to preparative HPLC (method C) (8%, off-white crystals). HPLC-MS m/z = 401. 1 (M+1), Rt: 2.56 min.

Example 484 (General procedure 13) Methyl-phenyl-carbamic acid 4- [2- (4-chloro-phenyl)-ethylcarbamoyl]-phenyl ester The title product was prepared from 2- (4-chloro-phenyl)-ethylamine and 4- (methyl-phenyl- carbamoyloxy)-benzoic acid 2, 5-dioxo-pyrrolidin-1-yl ester. The crude product was subjected to preparative HPLC (method C) (39%, off-white crystals). HPLC-MS m/z = 409.2 (M+1), Rt: 4.27 min.

Example 485 4-Cyclopropylmethyl-piperazine-1-carboxylic acid 4- (3, 3-dimethyl-butylcarbamoyl)-phenyl ester The title product was prepared from 1-cyclopropylmethylpiperazine (0.35 mmol) dissolved in dichloromethane (5 ml). 4- (3, 3-dimethyl-butylcarbamoyl)-phenyl chloroformate (0.35 mmol) was added at room temperature. The reaction mixture was stirred for 16 h and evaporated to dryness and subjected to preparative HPLC (metod C) (5%, white crystals). HPLC-MS m/z = 388.2 (M+1), Rt: 2.43 min.

Example 486 4-Hydroxymethyl-piperidine-1-carboxylic acid 4- (3, 3-dimethyl-butylcarbamoyl)-phenyl ester ester The title product was prepared from 4-hydroxymethylpiperidine (0.35 mmol) was dissolved in dichloromethane (5 ml). Diisopropylethylamine (0.35 mmol was added together with 4- (3, 3- dimethyl-butylcarbamoyl)-phenyl chloroformate (0.35 mmol) at room temperature. The reac- tion mixture was stirred for 16 h and evaporated to dryness and subjected to preparative HPLC (metod C). (25%, white crystals). HPLC-MS m/z = 363.3 (M+1), Rt: 3.27 min.

Example 487 4-Pyridin-3-ylmethyl-piperazine-1-carboxylic acid 4- (3, 3-dimethyl-butylcarbamoyl)-phenyl es- ter

The title product was prepared from 1-pyridin-3-ylmethyl-piperazine was dissolved in di- chloromethane (5 ml). 4- (3, 3-Dimethyl-butylcarbamoyl)-phenyl chloroformate (0.35 mmol) was added at room temperature. The reaction mixture was stirred for 16 h and evaporated to dryness and subjected to preparative HPLC (metod C) (88%, light yellow oil). HPLC-MS m/z = 425.4 (M+1), Rt: 2.33 min.

Example 488 4- (4-Methoxy-benzyl)-piperazine-1-carboxylic acid 4- (3, 3-dimethyl-butylcarbamoyl)-phenyl ester The title product was prepared from 1- (4-methoxy-benzyl)-piperazine (0.35 mmol) was dis- solved in dichloromethane (5 ml). 4- (3, 3-Dimethyl-butylcarbamoyl)-phenyl chloroformate (0.35 mmol) was added at room temperature. The reaction mixture was stirred for 16 h and evaporated to dryness and subjected to preparative HPLC (metod C). (54%, colourless semi- crystaline oil). HPLC-MS m/z = 454.3 (M+1), Rt: 2.78 min.

Example 489 4-(2-Pyridin-2-yl-acetyl)-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester a) Piperazine-1, 4-dicarboxylic acid tert-butyl ester 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester (General procedure 18) The title compound was prepared from 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl chlorofor- mate and 1-tert-butoxycarbonyl-piperazin, yield 59% (recrystallized from EtOAc-heptane 1: 1).

White crystals, m. p. 165-166 °C ;'H NMR (CDC13) a 8.45-8. 42 (m, 1H), 7.92-7. 87 (m, dd- like, 1 H), 7.21-7. 12 (AB-system, 4H), 7.03-6. 98 (m, d-like, 1 H), 3.72-3. 45 (br m, 8H), 1.49 (s, 9H) ;'3C-NMR (CDCI3) 0 (ref. Cd1377. 00 ppm): 165.71, 154.56, 153.51, 150.21, 148.34, 145.43 (q, J= 4.4 Hz), 136.701 (q, J = 3 Hz), 123.65 (q, J= 271.5 Hz), 122. 86, 122. 24,121. 62 (q, J = 33 Hz), 11.20, 80. 32,44. 38,43. 78,44. 6-42.3 (br), 28.36 ppm ; R (KBr) Q 1722 (C=O), 1691 (C=O) cm-1. b) Piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester hydrochloride Piperazine-1, 4-dicarboxylic acid ter-butyl ester 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester

(0.12 g, 0.26 mmol) was stirred at 100 °C for 10 min in a mixture of ethanol (3 ml) and concen- trated hydrochloric acid (1 ml). The solvent was removed in vacuum. The residue was stirred with toluene (10 ml) and evaporated, then stirred with ethanol and evaporated to dryness to give white crystals (0.10 g). Recrystallization from absolute ethanol gave the title compound. White <BR> <BR> <BR> crystals, 0.068 g (65%); m. p. 279-282 °C (decomp. ) ;'H-NMR (DMSO) Q 9.62 (br, 2H, NH2+), 8.61-8. 55 (m, 1 H), 8.29-8. 21 (m, dd-like, 1 H), 7.30-7. 20 (m, 5H), 3.86 and 3.70 (br s, 4H), 3.19 (brs, 4H) ; 13C-NMR (DMSO) D (ref DMSO 39.50 ppm): 165.51, 152.71, 149.98, 148. 04, 145.20 (J = 4.4 Hz), 137.62 (J = 3.7 Hz), 123.87 (J = 271.5 Hz), 123.11, 123.39, 120.39 (J = 32.2Hz), 111.80, 42.15 and a broad signal partly overlapping with the DMSO signal. IR (KBr) a 1731,1709 (C=O) cm'. c) 4-(2-Pyridin-2-yl-acetyl)-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)- phenyl ester Triethylamine (0.026 ml) was added to a stirred solution of (pyridin-2-yl) acetic acid hydrochlo- ride (0.033 g, 0.19 mmol) in DMF (2.5 mi) at 0 °C. 1-Hydroxy-benzotriazole containing 8% of water (0.034 g) and then 1- (3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.044 g) was added and the mixture was stirred for 50 min. Piperazine-1-carboxylic acid 4- (5- trifluoromethyl-pyridin-2-yloxy)-phenyl ester hydrochloride (0.070 g) in a mixture of DMF (1 mi) and triethylamine (0.032 mi) was added and stirring was continued over night at room tempera- ture. The solvent was removed in vacuum and the residue was partitioned between dichloro- methane (10 mi) and water (10 ml). The organic phase was washed with water (10 ml), dried over sodium sulfate, filtered and evaporated. The residue was triturated with ether- petroleumsether 1: 1 and the (2 + 1 ml). The residue was dried to give the title compound. White solid, m. p. 143-146 °C ; HPLC-MS m/z : IR (KBr) D 1732 (C=O), 1643 (C=O).

Example 490 (General procedure 15) <BR> <BR> <BR> 4- (2-Pyridin-4-yl-ethyl)-piperazine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl ester The hydrochloride of the title compound was prepared from 4- (5-trifluoromethyl-pyridin-2-yloxy)- phenyl chloroformate and 1- (4-pyridin-2-yi-ethyl)-piperazine. White crystals, m. p. 268-271 °C (decomp); IR (KBr) a 2680,2579, 2456 (N+-H), 1731,1713 (C=O) cm-1 ; HPLC-MS m/z: 473 (M+H) Rt = 2.3 min.

Example 491 Methyl-phenyl-carbamic acid 5-amino-pyridin-2-yl ester A solution of methyl-phenyl-carbamic acid 5-nitro-pyridin-2-yl ester (10.41 g, 38.1 mmol) in tet- rahydrofuran (100 mL) was hydrogenated in a Parr apparatus with wet 5% palladium on carbon and 20 psi hydrogen pressure. After 2 hours the solution was filtered over a short pad of Celite, washed thoroughly with ethyl acetate and evaporated in vacuo, yielding title compound (9.51 g, 103% yield) as a thick oil, which solidified upon standing.

1H NMR (300MHz, CDCI3) : 8 = 3.40 (br. s, 3H), 3.70 (br. s, 2H), 6. 80 (br. d, 1H), 6.97 (dd, 1H), 7.22 (m, 1 H), 7.36 (m, 4H), 7.72 (d, 1 H) ; HPLC-MS (Method A): m/z = 244 (M+H) + ; Rt = 2.28 min.

Example 492 Methyl-phenyl-carbamic acid 5-benzenesulfonylamino-pyridin-2-yl ester Benzenesulphonyl chloride (0.18 g, 1.00 mmol), dissolved in a small amount of dichloro- methane, was added dropwise to a stirred solution of methyl-phenyl-carbamic acid 5-amino- pyridin-2-yl ester (0.24 g, 1.00 mmol) and triethylamine (0.10 g, 1.00 mmol) in dichloromethane (10 mL). After stirring for 4 hours the solution was extracted with water and evaporated in vacuo. The residue was purified by flash column chromatography (Si02, ethyl acetate: heptane 40: 60 followed by 50: 50) yielding the title compound (108 mg, 23% yield) as a white solid.

'H NMR (300MHz, CDCI3) : S = 3.46 (br. s, 3H), 6.82 (br. s, 1 H), 7.24-7. 52 (m, 9H), 7.63 (m, 3H), 7. 84 (br. s, 1 H) ; HPLC-MS (Method A): m/z = 384 (M+H) + ; Rt = 3.26 min.

Example 493 3, 3-Dimethyl-4- [6- (methyl-phenyl-carbamoyloxy)-pyridin-3-ylcarbamoyl]-butyric acid A solution of methyl-phenyl-carbamic acid 5-amino-pyridin-2-yl ester (243 mg, 1.00 mmol) and 3, 3-dimethylglutaric anhydride (142 mg, 1.00 mmol) in dichloromethane (10 mL) was stirred at room temperature for 48 hours. Evaporation of the solvent yielded the title compound as a thick oil.

HPLC-MS (Method A): m/z = 386 (M+H) + ; Rt = 2.76 min.

Example 494 Piperidine-1-carboxylic acid 4, 4-dimethyl-2, 6-oxo-3, 4,5, 6-tetrahydro-2H- [1, 3'] bipyridinyl-6'-yl

1-Piperidinecarbonyl chloride (63 microL, 0.50 mmol) was added to a solution of 6'-hydroxy-4, 4- dimethyl4, 5-dihydro-3H- [1, 3 bipyridinyl-2, 6-dione (117 mg, 0.50 mmol) and DABCO (56 mg, 0.50 mmol) in dimethylformamide (10 mL). After stirring for 1 hour at room temperature water was added and the solution was extracted twice with dichloromethane. The combined organic layers were dried over sodium sulphate, filtered and evaporated in vacuo. The residue was crys- tallied from ethyl acetate: heptane yielding the title compound (0.12 g, 69% yield) as a white solid.

'H NMR (300MHz, CDCI3) : 8 = 1.21 (s, 6H), 1.64 (s, 6H), 2.69 (s, 4H), 3.53 (m, 2H), 3.63 (m, 2H), 7.22 (d, 1 H), 7.49 (dd, 1 H), 8.09 (d, 1 H) ; HPLC-MS (Method A): m/z = 346 (M+H) ; Rt = 3.12 min.

Example 495 2, 2-Dimethyl-N-[6-(methyl-phenyl-carbamoyloxy)-pyridin-3-yl]-s uccinamic acid A solution of methyl-phenyl-carbamic acid 5-amino-pyridin-2-yl ester (0.49 g, 2.00 mmol) and 2, 2-dimethylsuccinic anhydride (0.26 g, 2.00 mmol) in dichloromethane (10 mL) was stirred at room temperature overnight. Evaporation of the solvent in vacuo yielded the title compound.

HPLC-MS (Method A): m/z = 372 (M+H) + ; Rt = 2.84 min.

Example 496 Methyl-phenyl-carbamic acid 5- (3, 3-dimethyl-2, 5-dioxo-pyrrolidin-1-yl)-pyridin-2-yl ester A mixture of thionyl chloride (0.726 mL, 10.00 mmol) and 2, 2-dimethyl-N- [6- (methyl-phenyl- carbamoyloxy)-pyridin-3-yl]-succinamic acid (0.74 g, 2.00 mmol) in dichloromethane (25 mL) was stirred at room temperature for 18 hours. The solvent and excess thionyl chloride were evaporated in vacuo. The crude product was redissolved in dichloromethane (25 mL) and pyri- dine (316 mg, 4.00 mmol) was added. The solution was extracted with water, dried over sodium sulphate, filtered and evaporated in vacuo. The residue was purified by flash column chroma- tography (Si02, ethyl acetate: heptane 50: 50), yielding the title compound (490 mg, 69% yield) as a white solid.

'H NMR (300MHz, CDCI3) : 6 = 1.43 (s, 6H), 2.74 (s, 2H), 3.45 (br. s, 3H), 7.14 (br. s, 1H), 7.26 (m, 1 H), 7.38 (m, 4H), 7.76 (br. d, 1 H), 8.39 (s, 1 H) ; HPLC-MS (Method A): m/z = 354 (M+H) + ; Rt = 3.35 min.

Example 497 Methyl-phenyl-carbamic acid 5- [3, 3-dimethyl-5- (4-methyl-piperazin-1-yl)-5-oxo-pentanoylamino]- pyridin-2-yl ester Thionyl chloride (56 microL, 0.78 mmol) was added to a stirred solution of 3, 3-dimethyl-4- [6- (methyl-phenyl-carbamoyloxy)-pyridin-3-ylcarbamoyl]-butyric acid (0. 15 g, 0.39 mmol) in di- chloromethane (5 mL) and 2 drops of formamide. After stirring for 10 minutes N- methylpiperazine (1 mL) was added and stirring was continued for 2 hours. The solvent was evaporated in vacuo. The residue was redissolved in dichloromethane and extracted with water, dried over sodium sulphate, filtered and evaporated in vacuo. The crude product was purified by filtration over a short column (Si02, ethyl acetate followed by acetone) yielding the title com- pound (93 mg, 51 % yield) as a thick oil.

1H NMR (300MHz, Cd13) : 8 = 1. 11 (s, 6H), 2.32 (s, 3H), 2.43 (m, 8H), 3.42 (br. s, 3H), 3.61 (m, 2H), 3.74 (m, 2H), 7.00 (br. s, 1H), 7.38 (d, 4H), 8.21 (dd, 1H), 8.47 (d, 1H), 10.90 (s, 1H) ; HPLC-MS (Method A): m/z = 468 (M+H) + ; Rt = 2.20 min.

Example 498 Methyl-phenyl-carbamic acid 5- [3, 3-dimethyl-4- (pyridin-3-ylcarbamoyl)-butyrylamino]-pyridin-2-yl ester Thionylchloride (237 microL, 3.27 mmol) was added to a stirred solution of 3, 3-dimethyl-4-[6- (methyl-phenyl-carbamoyloxy)-pyridin-3-ylcarbamoyl]-butyric acid (0.63 g, 1.63 mmol) in di- chloromethane (10 mL). After stirring for 10 minutes the solution was divided into 4 equal por- tions of acid chloride. To one portion was added 2-aminopyridine (0.5 mL) and after stirring for 2 hours at room temperature the crude product was purified by flash column chromatography (SiO2, ethyl acetate followed by ethyl acetate: acetone 90: 10), yielding the title compound (105 mg, 56% yield).

'H NMR (300MHz, CDCI3) : 8 = 1.09 (s, 6H), 2.36 (s, 2H), 2.38 (s, 2H), 3.44 (br. s, 3H), 6.95 (br. s, 1H), 7.26 (m, 2H), 7.38 (m, 4H), 8.05 (dd, 1H), 8.10 (dt, 1H), 8.30 (m, 2H), 8.67 (d, 1H) ; HPLC-MS (Method A): m/z = 462 (M+H) + ; Rt = 2.52 min.

Example 499 Methyl-phenyl-carbamic acid 5- (3, 3-dimethyl-5-morpholin-4-yl-5-oxo-pentanoylamino)-pyridin-2- yl ester

Thionylchloride (237 microL, 3.27 mmol) was added to a stirred solution of 3, 3-dimethyl-4- [6- (methyl-phenyl-carbamoyloxy)-pyridin-3-ylcarbamoyl]-butyric acid (0.63 g, 1.63 mmol) in di- chloromethane (10 mL). After stirring for 10 minutes the solution was divided into 4 equal por- tions of acid chloride. To one portion was added morpholine (0.5 mL) and after stirring for 2 hours at room temperature the crude product was purified by flash column chromatography (Si02), yielding the title compound (117 mg, 63% yield).

'H NMR (300MHz, CDCI3) : 8 = 1. 11 (s, 6H), 2.44 (s, 4H), 3.42 (br. s, 3H), 3.59 (m, 2H), 3.70 (m, 6H), 7.00 (br. s, 1H), 7.24 (m, 1H), 7. 38 (d, 4H), 8.21 (dd, 1H), 8.45 (d, 1H), 10.76 (s, 1H) ; HPLC-MS (Method A): m/z = 455 (M+H) + ; Rt = 2.87 min.

Example 500 Methyl-phenyl-carbamic acid 5- [4- (2-dimethylamino-ethylcarbamoyl)-3, 3-dimethyl- butyrylamino]-pyridin-2-yl ester Thionylchloride (237 microL, 3.27 mmol) was added to a stirred solution of 3, 3-dimethyl-4- [6- (methyl-phenyl-carbamoyloxy)-pyridin-3-ylcarbamoyl]-butyric acid (0.63 g, 1.63 mmol) in di- chloromethane (10 mL). After stirring for 10 minutes the solution was divided into 4 equal por- tions of acid chloride. To one portion was added N, N-dimethylethylenediamine (0.5 mL) and af- ter stirring for 2 hours at room temperature the crude product was purified by flash column chromatography (Si02), yielding the title compound (74 mg, 39% yield).

'H NMR (300MHz, CDCI3) : 8 = 1.10 (s, 6H), 2.22 (s, 2H), 2.27 (s, 6H), 2.44 (m, 4H), 3.37 (m, 2H), 3.43 (br. s, 3H), 6.60 (br. t, 1 H), 7.00 (br. s, 1H), 7.25 (m, 1H), 7.38 (d, 4H), 8.21 (dd, 1 H), 8.46 (d, 1 H), 10.70 (s, 1 H) ; HPLC-MS (Method A): m/z = 456 (M+H) + ; Rt = 1. 93 min.

Example 501 (General procedure 12) 4-[Methyl-(2-pyridin-4-yl-ethyl)-amino]-piperidine-1-carboxy lic acid 4- (5-trifluoromethyl- pyridin-2-yloxy)-phenyl ester The title product was prepared from methyl-piperidine-4-yl- (2-pyridin-4-yl-ethyl)-amine and 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl chloroformate, 3 equivalent of diisopropylamine was added, preparative HPLC (method C) (15%, colourless oil). HPLC-MS m/z = 501.4 (M+1), Rt: 2.04 min.

Example 502 (General procedure 12) 4-(Cyclopropyl-pyridin-4-ylmethyl-amino)-piperidine-1-carbox ylic acid 4- (5-trifluoromethyl-

pyridin-2-yloxy)-phenyl ester The title product was prepared from cyclopropyl-piperidine-4-yl-pyridin-4-ylmethyl-amine and 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl chloroformate, 3 equivalent of diisopropylamine was added, solvent : dimethylformamide. The crude reaction mixture was evaporated without addition of acetic acid, preparative HPLC (method C) (19%, yellow oil). HPLC-MS m/z = (M+1), Rt: 2. 82 min.

Example 503 (General procedure 12) 4-[Cyclopropyl-(2-fluoro-benzyl)-amino]-piperidine-1-carboxy lic acid 4- (5-trifluoromethyl- pyridin-2-yloxy)-phenyl ester The title product was prepared from cyclopropyl-(2-fluoro-benzyl)-piperidin-4-yl-amine and 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl chloroformate, 3 equivalent of diisopropylamine was added, solvent: dimethylformamide. The crude reaction mixture was evaporated without ad- dition of acetic acid, preparative HPLC (method C) (60%, colourless oil). HPLC-MS m/z = (M+1), Rt: 3. 02 min.

Example 504 (General procedure 12) 4-(Cyclopropyl-pyridin-3-ylmethyl-amino)-piperidine-1-carbox ylic acid 4- (5-trifluoromethyl- pyridin-2-yloxy)-phenyl ester The title product was prepared from cyclopropyl-piperidin-4-yl-pyridin-3-ylmethyl-amine and 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl chloroformate, 3 equivalent of diisopropylamine was added, solvent: dimethylformamide. The crude reaction mixture was evaporated without addition of acetic acid, preparative HPLC (method C) (26%, light brown solid). HPLC-MS m/z = (M+1) 513.3, Rt: 2. 64 min.

Example 505 (General procedure 12) 4-(Cyclopropylmethyl-pyridin-3-ylmethyl-amino)-piperidine-1- carboxylic acid 4- (5- trifluoromethyl-pyridin-2-yloxy)-phenyl ester The title product was prepared from cyclopropylmethyl-piperidin-4-yl-pyridin-3-ylmethyl- amine and 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl chloroformate, 3 equivalent of diiso- propylamine was added, solvent: dimethylformamide. The crude reaction mixture was evapo- rated without addition of acetic acid, preparative HPLC (method C) (47%, off-white solid.

HPLC-MS m/z = (M+1) 513.3, Rt: 2.70 min.

Example 506 (General procedure 12) 4-(Cyclopropylmethyl-pyridin-3-ylmethyl-amino)-piperidine-1- carboxylic acid 4- (5- trifluoromethyl-pyridin-2-yloxy)-phenyl ester The title product was prepared from cyclopropylmethyl-piperidin-4-yl-pyridin-4-ylmethyl- amine and 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl chloroformate, 3 equivalent of diiso- propylamine was added, solvent : dimethylformamide. The crude reaction mixture was evapo- rated without addition of acetic acid, preparative HPLC (method C) (22%, off-white solid.

HPLC-MS m/z = (M+1) 513.3, Rt: 2.70 min.

Example 507 (General procedure 12) 4- (4-Hydroxy-piperidin-1-ylmethyl)-piperidine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2- yloxy)-phenyl ester The title product was prepared from 1-piperidin-4-ylmethyl-piperidine-4-ol (released form the correspondent hydrochloride by a standard procedure) and 4- (5-trifluoromethyl-pyridin-2- yloxy)-phenyl chloroformate, preparative HPLC (method C) (reaction performed in a mixture of dichloromethane and dimethylformamide). 1.7 M HCI in ethyl acetate was added to the pooled fractions containing the title product, and the fractions was evaporated to dryness (92%, white solid. HPLC-MS m/z = (M+1) 480. 4, Rt: 2.38 min.

Example 508 (General procedure 11) 4- {3- [1- (2-Hydroxy-ethyl)-piperidin-4-yl]-propyl}-piperidine-1-carbo xylic acid 4- (5- trifluoromethyl-pyridin-2-yloxy)-phenyl ester The title product was prepared from 2- [4- (3-piperidin-4-yl-propyl)-piperidin-1-yl]-ethanol and 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl chloroformate. The reaction mixture was evapo- rated, diethyl ether (30 ml) was added and the title product isolated by filtration, washed with diethyl ether and ried to give (67%, white solid. HPLC-MS m/z = (M+1) 536.2, Rt: 3.39 min.

Example 509 (General procedure 12) 4-(2-Pyrrolidin-1-yl-ethyl)-piperidine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin-2-yloxy)- phenyl ester

The title product was prepared from 2- [4- (3-piperidin-4-yl-propyl)-piperidin-1-yl]-ethanol and 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl chloroformate, preparative HPLC (method C). 1.7 M HCI in ethyl acetate was added to the pooled fractions containing the title product, and the fractions was evaporated to dryness (65%, white solid). HPLC-MS m/z = (M+1) 464.1, Rt: 2.99 min.

Example 510 (General procedure 16) Methyl-o-tolyl-carbamic acid 4-iodo-pyrazol-1-yl ester The title compound was prepared from 1-hydroxy-4-iodopyrazole and methyl-o-tolylamine.

The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (40%, oil).

HPLC-MS: m/z = 380.1 (M+23); Rt = 4.05 min.

Example 511 (General procedure 16) Methyl-m-tolyl-carbamic acid 4-iodo-pyrazol-1-yl ester The title compound was prepared from 1-hydroxy-4-iodopyrazole and methyl-m-tolylamine.

The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (44%, oil).

HPLC-MS: m/z = 380.1 (M+23); Rt = 4.13 min.

Example 512 (General procedure 16) Methyl-p-tolyl-carbamic acid 4-iodo-pyrazol-1-yl ester The title compound was prepared from 1-hydroxy-4-iodopyrazole and methyl-p-tolylamine.

The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (55%, oil).

HPLC-MS : m/z= 380.1 (M+23); Rt = 4.13 min.

Example 513 (General procedure 16) (3-Chloro-phenyl)-methyl-carbamic acid 4-iodo-pyrazol-1-yl ester The title compound was prepared from 1-hydroxy-4-iodopyrazole and 3-chlorophenyl- methylamine. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (54%, oil).

HPLC-MS: m/z = 399.9 (M+23); Rt = 4.28 min.

Example 514 (General procedure 16) (3-Fluoro-phenyl)-methyl-carbamic acid 4-iodo-pyrazol-1-yl ester The title compound was prepared from 1-hydroxy-4-iodopyrazole and 3-fluorophenyl- methylamine. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (51 %, oil).

HPLC-MS: m/z = 384.0 (M+23); Rt = 4.00 min.

Example 515 (General procedure 16) 4- (3-Trifluoromethyl-pyridin-2-yl)-piperazine-1-carboxylic acid 4-iodo-pyrazol-1-yl ester The title compound was prepared from 1-hydroxy-4-iodopyrazole and 1- (3- trifluoromethylpyridin-2-yl) piperazine. The crude product was purified by flash chromatogra- phy (Quad flash 12, EtOAc-heptane) (13%, oil).

HPLC-MS: m/z = 468.1 (M+1); Rt = 4.38 min.

Example 516 (General procedure 16) 2, 6-Dimethyl-morpholine-4-carboxylic acid 4-iodo-pyrazol-1-yl ester The title compound was prepared from 1-hydroxy-4-iodopyrazole and 2, 6-dimethylmorpholin.

The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (11 %, oil).

HPLC-MS : m/z = 374.0 (M+23); Rt = 3.24 min.

Example 517 (General procedure 16) Thiomorpholine-4-carboxylic acid 4-iodo-pyrazol-1-yl ester The title compound was prepared from 1-hydroxy-4-iodopyrazole and thiomorpholin. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (27%, oil).

HPLC-MS: m/z = 340.0 (M+1); Rt = 3.22 min.

Example 518 (General procedure 16) 3, 5-Dimethyl-morpholine-4-carboxylic acid 4-iodo-pyrazol-1-yl ester

The title compound was prepared from 1-hydroxy-4-iodopyrazole and 3, 5-dimethylmorpholin.

The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (15%, oil).

HPLC-MS: m/z= 352.0 (M+1); Rt = 3.17 min.

Example 519 (General procedure 16) Piperidine-1-carboxylic acid 4-iodo-pyrazol-1-yl ester The title compound was prepared from 1-hydroxy-4-iodopyrazole and piperidine. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (46%, oil).

HPLC-MS: m/z = 322.0 (M+1); Rt = 3.38 min.

Example 520 (General procedure 16) Methyl-o-tolyl-carbamic acid 2-chloro-imidazol-1-yl ester The title compound was prepared from 1-hydroxy-2-chloroimidazole, hydrochloride and methyl-o-tolylamine. The crude product was purified by preparative HPLC (Gilson) (4%, red oil).

HPLC-MS: m/z = 266.0 (M); Rt = 3.28 min.

Example 521 (General procedure 16) (3-Fluoro-phenyl)-methyl-carbamic acid 2-chloro-imidazol-1-yl ester The title compound was prepared from 1-hydroxy-2-chloroimidazole, hydrochloride and 3- fluorophenyl-methylamine. The crude product was purified by preparative HPLC (Gilson) (2%, oil).

HPLC-MS: m/z = 270.1 (M); Rt = 3.08 min.

Example 522 Methyl-phenyl-carbamic acid 4-iodo-phenyl ester To a solution of 4-iodophenol (30 mmol) in CH2CI2 (100 mL) was added N-methyl-N- phenylcarbamoyl chloride (27 mmol) and diisopropylethylamine (60 mmol) at room tempera- ture. The reaction mixture was stirred for 16 hours at rt, added CH2CI2 (20 mL) and washed with aqueous citric acid (5%), aqueous Na2CO3 and brine. The organic phase was dried

(MgS04) and evaporated to give the crude product which was purified by FC (Quad flash 40 EtOAc-Heptane) to give 6.55 g (69%) of the title compound as light brown crystals.

'H NMR (300MHz ; CDCI3) : s 3.38 (br s, 3H), 6. 88 (d, 2H), 7.22-7. 46 (m, 5H), 7.62 (d, 2H); HPLC-MS: m/z = 354.0 (M+1); Rt = 4.54 min.

Example 523 (General procedure 20) Methyl-phenyl-carbamic acid 4'-trifluoromethyl-biphenyl-4-yl ester The title compound was prepared from methyl-phenyl-carbamic acid 4-iodo-phenyl ester and 4-trifluoromethylphenylboronic acid. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane 1: 9) (42%, light brown crystals).

HPLC-MS: m/z= 372.1 (M+1); Rt = 5.19 min.

Example 524 (General procedure 20) Methyl-phenyl-carbamic acid 4'-trifluoromethoxy-biphenyl-4-yl ester The title compound was prepared from methyl-phenyl-carbamic acid 4-iodo-phenyl ester and 4-trifluoromethoxyphenylboronic acid. The crude product was purified by flash chromatogra- phy (Quad flash 12, EtOAc-heptane 1: 9) (17%, brown oil).

HPLC-MS: m/z = 388.1 (M+1) ; Rt = 5.27 min.

Example 525 (General procedure 20) Methyl-phenyl-carbamic acid 4-pyridin-3-yl-phenyl ester The title compound was prepared from methyl-phenyl-carbamic acid 4-iodo-phenyl ester and pyridine-3-boronic acid. The crude product was purified by preparative HPLC (Gilson) (5%, brown oil).

'H NMR (300MHz ; CDCI3) : 8 3.46 (brs, 3H), 7.29-7. 46 (m, 7H), 7.61 (d, 2H), 7.88 (dd, 1H), 8.41 (d, 1H), 8.78 (d, 1 H) ; HPLC-MS: m/z = 305.1 (M+1); Rt = 2.99 min.

Example 526 (General procedure 20) Methyl-phenyl-carbamic acid 4- (5-chloro-thiophen-2-yl)-phenyl ester The title compound was prepared from methyl-phenyl-carbamic acid 4-iodo-phenyl ester and 5-chloro-2-thiopheneboronic acid. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane 1: 9) (53%, pink crystals).

1H NMR (300MHz ; CDCI3) : a 3.43 (br s, 3H), 6.87/d, 1 H), 7.00 (d, 1 H), 7.13 (br d, 2H), 7.26- 7.48 (m, 7H); HPLC-MS: m/z= 344.0 (M+1); Rt = 5.16 min.

Example 527 (General procedure 20) Methyl-phenyl-carbamic acid 4'-benzylsulfamoyl-biphenyl-4-yi ester The title compound was prepared from methyl-phenyl-carbamic acid 4-iodo-phenyl ester and 4-benzylsulfamoylbenzeneboronic acid. The crude product was purified by preparative HPLC (Gilson) (35%, pink crystals).

HPLC-MS : m/z = 473.0 (M+1); Rt = 4.80 min.

Example 528 Methyl-phenyl-carbamic acid 4-styryl-phenyl ester Styrene (1.2 mmol), N-methyldicyclohexylamine (1.2 mmol), Pd2 (dba) 3 (0. 03 mmol), Pd (P (t- Bu) 3) 2 (0.06 mmol) and methyl-phenyl-carbamic acid 4-iodo-phenyl ester (1.0 mmol) were added to a Schlenk tube under nitrogen. The Schlenk tube was evacuated and refilled with nitrogen five times. Then dioxane (2 mL) was added and the reaction mixture was stirred at 70 °C for 8 h. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) giving the title compound in 17% yield as colorless crystals.

HPLC-MS: m/z = 330.1 (M+1); Rt = 5.08 min.

Example 529 Methyl-phenyl-carbamic acid 4-phenylethynyl-phenyl ester Phenylacetylene (1.2 mmol), diisopropylamine (1.2 mmol), Cul (0.03 mmol), Pd2 (dba) 3 (0.03 mmol), Pd (P (t-Bu) 3) 2 (0.06 mmol) and methyl-phenyl-carbamic acid 4-iodo-phenyl ester (1.0 mmol) were added to a Schlenk tube under nitrogen. The Schlenk tube was evacuated and refilled with nitrogen five times. Then dioxane (2 mL) was added and the reaction mixture was stirred at 70 °C for 8 h. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) giving the title compound in 41 % yield as brown oil.

HPLC-MS: m/z = 328.1 (M+1); Rt = 5.07 min.

Example 530 3- [4- (Methyl-phenyl-carbamoyloxy)-phenyl]-acrylic acid methyl ester

Methylacrylate (1.2 mmol), N-methyldicyclohexylamine (1.2 mmol), Pd2 (dba) 3 (0.03 mmol), Pd (P (t-Bu) 3) 2 (0.06 mmol) and methyl-phenyl-carbamic acid 4-iodo-phenyl ester (1.0 mmol) were added to a Schlenk tube under nitrogen. The Schlenk tube was evacuated and refilled with nitrogen five times. Then dioxane (2 mL) was added and the reaction mixture was stirred at 70 °C for 8 h. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) giving the title compound in 70% yield as a yellow solid.

HPLC-MS: m/z = 312.1 (M+1); Rt = 4.19 min.

Example 531 (General procedure 8) Methyl-phenyl-carbamic acid 5-phenylsulfanyl-pyrazol-1-yl ester The title compound was prepared from 1-hydroxy-5-phenylsulfanylpyrazole and N-methyl-N- phenylcarbamoyl chloride. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (80%, oil).

'H NMR (300MHz ; CDCI3) : a 3.36 (br s, 3H), 6.47 (d, 1H) 7.16-7. 32 (m, 10H), 7.40 (d, 1H) ; HPLC-MS: m/z = 326.0 (M+1); Rt = 4.42 min.

Example 532 (General procedure 21) Methyl-phenyl-carbamic acid 4- (toluene-4-sulfonylamino)-phenyl ester The title compound was prepared in 8% yield as a clear oil using toluenesulfonyl chloride as the aryl sulfonyl chloride.

HPLC-MS: m/z= 397.1 (M+1); Rt = 4.13 min Example 533 (General procedure 21) Methyl-phenyl-carbamic acid 4- (5-pyridin-2-yl-thiophene-2-sulfonylamino)-phenyl ester The title compound was prepared in 7% yield as an oil using 5-pyridin-2-yl-thiophene-2- sulfonyl chloride as the aryl sulfonyl chloride.

HPLC-MS: m/z = 466.1 (M+1); Rt = 4.23 min.

Example 534 (General procedure 21) Methyl-phenyl-carbamic acid 4- (1-methyl-1 H-imidazole-4-sulfonylamino)-phenyl ester The title compound was prepared in 21% yield as crystals using 1-methyl-1 H-imidazole-4- sulfonyl chloride as the aryl sulfonyl chloride.

HPLC-MS: m/z = 387.1 (M+1); Rt = 3.14 min.

Example 535 (General procedure 21) Methyl-phenyl-carbamic acid 4- (2, 5-dichloro-thiophene-3-sulfonylamino)-phenyl ester The title compound was prepared in 2% yield as an oil using 2, 5-dichloro-thiophene-3- sulfonyl chloride as the aryl sulfonyl chloride.

HPLC-MS: m/z = 458.6 (M+1); Rt = 4.38 min.

Example 536 (General procedure 21) Methyl-phenyl-carbamic acid 4- (5-chloro-1, 3-dimethyl-1 H-pyrazole-4-sulfonylamino)-phenyl ester The title compound was prepared in 3% yield as an oil using 5-chloro-1, 3-dimethyl-1 H- pyrazole-4-sulfonyl chloride as the aryl sulfonyl chloride.

HPLC-MS: m/z = 435.1 (M+1); Rt = 3.74 min.

Example 537 (General procedure 21) Methyl-phenyl-carbamic acid 4- (5-dimethylamino-naphthalene-1-sulfonylamino)-phenyl ester The title compound was prepared in 14% yield as orange crystals using 5-dimethylamino- naphthalene-1-sulfonyl chloride as the aryl sulfonyl chloride.

HPLC-MS: m/z = 476.0 (M+1); Rt = 4.48 min.

Example 538 (General procedure 21) 2- [4- (Methyl-phenyl-carbamoyloxy)-phenylsulfamoyl]-benzoic acid methyl ester The title compound was prepared in 48% yield as a yellow oil using 2-chlorosulfonyl-benzoic acid methyl ester as the aryl sulfonyl chloride.

HPLC-MS: m/z = 441. 1 (M+1); Rt = 4.19 min.

Example 539 (General procedure 21) Methyl-phenyl-carbamic acid 4- (3, 4-difluoro-benzenesulfonylamino)-phenyl ester The title compound was prepared in 1 % yield as a clear oil using 3, 4-difluoro- benzenesulfonyl chloride as the aryl sulfonyl chloride.

HPLC-MS: m/z = 419.1 (M+1) ; Rt = 4.23 min.

Example 540 (General procedure 22 and 1) Methyl-phenyl-carbamic acid 4-pyridin-2-ylmethyl-phenyl ester 4-Pyridin-2-ylmethyl-phenol was prepared following general procedure PVe3 using pyridine- 2-carboxaldehyde. Subsequent carbamoylation using general procedure 1 (CH2CI2 was used as solvent) produced the crude product which was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (86%, oil).

'H NMR (400MHz ; CDCI3) : 5 3. 40 (br s, 3H), 4.14 (s, 2H), 7.04-7. 12 (m, 4H), 7.21-7. 26 (m, 3H), 7.32-7. 40 (m, 4H), 7.55 (t, 1H), 8.52 (d, 1 H).

Example 541 (General procedure 22 and 1) Methyl-phenyl-carbamic acid 4-pyridin-3-ylmethyl-phenyl ester 4-Pyridin-3-ylmethyl-phenol was prepared following general procedure PVe3 using pyridine- 3-carboxaldehyde. Subsequent carbamoylation using general procedure 1 (CH2CI2 was used as solvent) produced the crude product which was purified by flash chromatography (Quad flash 12, EtOAc-heptane) (50%, oil).

1H NMR (400MHz ; Ceci3) : a 3.42 (brs, 3H), 3.96 (s, 2H), 7.03-7. 42 (m, 11H), 8.46 (d, 1H), 8.49 (d, 1 H).

Example 542 (General procedure 22 and 1) Methyl-phenyl-carbamic acid 4- (4-trifluoromethyl-benzyl)-phenyl ester 4- (4-Trifluoromethyl-benzyl)-phenol was prepared following general procedure PVe3 using 4- trifluoromethylbenzaldehyde. Subsequent carbamoylation using general procedure 1 (CH2CI2 was used as solvent) produced the crude product which was purified by flash chromatogra- phy (Quad flash 12, EtOAc-heptane) (92%, oil).

'H NMR (400MHz ; CDCI3) : a 3.42 (br s, 3H), 4.00 (s, 2H), 7.06 (br s, 2H), 7.13 (d, 2H), 7.24- 7.40 (m, 7H), 7.52 (d, 2H).

Example 543 (General procedure 22 and 1) Methyl-phenyl-carbamic acid 4-thiophen-3-ylmethyl-phenyl ester 4-Thiophen-3-ylmethyl-phenol was prepared following general procedure PVe3 using thio-

phene-3-carboxaldehyde. Subsequent carbamoylation using general procedure 1 (CH2CI2 was used as solvent) produced the crude product which was purified by flash chromatogra- phy (Quad flash 12, EtOAc-heptane) (83%, oil).

'H NMR (400MHz ; CDCI3) : 6 3. 42 (bs, 3H), 3.95 (s, 2H), 6.86-7. 39 (m, 12H).

Example 544 (General procedure 22 and 1) Methyl-phenyl-carbamic acid 4-thiophen-2-ylmethyl-phenyl ester 4-Thiophen-2-ylmethyl-phenol phenol was prepared following general procedure PVe3 using thiophene-3-carboxaldehyde. Subsequent carbamoylation using general procedure 1 (CH2C12 was used as solvent) produced the crude product which was purified by flash chromatogra- phy (Quad flash 12, EtOAc-heptane) (83%, oil).

H NMR (400MHz ; CDCI3) : my 3.40 (br s, 3H), 4.13 (s, 2H), 6.78 (dd, 1H), 6.90 (dd, 1H), 7.04 (br d, 2H), 7.13 (dd, 1 H), 7.20-7. 39 (m, 7H). HPLC-MS: m/z = 324.1 (M+1); Rt = 4. 82 min.

Example 545 4-Hydroxy-piperidine-1-carboxylic acid 4- [2- (toluene-4-sulfonylamino)-ethyl]-phenyl ester N-Boc protected tyramin (10 mmol), triethylamine (10 mmol) and 3- [4- (tert-Butyl-dimethyl- silanyloxy)-piperidine-1-carbonyl]-1-methyl-3H-imidazol-1-iu m ; iodide (10 mmol) in MeCN (25 mL) was stirred at room temperature for 16 hours. Acetonitrile was removed by evaporation and the crude product was purified by flash chromatography (Quad flash 40, EtOAc-heptane 1: 2) providing 72% 4-tert-butylsilanyloxy-piperidine-1-carboxylic acid 4-(2-ter- butoxycarbonylamino-ethyl)-phenyl ester. This was deprotected by stirring with a 3.2 M solu- tion of HCI in Et2O (50 mL) for 3 h at rt and subsequently washed with ether to give 91 % of 4- (4-hydroxy-piperidine-1-carbonyloxy)-phenyl-ammonium ; chloride as a solid. This compound was N-tosylated as described for methyl-phenyl-carbamic acid 4- [2- (toluene-4- sulfonylamino)-ethyl]-phenyl ester to give the title compound in 26% yield as yellow crystals after purification by flash chromatography (Quad flash 12, CH2CI2-MeOH 95: 5).

HPLC-MS: m/z = 391.0 (M+1); Rt = 3.04 min.

Example 546 4-Hydroxy-piperidine-1-carboxylic acid 4- [2- (5-pyridin-2-yl-thiophene-2-sulfonylamino)-ethyl]- phenyl 4- (4-Hydroxy-piperidine-l-carbonyloxy)-phenyl-ammonium ; chloride (see above) was N-

sulfonylated as described for methyl-phenyl-carbamic acid 4- [2- (5-pyridin-2-yl-thiophene-2- sulfonylamino)-ethyl]-phenyl ester to give the title compound in 59% yield as an oil after puri- fication by preparative HPLC (Gilson).

HPLC-MS: m/z = 488.0 (M+1); Rt = 3.10 min.

Example 547 4-Hydroxy-piperidine-1-carboxylic acid 4- (5-pyridin-2-yl-thiophene-2-sulfonylamino)-phenyl ester N-Boc protected 4-aminophenol (10 mmol), triethylamine (10 mmol) and 3- [4- (tert-Butyl- dimethyl-silanyloxy)-piperidine-1-carbonyl]-1-methyl-3H-imid azol-1-ium ; iodide (10 mmol) in MeCN (25 mL) was stirred at room temperature for 16 hours. Acetonitrile was removed by evaporation and the crude product was purified by flash chromatography (Quad flash 40, EtOAc-heptane 1: 2) providing 64% 4-tert-butylsilanyloxy-piperidine-1-carboxylic acid 4-tert- butoxycarbonylamino-phenyl ester. This was deprotected by stirring with a 3.2 M solution of HCI in Et20 (50 mL) for 3 h at rt and subsequently washed with ether to give 91 % of 4- (4- Hydroxy-piperidine-1-carbonyloxy)-phenyl-ammonium ; chloride as a hygroscopic solid. This compound was N-sulfonylated as described for methyl-phenyl-carbamic acid 4- [2- (5-pyridin- 2-yl-thiophene-2-sulfonylamino)-ethyl]-phenyl ester to give the title compound in 1 % yield as crystals after purification by preparative HPLC (Gilson).

HPLC-MS: m/z = 482.8 (M+1); Rt = 1.01 min.

Example 548 Methyl-phenyl-carbamic acid 4- [2- (4-amino-benzenesulfonylamino)-ethyl]-phenyl ester Methyl-phenyl-carbamic acid 4- [2- (4-nitro-benzenesulfonylamino)-ethyl]-phenyl ester, 5% palladium on carbon, and ethanol were stirred under hydrogen at 1 bar and rt for 16 h. Filtra- tion and removal of ethanol produced the title compound in 94% yield as an oil.

HPLC-MS: m/z = 426.1 (M+1); Rt = 3.61 min.

Example 549 Methyl-phenyl-carbamic acid 4-{2-[(pyridine-3-carbonyl)-amino]-ethyl}-phenyl ester A solution of 3-pyridinecarboxylic acid (0. 3 mmol), EDAC (0.36 mmol) and triethylamine (0.36 mmol) in CH2CI2 (10 mL) was added N-hydroxybenzoetriazole and N-methyl-N-phenyl- carbamic acid 4- (2-amino-ethyl) phenyl ester as its TFA salt (0.3 mmol). The mixture was stir-

stirred 16 h at rt and purified by preparative HPLC (Gilson) to give the title compound in 15% yield as an oil.

HPLC-MS: m/z = 376.1 (M+1); Rt = 3.01 min.

Example 550 Methyl-phenyl-carbamic acid 4- [2- (2-dimethylamino-acetylamino)-ethyl]-phenyl ester A solution of N, N-dimethylglycine, HCI (0.3 mmol), EDAC (0.36 mmol) and triethylamine (1.0 mmol) in CH2CI2 (10 mL) was added N-hydroxybenzoetriazole and N-methyl-N-phenyl- carbamic acid 4- (2-amino-ethyl) phenyl ester as its TFA salt (0.3 mmol). The mixture was stir- red 16 h at rt and purified by preparative HPLC (Gilson) to give the title compound in 66% yield as an oil.

HPLC-MS: m/z = 356.4 (M+1); Rt = 2.09 min.

Example 551 (General procedure 23) Methyl-phenyl-carbamic acid 2- (toluene-4-sulfonyl)-1, 2,3, 4-tetrahydro-isoquinolin-7-yl ester The title compound was prepared using methyl-phenyl-carbamic acid 4- [2- (toluene-4- sulfonylamino)-ethyl]-phenyl ester as the sulfonamide. The crude product was purified by flash chromatography (Quad flash 12, EtOAc-heptane 2: 3) (71%, yellow oil).

HPLC-MS: m/z = 437.4 (M+1); Rt = 4.43 min.

Example 552 Methyl-phenyl-carbamic acid 4- [4- (2-pyrrolidin-1-yl-ethoxy)-benzyl]-phenyl ester To a stirred solution of 1- [2- (4-bromo-phenoxy)-ethyl]-pyrrolidine (2.89 g, 10.7 mmol) in THF (30 mL) was added dropwise 1.6 M solution in hexanes n-BuLi (7 mL, 10.2 mmol) over a 5- min period at-78°C. The mixture was stirred at-78°C for 15 min before 4- trimethylsilyloxybenzaldehyde (2. 08 g, 10.7 mmol) was added. The mixture was allowed to warm to rt during 20 min and quenched with water. Extraction with CH2CI2, drying (MgS04), filtration and evaporation provided the crude diarylmethanol which was dissolved in CH2CI2 (30 mL) and stirred with triethylsilane (4 mL) and TFA (5 mL) for 16 h at rt. Evaporation gave 3.0 g (84%) 4- [4- (2-pyrrolidin-1-yi-ethoxy)-benzyl]-phenol. This was carbamoylated using general procedure 1 (CH2CI2 was used as solvent) to give the title product after purification by preparative HPLC (Gilson) (35%, oil).

HPLC-MS: m/z = 431.5 (M+1); Rt = 2.93 min.

Example 553 (General procedure 24) 4-Hydroxy-piperidine-1-carboxylic acid 4-pyridin-2-ylmethyl-phenyl ester The title compound was prepared as its hydrochloride using 4-pyridin-2-ylmethyl-phenol as the phenol.

'H NMR (300MHz ; D20) : # 1.50 (br s, 2H), 1.90 (d, 2H), 3.04-3. 27 (m, 2H), 3.78-4. 08 (m, 3H), 4.41 (s, 2H), 7.07 (d, 2H), 7.30 (d, 2H), 7.79-7. 85 (m, 2H), 8.40 (dt, 1 H), 8.55 (d, 1 H).

Example 554 (General procedure 24) 4-Hydroxy-piperidine-1-carboxylic acid 4-pyridin-3-ylmethyl-phenyl ester The title compound was prepared as its hydrochloride using 4-pyridin-3-ylmethyl-phenol as the phenol.

'H NMR (300MHz ; D20) : # 1.48 (br s, 2H), 1.90 (d, 2H), 3.03-3. 26 (m, 2H), 3.80-4. 05 (m, 3H), 4.18 (s, 2H), 7.03 (d, 2H), 7.25 (d, 2H), 7.40 (dd, 1H), 8.40 (d, 1H), 8. 54-8.57 (m, 2H).

Example 555 (General procedure 24) 4-Hydroxy-piperidine-1-carboxylic acid 4- (4-trifluoromethyl-benzyl)-phenyl ester The title compound was prepared using 4- (4-trifluoromethyl-benzyl)-phenol as the phenol.

'H NMR (300MHz ; D20) : F 1.43-1. 55 (m, 2H), 1.76-1. 88 (m, 2H), 3.10-3. 29 (m, 2H), 3.79- 3.94 (m, 5H), 6.97 (d, 2H), 7.08 (d, 2H), 7.20 (d, 1H), 7.45 (d, 2H).

Example 556 (General procedure 23) Methyl-phenyl-carbamic acid 2- [4- (2-pyrrolidin-1-yl-ethoxy)-benzenesulfonyl]-1, 2,3, 4- tetrahydro-isoquinolin-7-yl ester The title compound was prepared using methyl-phenyl-carbamic acid 4- {2- [4- (2-pyrrolidin-1- yl-ethoxy)-benzenesulfonylamino]-ethyl}-phenyl ester as the sulfonamide. The crude product was purified by preparative HPLC (Gilson) and isolated as its TFA salt (45%, foam).

HPLC-MS : m/z= 536.2 (M+1) ; Rt = 3.10 min.

Example 557 Methyl-phenyl-carbamic acid 4- {2- [ (1-methyl-piperidine-4-carbonyl)-amino]-ethyl}-phenyl es- ter

A solution of 1-methylpiperidine-4-carboxylic acid (0.3 mmol), EDAC (0.36 mmol) and triethy- lamine (1.0 mmol) in CH2CI2 (10 mL) was added N-hydroxybenzoetriazole and N-methyl-N- phenyl-carbamic acid 4- (2-amino-ethyl) phenyl ester as its TFA salt (0.3 mmol). The mixture was stirred 16 h at rt and purified by preparative HPLC (Gilson) to give the title compound in 5% yield as an oil.

HPLC-MS: m/z = 396.4 (M+1); Rt = 2.03 min.

Example 558 (General procedure 23) Methyl-phenyl-carbamic acid 2- (3, 4-difluoro-benzenesulfonyl)-1, 2,3, 4-tetrahydro-isoquinolin- 7-yl ester The title compound was prepared using methyl-phenyl-carbamic acid 4- [2- (3, 4-difluoro- benzenesulfonylamino)-ethyl]-phenyl ester as the sulfonamide. The crude product was puri- fied by preparative HPLC (Gilson) (24%, oil).

HPLC-MS: m/z = 481.0 (M+23); Rt = 4.73 min.

Example 559 (General procedure 23) Methyl-phenyl-carbamic acid 1-methyl-2- (toluene-4-sulfonyl)-1, 2,3, 4-tetrahydro-isoquinolin-7- yl ester The title compound was prepared using methyl-phenyl-carbamic acid 4- [2- (toluene-4- sulfonylamino)-ethyl]-phenyl ester as the sulfonamide and acetaldehyde in stead of formal- dehyde. The crude product was purified by preparative HPLC (Gilson) (22%, brown oil).

HPLC-MS: m/z = 451.5 (M+1); Rt = 4.43 min.

Example 560 (General procedure 23) Methyl-phenyl-carbamic acid 2- [4- (4-methyl-piperazin-1-yl)-benzenesulfonyl]-1, 2,3, 4- tetrahydro-isoquinolin The title compound was prepared using methyl-phenyl-carbamic acid 4- {2- [4- (4-methyl- piperazin-1-yl)-benzenesulfonylamino]-ethyl}-phenyl ester as the sulfonamide. The crude product was purified by preparative HPLC (Gilson) and isolated as its TFA salt (79%, crys- tals).

HPLC-MS: m/z = 521.5 (M+1); Rt = 2.65 min.

Example 561 (General procedure 23) Methyl-phenyl-carbamic acid 1-methyl-2- [4- (4-methyl-piperazin-I-yl)-benzenesulfonyl]- 1,2, 3, 4-tetrahydro-isoquinolin-7-yl ester The title compound was prepared using methyl-phenyl-carbamic acid 4- {2- [4- (4-methyl- piperazin-1-yl)-benzenesulfonylamino]-ethyl}-phenyl ester as the sulfonamide and acetalde- hyde in stead of formaldehyde. The crude product was purified by preparative HPLC (Gilson) (12%, brown oil).

HPLC-MS: m/z = 535.4 (M+1); Rt = 2.69 min.

Example 562 3, 3-Dimethyl-4- {2- [4- (methyl-phenyl-carbamoyloxy)-phenyl]-ethylcarbamoyl}-butyric acid A solution of 3, 3-dimethylglutaric anhydride (0.3 mmol), diisopropylethylamine (0.30 mmol) and N-methyl-N-phenyl-carbamic acid 4- (2-amino-ethyl) phenyl ester as its TFA salt (0.3 mmol) in CH2CI2 (3 mL) was stirred 1 h at rt. The mixture was washed with water and brine, dried and evaporated to give the title compound in 95% yield as an oil.

HPLC-MS: m/z = 413.2 (M+1) ; Rt = 3.20 min.

Example 563 Methyl-phenyl-carbamic acid 4- {2- [4- (4-methyl-piperazin-1-yl)-benzoylamino]-ethyl}-phenyl ester A solution of 4- (4-methylpiperazino) benzoic acid (0.3 mmol), EDAC (0.36 mmol) and triethyl- amine (1.0 mmol) in CH2CI2 (10 mL) was added N-hydroxybenzoetriazole and N-methyl-N- phenyl-carbamic acid 4- (2-amino-ethyl) phenyl ester as its TFA salt (0.3 mmol). The mixture was stirred 16 h at rt and purified by preparative HPLC (Gilson) to give the title compound in 54% yield as its crystalline hydrochloride after treatment with HCI in diethyl ether.

HPLC-MS: m/z = 473.2 (M+1); Rt = 2.22 min.

Example 564 Methyl-phenyl-carbamic acid 4- {2- [4- (4-methyl-piperazin-1-ylmethyl)-benzoylamino]-ethyl}- phenyl ester A solution of 4- (4-methylpiperazinyl) methyl benzoic acid (0.3 mmol), EDAC (0.36 mmol) and triethylamine (1.0 mmol) in CH2CI2 (10 mL) was added N-hydroxybenzoetriazole and N-

methyl-N-phenyl-carbamic acid 4- (2-amino-ethyl) phenyl ester as its TFA salt (0.3 mmol). The mixture was stirred 16 h at rt and purified by preparative HPLC (Gilson) to give the title com- pound in 25% yield as its crystalline hydrochloride after treatment with HCI in diethyl ether..

HPLC-MS: m/z= 487.3 (M+1); Rt = 2.13 min.

Example 565 Methyl-phenyl-carbamic acid 4- [2- (4, 4-dimethyl-2, 6-dioxo-piperidin-1-yl)-ethyl]-phenyl ester A solution of 3, 3-dimethylglutaric anhydride (0.3 mmol), diisopropylethylamine (0.30 mmol) and N-methyl-N-phenyl-carbamic acid 4- (2-amino-ethyl) phenyl ester as its TFA salt (0.3 mmol) in CH2CI2 (3 mL) was stirred 1 h at rt. Thionylchloride (3 mmol) was added and the mixture was stirred for 2 h at rt. Addition of ethanol (5 mL) followed by evaporation to dry- ness gave a crude product which was purified by flash chromatography (Quad flash 12, EtOAc-heptane 1: 1). This gave the title compound in 23% yield as crystals. Furthermore 3,3- dimethyl-4- {2- [4- (methyl-phenyl-carbamoyloxy)-phenyl]-ethylcarbamoyl}-butyric acid ethyl ester could be isolated in 27% yield as an oil (see characterization below) 'H NMR (400MHz ; CDCI3) : zu 1.04 (s, 6H), 2.47 (s, 4H), 2.79 (t, 2H), 3.42 (br s, 3H), 3.97 (t, 2H), 7.03 (br d, 2H), 7.21-7. 28 (m, 3H), 7.33-7. 41 (m, 4H).

HPLC-MS: m/z = 395.2 (M+1) ; Rt = 4.23 min.

Example 566 3, 3-Dimethyl-4- {2- [4- (methyl-phenyl-carbamoyloxy)-phenyl]-ethylcarbamoyl}-butyric acid ethyl ester For experimental details, see preparation of methyl-phenyl-carbamic acid 4- [2- (4, 4-dimethyl- 2, 6-dioxo-piperidin-1-yl)-ethyl]-phenyl ester.

'H NMR (400MHz ; CDCI3) : a 1.05 (s, 6H), 1.24 (t, 3H), 2.19 (s, 2H), 2.22 (s, 2H), 2.80 (t, 2H), 3.42 (brs, 3H), 3.50 (q, 2H), 4.1 (q, 2H), 6.53 (t, 1H), 7.03 (brd, 2H), 7.18 (d, 2H), 7.26 (t, 1 H), 7.33-7. 41 (m, 4H).

HPLC-MS: mlz = 441. 2 (M+1); Rt = 4. 11 min.

Example 567 Methyl-phenyl-carbamic acid 4-hydroxymethyl-phenyl ester To a solution of 4-hydroxymethylphenol (10 mmol) and 4-diazabicyclo [2.2. 2] octane (DABCO) (10 mmol) in CH2CI2 (30 mL) was added N-methyl-N-phenylcarbamoyl chloride (10 mmol).

The reaction mixture was stirred for 16 hours at rt, added CH2CI2 (20 mL) and washed with 1 M aqueous HCI and brine. The organic phase was dried (MgS04) and evaporated to give the crude product which was purified by FC (Quad flash 40 EtOAc-Heptane 1: 1) to give 2.18 g (85%) of the title compound as an oil.

'H NMR (400MHz ; CDCI3) : s 1.70 (br s, 1 H), 3.40 (br s, 3H), 4.66 (s, 2H), 7.08 (br d, 2H), 7.25-7. 42 (m, 7H); HPLC-MS: m/z = 258.1 (M+1); Rt = 2.99 min.

Example 568 Methyl-phenyl-carbamic acid 4- (2-hydroxy-ethyl)-phenyl ester To a solution of 4- (2-Hydroxyethyl) phenol (10 mmol) and 4-diazabicyclo [2.2. 2] octane (DABCO) (10 mmol) in CH2CI2 (30 mL) was added N-methyl-N-phenylcarbamoyl chloride (10 mmol). The reaction mixture was stirred for 16 hours at rt, added CH2CI2 (20 mL), and washed with 1 M aqueous HCI and brine. The organic phase was dried (MgS04) and evapo- rated to give the 2.69 g (99%) of the title compound as crystals.

'H NMR (400MHz ; CDCI3) : a 1.52 (br s, 1 H), 2. 84 (t, 2H), 3.41 (br s, 3H), 3.81 (t, 2H), 7.04 (brd, 2H), 7.20 (d, 2H), 7.22-7. 42 (m, 5H); HPLC-MS: m/z= 272.1 (M+1); Rt = 3.17 min.

Example 569 (General procedure 1) Methyl-phenyl-carbamic acid 4- (4-dimethylamino-pyridin-2-ylmethyl)-phenyl ester A solution of 2- (dimethylamino) ethanol (32 mmol) in hexane (120 mL) was cooled to-5°C and n-BuLi (64 mmol) was added. After 30 min 4- (dimethylamine=pyridine (16 mmol) was added and the red-orange mixture was stirred for further 1 h. The solution was cooled to-78 °C and 4- (trimethylsilyloxy) benzaldehyde (40 mmol) dissolved in hexane (80 mL) was added and the suspention was allowed to warm to rt over 20 min. The reaction mixture was quenched with water, and the aqueous phase was washed with CH2CI2. The aqueous phase was evaporated to dryness, added Nal (96 mmol) and dissolved in MeCN (160 mL). Addition of trimethylsilylchloride (96 mmol) and stirring at rt for 16h. The purple reaction mixture was evaporated to dryness and treated with an aqueous solution of Na2SO3 and pH was adjusted to 8. Extraction with CH2CI2 gave after evaporation 560 mg (15%) slightly impure 4- (4- dimethylamino-pyridin-2-ylmethyl) phenol as yellow crystals. This was carbamoylated using general procedure 1 (CH2CI2 was used as solvent) to give the title product as its hydrochlo- ride after purification by preparative HPLC (Gilson) and treatment with HCI in Et2O (48%, ligt yellow crystals).

HPLC-MS: m/z = 362.2 (M+1); Rt = 2.27 min.

Example 570 (General procedure 25) Methyl-phenyl-carbamic acid 4- (4-imidazol-1-yl-phenoxymethyl)-phenyl ester The title compound was prepared in 53% yield as light yellow crystals using and 4-imidazol- 1-yl-phenol.'H NMR (400MHz ; CDCl3) : a 3.42 (br s, 3H), 5.08 (s, 2H), 7.03 (d, 2H), 7.12- 7.42 (m, 15H), 7.77 (s, 1 H) ; HPLC-MS: m/z = 400.1 (M+1) ; Rt = 2.62 min.

Example 571 (General procedure 25) Methyl-phenyl-carbamic acid 4- [4- (2-dimethylamino-ethyl)-phenoxymethyl]-phenyl ester The title compound was prepared in 52% yield as colorless crystals using methyl-phenyl- carbamic acid 4-hydroxymethyl-phenyl ester and 4-(2-dimethylaminoethyl)-phenol. 1H NMR (400MHz ; CDCI3) : a 2.85 (s, 6H), 2.98-3. 02 (m, 2H), 3.17-3. 21 (m, 2H), 3.42 (br s, 3H), 5.02 (s, 2H), 6.90 (d, 2H), 7.12 (d, 2H), 7.25-7. 43 (m, 7H); HPLC-MS : m/z = 405.2 (M+1); Rt = 2.91 min.

Example 572 (General procedure 25) Methyl-phenyl-carbamic acid 4- (pyrazol-1-yloxymethyl)-phenyl ester The title compound was prepared in 79% yield as an oil using and 1-hydroxypyrazole.'H NMR (400MHz ; CDCI3) : a 3.42 (br s, 3H), 5.26 (s, 2H), 6.03 (t, 1 H), 6.95 (dd, 1H), 7.11 (br s, 2H), 7.25-7. 42 (m, 8H); HPLC-MS: m/z = 324.1 (M+1); Rt = 3.58 min.

Example 573 (General procedure 25) Methyl-phenyl-carbamic acid 4- (imidazol-1-yloxymethyl)-phenyl ester The title compound was prepared as its TFA salt in 87% yield as a solid using methyl-phenyl- carbamic acid 4-hydroxymethyl-phenyl ester and 1-hydroxyimidazole, hydrochloride. 1H NMR (400MHz ; CDCI3) : s 3.42 (br s, 3H), 5.21 (s, 2H), 6.95 (s, 1 H), 7.16-7. 45 (m, 10H), 8.28 (br s, 1H) ; HPLC-MS: m/z = 324.1 (M+1); Rt = 1.92 min.

Example 574 (General procedure 25) Methyl-phenyl-carbamic acid 4- (2-oxo-2H-pyridin-1-ylmethyl)-phenyl ester

The title compound was prepared in 29% yield as an oil using methyl-phenyl-carbamic acid 4- (2-hydroxy-ethyl)-phenyl ester and 2-hydroxypyridine. In addition 50% of the isomeric methyl-phenyl-carbamic acid 4- [2- (pyridin-2-yloxy)-ethyl]-phenyl ester was isolated, see characterization below.'H NMR (400MHz ; CDCI3) : a 3.05 (t, 2H), 3.41 (br s, 3H), 4.14 (s, 2H), 6.08 (t, 1 H), 6.66 (d, 1 H), 6.90 (dd, 1 H), 7.02 (br s, 2H), 7.10 (d, 2H), 7.25-7. 42 (m, 6H); HPLC-MS: m/z = 349.2 (M+1); Rt = 3.04 min.

Example 575 (General procedure 25) Methyl-phenyl-carbamic acid 4- [2- (pyridin-2-yloxy)-ethyl]-phenyl ester The title compound was prepared in 50% yield as an oil using methyl-phenyl-carbamic acid 4- (2-hydroxy-ethyl)-phenyl ester and 2-hydroxypyridine. In addition 29% of the isomeric methyl-phenyl-carbamic acid 4- (2-oxo-2H-pyridin-1-ylmethyl)-phenyl ester was isolated, see characterization above.'H NMR (400MHz ; CDCI3) : 8 3.08 (t, 2H), 3.41 (br s, 3H), 4.49 (s, 2H), 6.73 (d, 1H), 6.88 (dd, 1H), 7.05 (brd, 2H), 7.22-7. 42 (m, 7H), 7.61 (dt, 1H), 8.18 (dd, 1 H) ; HPLC-MS : m/z = 349.2 (M+1) ; Rt = 3.97 min.

Example 576 (General procedure 25) Methyl-phenyl-carbamic acid 4- [2- (4-imidazol-1-yl-phenoxy)-ethyl]-phenyl ester The title compound was prepared as its TFA salt in 62% yield as an oil using methyl-phenyl- carbamic acid 4- (2-hydroxy-ethyl)-phenyl ester and 4-imidazol-1-yl-phenol.

1H NMR (400MHz ; CDCI3) : 5 3. 11 (t, 2H), 3.42 (br s, 3H), 4.22 (s, 2H), 7.00-7. 10 (m, 5H), 7.25-7. 42 (m, 9H), 7.52 (s, 1 H), 8. 81 (s, 1 H) ; HPLC-MS: m/z = 414.2 (M+1); Rt = 2.73 min.

Example 577 (General procedure 25) Methyl-phenyl-carbamic acid 4- {2- [4- (2-dimethylamino-ethyl)-phenoxy]-ethyl}-phenyl ester The title compound was prepared as its TFA salt in 92% yield as an oil using methyl-phenyl- carbamic acid 4- (2-hydroxy-ethyl)-phenyl ester and 4- (2-dimethylaminoethyl)-phenol.

HPLC-MS: m/z = 419.2 (M+1) ; Rt = 2.77 min.

Example 578 (General procedure 25) Methyl-phenyl-carbamic acid 4- [2- (pyrazol-1-yloxy)-ethyl]-phenyl ester The title compound was prepared in 62% yield as an oil using methyl-phenyl-carbamic acid

4- (2-hydroxy-ethyl)-phenyl ester and 1-hydroxypyrazole.

1H NMR (400MHz ; CDC ! s) : F 3.02 (t, 2H), 3.42 (br s, 3H), 4.50 (t, 2H), 6.16 (t, 1 H), 7.05 (br d, 2H), 7.20-7. 41 (m, 9H); HPLC-MS: m/z = 338.2 (M+1); Rt = 3.74 min.

Example 579 (General procedure 25) Methyl-phenyl-carbamic acid 4- [2- (imidazol-1-yloxy)-ethyl]-phenyl ester The title compound was prepared as its TFA salt in 79% yield as an oil using methyl-phenyl- carbamic acid 4- (2-hydroxy-ethyl)-phenyl ester and 1-hydroxyimidazole hydrochlorid.

'H NMR (400MHz ; CDCI3) : a 3.06 (t, 2H), 3.42 (br s, 3H), 4.52 (t, 2H), 7.08-7. 42 (m, 11 H), 8. 53 (s, 1 H) ; HPLC-MS: m/z = 338.2 (M+1); Rt = 2.18 min.

Example 580 (General procedure 1) Methyl-phenyl-carbamic acid 4- (5-methyl-pyridin-2-ylmethyl)-phenyl ester To a stirred solution of 2-bromo-5-methylpyridine (3. 45 g, 20 mmol) in THF (10 mL) was added dropwise 1.6 M solution in hexanes n-BuLi (12 mL, 19.2 mmol) over a 10-min period at-78°C. The mixture was stirred at-78°C for 2 min before 4-trimethylsilyloxybenzaldehyde (4.2 g, 21.6 mmol) dissolved in THF (10 mL) was added. The mixture was allowed to warm to - 40 °C and quenched with water. The pH of the aqueous phase was adjusted to 7 which causes precipitation of 4- [hydroxy- (5-methyl-pyridin-2-yl)-methyl] phenol. This was isolated by filtration to give 1.13 g (27%) of 4- [hydroxy- (5-methyl-pyridin-2-yi)-methyl] phenol as crystals.

This intermediate was dissolved in CH2CI2 (15 mL) and stirred with triethylsilane (4 mL) and TFA (5 mL) for 16 h at 50 °C. Evaporation gave 99% of 4- (5-methyl-pyridin-2-ylmethyl) phenol as a hygroscopic solid. This was carbamoylated using general procedure 1 (CH2CI2 was used as solvent and N-phenyl-N-methyl carbamoyl chlorid) to give 99% of the title product as its crystalline hydrochloride after purification by flash chromatography (Quad flash 12, EtOAc-heptane) and treatment with HCI in Et2O.

1H NMR (400MHz ; CDCI3) : 2.50 (s, 3H), 3.41 (br s, 3H), 4.57 (s, 2H), 7.10 (br s, 2H), 7.25- 7.42 (m, 8H), 8.00 (dd, 1 H), 8.46 (br s, 1 H) ; HPLC-MS: m/z = 333.1 (M+1); Rt = 2.60 min.

Example 581 (General procedure 24) 4-Hydroxy-piperidine-1-carboxylic acid 4- (5-methyl-pyridin-2-ylmethyl)-phenyl ester The title compound was prepared as its hydrochloride using of 4- (5-methyl-pyridin-2-

ylmethyl) phenol as the phenol.

'H NMR (300MHz ; CDCI3) : a 1.57-1. 67 (m, 3H), 1.95 (d, 2H), 2.51 (s, 3H), 3.21-3. 40 (m, 2H), 3.90-4. 05 (m, 3H), 4.58 (s, 2H), 7.11 (d, 2H), 7.38 (d, 2H), 7.45 (d, 1 H), 8.02 (d, 1 H), 8.48 (br s, 1 H).

Example 582 (General procedure 25) Methyl-phenyl-carbamic acid 4- (4-oxo-4H-pyridin-1-ylmethyl)-phenyl ester The title compound was prepared in 33% yield as colorless crystals using methyl-phenyl- carbamic acid 4-hydroxymethyl-phenyl ester and 4-hydroxypyridine.'H NMR (400MHz ; CDCI3) : a 3.43 (br s, 3H), 4.92 (s, 2H), 6.43 (d, 2H), 7.17 (br s, 4H), 7.22-7. 42 (m, 9H); HPLC-MS: m/z = 335.0 (M+1); Rt = 2.55 min.

Example 583 (General procedure 25) Methyl-phenyl-carbamic acid 4- [2- (pyridin-3-yloxy)-ethyl]-phenyl ester The title compound slightly contaminated with tributylphosphine oxide was prepared in 80% yield as an oil using methyl-phenyl-carbamic acid 4- (2-hydroxy-ethyl)-phenyl ester and 3- hydroxypyridine.

'H NMR (400MHz ; CDCI3) : a 3.11 (t, 2H), 3.42 (br s, 3H), 4.23 (t, 2H), 7.07 (br d, 2H), 7.24- 7.41 (m, 9H), 8.29 (br s, 1 H), 8.40 (br s, 1 H); HPLC-MS: m/z = 349.2 (M+1); Rt = 2.87 min.

Example 584 (General procedure 25) Methyl-phenyl-carbamic acid 4- (2-oxo-2H-pyridin-1-ylmethyl)-phenyl ester The title compound was prepared in 66% yield as an oil using methyl-phenyl-carbamic acid 4-hydroxymethyl-phenyl ester and 2-hydroxypyridine.'H NMR (400MHz ; CDCI3) : 8 3.42 (br s, 3H), 5.12 (s, 2H), 6.13 (t, 1H), 6.60 (d, 1H), 7.10 (brs, 2H), 7.22-7. 41 (m, 9H); HPLC-MS : m/z = 335.2 (M+1); Rt = 2.97 min.

Example 585 (General procedure 25) Methyl-phenyl-carbamic acid 4- (pyridin-3-yloxymethyl)-phenyl ester The title compound was prepared in 43% yield as an oil using methyl-phenyl-carbamic acid 4-hydroxymethyl-phenyl ester and 3-hydroxypyridine.'H NMR (400MHz ; CDCI3) : 8 3.44 (br

s, 3H), 5.12 (s, 2H), 7.17 (brs, 2H), 7.27-7. 46 (m, 9H), 8.29 (brs, 1H), 8.49 (brs, 1H) ; HPLC- MS: m/z = 335.0 (M+1) ; Rt = 2.74 min.

Example 586 (General procedure 26) Methyl-phenyl-carbamic acid 4- [2- (2, 5-dioxo-pyrrolidin-1-yl)-ethyl]-phenyl ester The title compound was prepared in 85% yield as crystals using methyl-phenyl-carbamic acid 4- (2-hydroxy-ethyl)-phenyl ester and succinimide.'H NMR (400MHz ; CDCI3) : 8 2. 65 (s, 4H), 2. 86 (t, 2H), 3.41 (br s, 3H), 3.72 (t, 2H), 7.04 (br d, 2H), 7.19 (d, 2H), 7.26-7. 42 (m, 5H); HPLC-MS: m/z= 353.2 (M+1); Rt= 3.17 min.

Example 587 (General procedure 26) Methyl-phenyl-carbamic acid 4- [2- (1, 3-dioxo-1, 3-dihydro-pyrrolo [3,4-] pyridin-2-yl)-ethyl]- phenyl ester The title compound was prepared in 58% yield as crystals using methyl-phenyl-carbamic acid 4- (2-hydroxy-ethyl)-phenyl ester and 3, 4-pyridinedicarboximide.'H NMR (400MHz ; CDCI3) : a 2. 98 (t, 2H), 3.40 (br s, 3H), 3.93 (t, 2H), 7.05 (br d, 2H), 7.20-7. 42 (m, 7H), 7.73 (dd, 1 H), 9.06 (d, 1H), 9.12 (d, 1H) ; HPLC-MS: m/z= 402.1 (M+1); Rt = 3.56 min.

Example 588 (General procedure 26) Methyl-phenyl-carbamic acid 4- (1-methyl-1 H-imidazol-2-ylsulfanylmethyl)-phenyl ester The title compound was prepared as its TFA salt in 22% yield as an oil using methyl-phenyl- carbamic acid 4-hydroxymethyl-phenyl ester and 2-mercapto-1-methylimidazole. 1H NMR (400MHz ; CDCI3) : a 3.34 (s, 3H), 3.40 (br s, 3H), 4.30 (s, 2H), 6.98 (br s, 2H), 7.08-7. 11 (m, 3H), 7.27-7. 42 (m, 5H), 7.48 (d, 1H) ; HPLC-MS: m/z= 354.1 (M+1); Rt = 2.12 min.

Example 589 (General procedure 26) Methyl-phenyl-carbamic acid 4-tetrazol-1-ylmethyl-phenyl ester The title compound was prepared in 6% yield as an oil using methyl-phenyl-carbamic acid 4- hydroxymethyl-phenyl ester and tetrazole.'H NMR (400MHz ; CDC13) : a 3.42 (br s, 3H), 5.57 (s, 2H), 7.17 (br s, 2H), 7.26-7. 42 (m, 7H), 8. 52 (s, 1 H) ; HPLC-MS: m/z = 332.0 (M+23); Rt = 3.24 min.

Example 590 (General procedure 26) Methyl-phenyl-carbamic acid 4- (2, 5-dioxo-pyrrolidin-1-ylmethyl)-phenyl ester The title compound was prepared in 57% yield as beige crystals using methyl-phenyl- carbamic acid 4-hydroxymethyl-phenyl ester and succinimide. 1H NMR (400MHz ; CDCI3) : 8 2.68 (s, 4H), 3.41 (br s, 3H), 4.60 (s, 2H), 7.04 (br d, 2H), 7.23-7. 41 (m, 7H); HPLC-MS : m/z = 339. 1 (M+1); Rt = 3. 40 min.

Example 590 (General procedure 26) Methyl-phenyl-carbamic acid 4-[2-(2-thioxo-2H-pyridin-1-yl)-ethyl]-phenyl ester The title compound was prepared in 25% yield as an oil using methyl-phenyl-carbamic acid 4- (2-hydroxy-ethyl)-phenyl ester and 2-mercaptopyridine. HPLC-MS: m/z = 365.2 (M+1); Rt = 4.08 min.

Example 591 (General procedure 26) Methyl-phenyl-carbamic acid 4- (1, 3-dioxo-1, 3-dihydro-pyrrolo [3,4) pyridin-2-ylmethyl)-phenyl ester The title compound was prepared in 21 % yield as an oil using methyl-phenyl-carbamic acid 4-hydroxymethyl-phenyl ester and 3, 4-pyridinedicarboximide.'H NMR (400MHz ; CDCI3) : a 3.40 (br s, 3H), 4.82 (s, 2H), 7.06 (d, 2H), 7.22-7. 44 (m, 8H), 7.73 (d, 1 H), 9.04 (d, 1 H), 9.12 (s, 1 H) ; HPLC-MS: m/z = 388.0 (M+1); Rt = 3.80 min.

Example 592 (General procedure 26) Methyl-phenyl-carbamic acid 4- [1, 2,4] triazol-1-ylmethyl-phenyl ester The title compound was prepared as its TFA salt in 27% yield as an oil using methyl-phenyl- carbamic acid 4-hydroxymethyl-phenyl ester and 1,2, 4-triazole.'H NMR (400MHz ; CDCI3) : 8 3.42 (br s, 3H), 5.34 (s, 2H), 7.15 (br d, 2H), 7.26-7. 43 (m, 7H), 8.10 (s, 1 H), 8.38 (s, 1 H) ; HPLC-MS: m/z = 309.1 (M+1); Rt = 2. 74 min.

Example 593 (General procedure 26) Methyl-phenyl-carbamic acid 4-(2-thioxo-2H-pyridin-1-ylmethyl)-phenyl ester

The title compound was prepared in 14% yield as an oil using methyl-phenyl-carbamic acid 4-hydroxymethyl-phenyl ester and 2-mercaptopyridine. HPLC-MS: m/z = 351.1 (M+1) ; Rt = 3.95 min.

Example 594 (General procedure 26) Methyl-phenyl-carbamic acid 4- [2- (l-methyl-1 H-imidazol-2-yisulfanyl)-ethyl]-phenyl ester The title compound was prepared as its TFA salt in 37% yield as an oil using methyl-phenyl- carbamic acid 4- (2-hydroxy-ethyl)-phenyl ester and 2-mercapto-1-methylimidazole. NMR (400MHz ; CDCI3) : 8 3.01 (t, 2H), 3.40 (br s, 3H), 3.47 (s, 1 H), 3.64 (t, 2H), 6.92 (br d, 2H), 6. 98 (s, 1 H), 7.08 (d, 2H), 7.26-7. 43 (m, 6H); HPLC-MS: m/z = 368.2 (M+1); Rt = 2.30 min.

Example 595 (General procedure 26) Methyl-phenyl-carbamic acid 4- (2-tetrazol-1-yl-ethyl)-phenyl ester The title compound was prepared in 10% yield as an oil using methyl-phenyl-carbamic acid 4- (2-hydroxy-ethyl)-phenyl ester and tetrazol. NMR (400MHz ; CDCI3) : J 3.19 (t, 2H), 3.40 (br s, 3H), 3.47 (s, 1 H), 4.61 (t, 2H), 6.98-7. 07 (m, 4H), 7.25-7. 42 (m, 5H), 8.26 (s, 1 H) ; HPLC-MS: m/z= 324.1 (M+1); Rt = 3.36 min.

Example 596 (General procedure 26) Methyl-phenyl-carbamic acid 4- [2- (pyrimidin-2-yloxy)-ethyl]-phenyl ester The title compound was prepared in 24% yield as light yellow crystals using methyl-phenyl- carbamic acid 4- (2-hydroxy-ethyl)-phenyl ester and 2-hydroxypyrimidine. NMR (400MHz ; CDCI3) : 3.11 (t, 2H), 3.42 (br s, 3H), 4.54 (t, 2H), 6.93 (t, 1 H), 7.05 (d, 2H), 7.25-7. 42 (m, 7H), 8.51 (d, 2H); HPLC-MS: m/z = 350.2 (M+1); Rt = 2.86 min.

Example 597 (General procedure 26) Methyl-phenyl-carbamic acid 4-[2-(pyridin-4-ylsulfanyl)-ethyl]-phenyl ester The title compound was prepared as its TFA salt in 5% yield as an oil using methyl-phenyl- carbamic acid 4- (2-hydroxy-ethyl)-phenyl ester and 4-mercaptopyridine. NMR (400MHz ; CDCI3) : 8 3.07 (t, 2H), 3.36 (t, 2H), 3.44 (br s, 3H), 7.06 (br d, 2H), 7.20 (d, 2H), 7.25-7. 43

(m, 7H), 8.51 (d, 2H); HPLC-MS: m/z = 365.2 (M+1); Rt = 2.53 min.

Example 598 (General procedure 12) 4- (3-Amino-phenyl)-piperidine-1-carboxylic acid 4- (5-trifluoromethyl-pyridin2-yloxy)-phenyl ester, The title product was prepared from 4- (3-aminophenyl) piperidine (released form the correspon- dent hydrochloride by a standard procedure) and 4- (5-trifluoromethyl-pyridin-2-yloxy)-phenyl chloroformate, preparative HPLC (method C) (reaction performed in a mixture of dichloro- methane and dimethylformamide, 5: 3). 1.7 M HCI in ethyl acetate was added to the pooled frac- tions containing the title product, and the fractions was evaporated to dryness (7%, light yellow solid). HPLC-MS m/z = (M+1) 458.0, Rt: 3.09 min.

Example 599 (General procedure 26) Methyl-phenyl-carbamic acid 4- [2- (1-pyridin-3-yl-1 H-imidazol-2-ylsulfanyl)-ethyl]-phenyl ester The title compound was prepared as its TFA salt in 5% yield as an oil using methyl-phenyl- carbamic acid 4- (2-hydroxy-ethyl)-phenyl ester and 3- (2thio-1 H-imidazol-1-yl) pyridine. NMR (400MHz ; CDCI3) : a 2.95 (t, 2H), 3.42 (br s, 2H), 3.56 (t, 3H), 6.98 (br d, 2H), 7.05 (d, 2H), 7.15 (d, 1H), 7.23-7. 43 (m, 5H), 7.48 (d, 1H), 7.53 (dd, 1H), 7.70 (ddd, 1H), 8.65 (d, 1H), 8.77 (dd, 1 H) ; HPLC-MS: m/z = 431.2 (M+1) ; Rt = 2.79 min.

Example 600 (General procedure 26) Methyl-phenyl-carbamic acid 4- [2- (1, 3-dioxo-1, 3-dihydro-isoindol-2-yl)-ethyl]-phenyl ester The title compound was prepared in 39% yield as an oil using methyl-phenyl-carbamic acid 4- (2-hydroxy-ethyl)-phenyl ester and isoindole-1, 3-dione. NMR (400MHz ; CDCI3) : a 2.98 (t, 2H), 3.41 (br s, 2H), 3.89 (t, 3H), 7.04 (br d, 2H), 7.20-7. 40 (m, 7H), 7.68-7. 71 (m, 2H), 7.80- 7.83 (m, 2H); HPLC-MS: m/z = 401.1 (M+1); Rt = 4.41 min.

Example 601 4-Phenyl-piperidine-1-carboxylic acid 4- (5-methyl-pyridin-2-ylmethyl)-phenyl ester To a solution of 4- (5-methyl-pyridin-2-ylmethyl) phenol (0.8 mmol) prepared as described above and ethyidiisopropylamine (1.5 mmol) in CH2CI2 (5 mL) at-30 °C was added trichlor- methyl chloroformiate (1.0 mmol). The solution was stirred at-30 °C for 10 min and at reflux

temperature for 2 h. The solution was evaporated to dryness and redissolved in CH2CI2 (5 mL) and cooled to 0 °C before addition of 4-phenylpiperidine (1.5 mmol). The solution was stirred at room temperature for 16 h evaporated to give the crude product which was purified by FC (Quad flash 40 CH2CI2 : Et2O : Heptane : Et3N 1: 1: 2: 0.25->1 : 1: 1: 0.25) to give the title compound in 28% yield as an oil.

1H NMR (400MHz ; CDCI3) : 81. 70-1.80 (m, 2H), 1.91 (brd, 2H), 2.29 (s, 3H), 2.72 (tt, 1H), 2.94 (brt, 1H), 3.08 (brt, 1H), 4.10 (s, 2H), 4.42 (brs, 1H), 7.00 (d, 1H), 7.06 (d, 2H), 7.21- 7.26 (m, 5H), 7.32 (d, 2H), 7.38 (dd, 1 H), 8.37 (d, 1 H) ; HPLC-MS: m/z = 387.2 (M+1); Rt = 2.95 min.

Example 602 4- (4-Methoxy-phenyl)-3, 6-dihydro-2H-pyridine-1-carboxylic acid 4- (5-methyl-pyridin-2- ylmethyl)-phenyl ester To a solution of 4- (5-methyl-pyridin-2-ylmethyl) phenol (0.8 mmol) prepared as described above and ethyidiisopropylamine (1.5 mmol) in CH2CI2 (5 mL) at-30 °C was added trichlor- methyl chloroformiate (1.0 mmol). The solution was stirred at-30 °C for 10 min and at reflux temperature for 2 h. The solution was evaporated to dryness and redissolved in CH2C12 (5 mL) and cooled to 0 °C before addition of 4- (4-methoxyphenyl)-1, 2,3, 6-tetrahydro-pyridine (1.5 mmol). The solution was stirred at room temperature for 16 h evaporated to give the crude product which was purified by FC (Quad flash 40 CH2CI2 : Et2O : Heptane : Et3N 1: 1: 2: 0.25 ->1 : 1: 1: 0.25) to give the title compound in 10% yield as colorless crystals.

'H NMR (400MHz ; CDC13) : 52. 30 (s, 3H), 2.60 (br s, 2H), 3.75-3. 88 (m, 5H), 4.12 (s, 2H), 4.20 (br s, 1 H), 4.30 (br s, 1 H), 5.98 (br s, 1 H), 6.88 (d, 2H), 7.00 (d, 1 H), 7.07 (d, 2H), 7.24 (d, 2H), 7.34 (d, 2H), 7.39 (dd, 1 H), 8.38 (d, 1 H) ; HPLC-MS: m/z = 415.3 (M+1) ; Rt = 2.95 min.

PHARMACOLOGICAL METHODS Compounds of formula I may be evaluated in vitro for their efficacy and potency to inhibit HSL, and such evaluation may be performed as described below.

ASSAYS Hormone-sensitive lipase (HSL) Materials. The Hormone-sensitive lipase was provided by Dr. Cecilia Holm, from Lund Uni- versity Sweden or produced and purified by Novo Nordisk (NN) using the reagents and pro- tocols used by Dr. Holm. The substrates used are: 3H-labeled triolen (TO) from Amersham, Buckinghamshire, U. K. cat No. TRA191 ; 5-20 Ci/mmol dissolved in toluene, triolen (Sigma, Cat. No. T-1740), fluorochrome-labeled triacylglyceride (cis-octadec-9-enoic acid 2- [12- (7- nitrobenzo [1,2, 5] oxadiazol-4-ylamino) dodecanoyloxy]-1-cis-octadec-9-enoyloxymethyl-ethyl ester) prepared by Novo Nordisk (NN) by conventional methods, and 1, 3-(di [3H]-stearin), 2- (PEG-Biotin) glycerol prepared in collaboration with Amersham Pharmacia Biotech, UK and described in WO 01/073442. Phosphatidyl choline (PC) and phosphatidyl inositol (PI) are from Sigma (St Luis MO cat. Nos. P-3556 and P-5954 respectively). All other reagents are of commercial grade and obtained from various commercial sources.

Methods.

3180.1 : Assay for determination of inhibitor ICgo values.

A lipid emulsion with 3H-Triolein and phospholipid is used as substrate with a standard cencentration of highly purified HSL. BSA is added as product receptor. The substrate is prepared as follows : 30 ul PC: PI (20 mg/ml solution of PC: PI 3: 1 prepared in chloroform) + 128 NI cold TO + 15 psi 3H-TO are mixed and then evaporated under a gentle stream of N2 followed by 20-30 min- utes in a Speedvac to ensure the absence of residual solvent.

Compound and HSL are incubated for 30 min at 25 °C before addition of substrate. Reaction is stopped after 30 min at 25 °C by adding a mixture of methanol, chloroform and heptane at high pH. Formed product is separated from substrate by phase separation.

Standard concentrations of compound are 100, uM, 20, uM, 4, uM, 0. 8, uM, 0. 16, uM and 0. 032liM (sample concentrations).

Results are given as IC50 values after 4PL fit of obtained activity data.

3180.2 : Assay for determination of percent inhibition by compound at 10 uM concentration.

A lipid emulsion with 3H-Triolein and phospholipid is used as substrate with a standard cencentration of highly purified HSL. BSA is added as product receptor. The substrate is prepared as follows : 30 ul PC: PI (20 mg/ml solution of PC: PI 3: 1 prepared in chloroform) + 128 ul cold TO + 15 ul 3H-TO are mixed and then evaporated under a gentle stream of N2 followed by 20-30 min- utes in a Speedvac to ensure the absence of residual solvent.

Compound and HSL are incubated for 30 min at 25 °C before addition of substrate. Reaction is stopped after 30 min at 25 °C by adding a mixture of methanol, chloroform and heptane at high pH. Formed product is separated from substrate by phase separation.

Results are given as percent activity relative to an un-inhibited sample (no compound).

3190.1 : Assay for determination of percent inhibition of hormone sensitive lipase by com- pound at 10uM sample concentration.

A lipid emulsion with fluorochrome-labeled triacylglyceride and phospholipid is used as sub- strate with a standard concentration of highly purified HSL (12ug/mL initial concentration cor- responding to 600ng/mL final concentration). BSA is added as product receptor. The transfer of the fluorochrome from the lipid phase to the water (BSA) phase changes the fluorescent properties of the fluorochrome. The changes can be monitored on a fluorimeter with an exci- tation wavelength of 450nm and an emission wavelength of 545nm.

Compound and HSL (20pL compound, 10uL enzyme and 70uL PED-BSA buffer) is pre- incubated for 30min at 25°C before addition of substrate (100uL). Amount of formed product is measured after 120min incubation at 37°C.

Results are given as percent activity relative to a non-inhibited sample (no compound).

3190.2 : Assay for determination of IC5o value for the inhibition of hormone sensitive lipase by compound. Standard concentrations of compound are 100, uM and 5-fold dilutions (initial con- centration corresponding to 10, uM final concentration and 5-fold).

A lipid emulsion with fluorochrome-labeled triacylglyceride and phospholipid is used as sub- strate with a standard concentration of highly purified HSL (12ug/mL initial concentration cor- responding to 600ng/mL final concentration). BSA is added as product receptor. The transfer of the fluorochrome from the lipid phase to the water (BSA) phase changes the fluorescent

properties of the fluorochrome. The changes can be monitored on a fluorimeter with an exci- tation wavelength of 450nm and an emission wavelength of 545nm.

Compound and HSL (20pL compound, 10uL enzyme and 70uL PED-BSA buffer) is pre- incubated for 30min at 25°C before addition of substrate (100uL). Amount of formed product is measured after 120min incubation at 37°C.

Results are given as IC50 values after 4PL fit of obtained activity data.

2848.2 : This high-volume screening assay uses para-nitrophenyl butyrate (p-NPB) as sub- strate for HSL. HSL cleaves p-NPB and the reaction is monitored as an increase in the con- centration of para-nitrophenol (p-NP). p-NP can be monitored as an increase in UV- absorbance at 405 nm. The reaction is carried out at room-temp. for 20 min. The action is not stopped, but instead UV-abs is measured at a fixed time (20 min. ) Due to autohydrolysis of the substrate the reaction is read at t = 0 min. too and t = 20 min. and the increase in Abs is calculated as the difference between the two readings. When a compound that inhibits HSL is present, it results in a relative decrease in UV-absorbance.

% Eff (% Inhibition) = (S-SOEff)/ (SmaxEff-SOEff) x 100 Where S = signal in UV-abs. , SOEff = assaybuffer alone, SmaxEff = Assaybuffer with the li- pase inhibitor.

2898.2 : This method is an enzyme assay based upon SPA (scintillation proximity assay) par- ticles. The substrate, 1, 3-(di-[3H]-stearin), 2-(PEG-Biotin)-glycerol, is marked with 3H in both fatty acid moieties in the tri-glyceride. The third moiety of the tri-glyceride is a PEG linked Biotin. The substrate binds through Biotin to streptavidin in the SPA particles and the prox- imity between the radioactive tritium in the stearic acid moiety and the SPA particle results in emission of light from the SPA particles. The assay is an on-bead assay where HSL de- grades the substrate, where after 3H-stearin acid is released from the bead. The amount of light emitted is proportional to the amount of substrate bound to the receptor. When a com- pound that inhibits the activity of HSL is present it results in a decrease in degradation of the substrate and thus an increase in the amount of light emitted and a concomitant increase in % Eff.

% Eff (% Inhibition) = (S-SOEff)/ (SmaxEff-SOEff) x 100 Where S = signal in dpm. , SOEff = no inhibitor added, SmaxEff = with maximum concentra- tion of inhibitor.

RESULTS With these methods the following results were obtained for the compounds of the examples. Compound Test 3190.1 Test 3180.2 Test 2898.2 Test 2848. 2 according HSL_FL HSL HSL-2 HSL to example % ACTIVITY % ACTIVITY % Inhibition % Inhibition All All All All 120 40 122 14 123 22 121 24 118 24 119 10 47 42 46 43 11 17 87 48 81 36 48 15 61 23 6 49 85 88 90 24 54 52 62 88 59 16 24 30 20 51 92 62 73 39 109 15. 9 106 23. 8 108 37. 2 114 42. 4 126 33 110 18. 8 111 36.2 107 59. 9 105 26. 8 104 19. 8 127 58. 7 128 33. 8 103 2 101. 4 115 85 73. 6 113 18. 3 129 27 112 86 116 23. 5 124 75.1 117 2 130 30.1 131 21.6 32 19. 6 133 15. 8 144 25