Title:
IMIDAZOLE COMPOUNDS AS HISTAMINE H3 LIGANDS
Document Type and Number:
WIPO Patent Application WO/2000/053596
Kind Code:
A2
Abstract:
This invention discloses a compound having general formula depicted in Formula (I), wherein G is a spacer moiety selected from the group consisting of C¿1?-C¿7? alkyl, C¿2?-C¿7? alkenyl, C¿2?-C¿7? alkynyl, C¿1?-C¿7? alkyl-NHCO-, and -SO2-, T is a six-membered ring or a seven-membered ring containing two ring nitrogens and belonging to formula (a), with said T ring being c onnected to said G moiety at either a ring carbon atom of ring T or a ring nitrogen atom of ring T: wherein n is 1 or 2. These compounds have excellent histamine-H¿3? receptor antagonist activity.
Inventors:
VACCARO WAYNE D
PIWINSKI JOHN J
TOM WING C
SOLOMON DANIEL M
ASLANIAN ROBERT G
PIWINSKI JOHN J
TOM WING C
SOLOMON DANIEL M
ASLANIAN ROBERT G
Application Number:
PCT/US2000/005897
Publication Date:
September 14, 2000
Filing Date:
March 06, 2000
Export Citation:
Assignee:
SCHERING CORP (US)
International Classes:
A61K31/496; A61K45/00; A61P1/06; A61P9/12; A61P11/04; A61P25/06; A61P25/18; A61P25/20; C07D233/64; A61P25/28; A61P27/06; A61P29/00; A61P37/08; A61P43/00; C07D233/54; C07D401/12; C07D401/14; C07D403/06; C07D403/12; C07D403/14; (IPC1-7): C07D403/06; A61K31/50; A61P43/00; C07D403/12; C07D233/54; C07D401/12; C07D401/14; C07D403/14
Domestic Patent References:
| WO1996030343A1 | 1996-10-03 | |||
| WO1993012093A1 | 1993-06-24 | |||
| WO1993012107A1 | 1993-06-24 |
Attorney, Agent or Firm:
Kalyanaraman, Palaiyur S. (K-6-1 1990 2000 Galloping Hill Road Kenilworth, NJ, US)
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Claims:
CLAIMS What is claimed is:
| 1. | A compound having the general formula depicted in Formula I, including enantiomers, stereoisomers and tautomers thereof, as well as pharmaceutically acceptable salts or solvates of said compounds: Formula I wherein G is a spacer moiety selected from the group consisting of C1 C7 alkyl, C2C7 alkenyl, C2C7 alkynyl, C1C7 alkylNHCO, andS02, with said alkyl, alkenyl or alkynyl being optionally substituted with one or more groups selected from substituted or unsubstituted alkyl, aryl, aralkyl, alkylaryl,Oalkyl, andCO2alkyl, and wherein said substituents are selected from the group consisting of alkyl, aryl, aralkyl, and halogen; and T is a sixmembered ring or a sevenmembered ring containing two ring nitrogens and belonging to the formula a shown below, with said T ring being connected to said G moiety at either a ring carbon atom of ring T or a ring nitrogen atom of ring T: wherein n is 1 or 2; and R2, R3, R4, R5, R6 and R7 can be the same or different with the proviso that no two of said R3, R4, R5 and R6 are bound to the same carbon <BR> <BR> <BR> <BR> <BR> atom of ring T except when at least one of said R3, R4, R5 and R6 is H, wherein said R2, and R7 are independently selected from the group consisting of H, substituted or unsubstituted C1C6 alkyl, substituted or unsubstituted C2C6 alkenyl, substituted or unsubstituted C2C6 alkynyl, aryl, aralkyl, alkylaryl,C (=O) Rg,C02Rg,SO2Rg, S (O) Rg, C (O) NRgR9,C (=NR8) NRgR9, and said R3, R4, R5, and R6 can be the same or different and are independently selected from the group consisting of H, substituted or unsubstituted C1C6 alkyl, substituted or unsubstituted C2C6 alkenyl, substituted or unsubstituted C2C6 alkynyl, aryl, aralkyl, alkylaryl, C (=O) R8,C02R8,S02R8, S (O) Rg,C (O) NRgR9,C (=NR8) NRgR9 CORg,OC (O) R8,NR8R9,SR8,OH,OR8,CH20R8,CH2N (R8) 2, CH2SRg,NRg (CO) NRgR9,CX (Rg) 2,CX2Rg,CX3,OCX3,N (Rg) S (O) R9,N (Rg)S02R9, (=O), (=NORg),NRgS02NRgR9,SO3H, and PO3H2 wherein R8 and Rg are independently H or substituted or unsubstituted C1C6 alkyl, substituted or unsubstituted aryl, substituted or unsubstituted aralkyl, or substituted or unsubstituted alkylaryl, substituted or unsubstituted alkenylaryl, substituted or unsubstituted alkenylheteroaryl and X is a halogen, further wherein when the spacer moiety G is linked to a ring <BR> <BR> <BR> <BR> nitrogen atom of ring T then one of said R2 or Ry is absent on the ring<BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> nitrogen atom linked to the G moiety, and the other of said R2 or R7 is present on the ring nitrogen atom that is not linked to the G moiety, and still further wherein when G is a C1C7 alkyl and is linked to a ring nitrogen of ring T, then said R2 or R7 on the other ring nitrogen of ring T is not hydrogen, substituted or unsubstituted C1C6 alkyl or substituted or unsubstituted C2C6 alkenyl or aryl. |
| 2. | The compound of Claim 1 having the formula: wherein the symbols are as defined in Claim 1. |
| 3. | The compound of Claim 1 having the formula: wherein the symbols are as defined in Claim 1. |
| 4. | The compound of Claim 2, wherein G is C1C6 alkyl or C1C7 alkylNHCOand R2 is H. |
| 5. | The compound of Claim 3, wherein R2 isC (=O) Rg,CO2Rg, cr C (O) NRgR9. |
| 6. | The compound of Claim 2, wherein R2 is selected from the group consisting of H, substituted or unsubstituted ClC6 alkyl, substituted or unsubstituted C2C6 alkenyl, substituted or unsubstituted C2C6 alkynyl, aryl, aralkyl, alkylaryl,C (=O) Rg,CO2Rg, S02Rg, S (O) R8,C (O) NRgR9,C (=NRg) NRgR9. |
| 7. | A compound selected from the group consisting of the molecules represented by the following chemical structures:. |
| 8. | A pharmaceutical composition comprising as an active ingredient a compound of Claim 1. |
| 9. | A pharmaceutical composition, for use in treating allergy, inflammation, hypertension, glaucoma, sleeping disorders, states of hyperand hypomotility of the gastrointestinal tract, hypoand hyperactivity of the central nervous system, Alzheimer's disease, schizophrenia, and migraines, comprising a pharmaceutically acceptable carrier and an effective amount of a Compound of Claim 1. |
| 10. | A method of treating allergy, inflammation, hypertension, glaucoma, sleeping disorders, states of hyperand hypomotility of the gastrointestinal tract, hypoand hyperactivity of the central nervous system, Alzheimer's disease, schizophrenia, and migraines comprising administering an effective amount of a compound of Claim 1 to a patient in need of such treatment. |
| 11. | The use of a compound of Claim 1 for the manufacture of a medicament for use in treating allergy, inflammation, hypertension, glaucoma, sleeping disorders, states of hyperand hypomotility of the gastrointestinal tract, hypoand hyperactivity of the central nervous system, Alzheimer's disease, schizophrenia, and migraines. |
| 12. | The use of a compound of Claim 1 for the treatment of allergy, inflammation, hypertension, glaucoma, sleeping disorders, states of hyperand hypomotility of the gastrointestinal tract, hypoand hyperactivity of the central nervous system, Alzheimer's disease, schizophrenia, and migraines. |
| 13. | The use of a compound of Claim 1 in combination with a histamine H1 receptor antagonist for treating upper airway allergic responses. |
| 14. | A method of preparing a pharmaceutical composition comprising admixing a compound of Claim 1 with a pharmaceutically acceptable carrier. |
| 15. | The method of Claim 14, wherein said pharmaceutical composition additionally comprises an antihistaminic effective amount of a histamine H1 receptor antagonist. |
| 16. | A pharmaceutical composition comprising as an active ingredient a compound of Claim 7. |
| 17. | A pharmaceutical composition, for use in treating allergy, inflammation, hypertension, glaucoma, sleeping disorders, states of hyperand hypomotility of the gastrointestinal tract, hypoand hyperactivity of the central nervous system, Alzheimer's disease, schizophrenia, and migraines, comprising a pharmaceutically acceptable carrier and an effective amount of a compound of Claim 7. |
| 18. | A method of treating allergy, inflammation, hypertension, glaucoma, sleeping disorders, states of hyper and hypomotility of the gastrointestinal tract, hypoand hyperactivity of the central nervous system, Alzheimer's disease, schizophrenia, and migraines comprising administering an effective amount of a compound of Claim 7 to a patient in need of such treatment. |
| 19. | The use of a compound of Claim 7 in combination with a histamine H1 receptor antagonist for treating upper airway allergic responses. |
Description:
INTERNATIONALSEARCHREPORT m nal Appilcathn bb IMaxalApplleatlonNo , nformathn on p t nttamily members PCT/US 00/05897 PatentdocumentPublication Patent citedinsearchreportdate member(s)date WO9630343A03-10-1996US 5856326 A 05-01-1999 AU 710672 B 23-09-1999 AU 5322396 A 16-10-1996 BG 101973 A 29-05-1998 BR 9607953 A 14-07-1998 CA 2216707 A 03-10-1996 CN 1195340 A 07-10-1998 CZ 9703062 A 18-03-1998 EP 0820445 A 28-01-1998 HR 960143 A 30-04-1998 HU 9801883 A 28-06-1999 JP 3043815 B 22-05-2000 JP 10511098 T 27-10-1998 NO 974457 A 28-11-1997 NZ 305254 A 29-03-1999 PL 322549 A 02-02-1998 SK 129297 A 06-05-1998 ZA 9602433 A 02-10-1996 WO9312093A24-06-1993AT 128708 T 15-10-1995 AU 662588 B 07-09-1995 AU 3247793 A 19-07-1993 CA 2125964 A 24-06-1993 DE 69205287 D 09-11-1995 DE 69205287 T 14-03-1996 DK 618905 T 04-12-1995 EP 0618905 A 12-10-1994 ES 2078118 T 01-12-1995 GR 3018474 T 31-03-1996 HK 185696 A 11-10-1996 IL 104126 A 09-05-1999 JP 2540015 B 02-10-1996 JP 6511251 T 15-12-1994 KR 136207 B 25-04-1998 NZ 246295 A 25-06-1996 US 5633250 A 27-05-1997 ZA 9209786 A 18-06-1993 WO9312107A24-06-1993AT 140223 T 15-07-1996 AU 665604 B 11-01-1996 AU 3275893 A 19-07-1993 CA 2126086 A 24-06-1993 DE 69212164 D 14-08-1996 DE 69212164 T 05-12-1996 DK 619818 T 25-11-1996 EP 0619818 A 19-10-1994 ES 2089782 T 01-10-1996 GR 3021195 T 31-12-1996 HK 31097 A 21-03-1997 IL 104124 A 06-12-1998 JP 7121938 B 25-12-1995 JP 6511252 T 15-12-1994 KR 142801 B 15-07-1998 MX 9207392 A 01-06-1993 NZ 246434 A 27-02-1996 SG 44565 A 19-12-1997 US 5932596 A 03-08-1999 ZA 9209785 A 21-06-1993
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