HETEROCYCLIC COMPOUNDS AS DGAT1 INHIBITORS

Title:

HETEROCYCLIC COMPOUNDS AS DGAT1 INHIBITORS

Document Type and Number:

WIPO Patent Application WO/2012/029032

Kind Code:

Abstract:

The present invention relates to heterocyclic compounds of formula 1, in all their stereoisomeric and tautomeric forms; and their pharmaceutically acceptable salts, solvates, polymorphs, prodrugs, carboxylic acid isosteres and N-oxides. The invention also relates to processes for the manufacture of the heterocyclic compounds and to pharmaceutical compositions containing them. The said compounds and their pharmaceutical compositions are useful in the prevention and treatment of diseases or disorders mediated by diacylglycerol acyltransferase (DGAT), particularly DGAT1. The present invention further provides a method of treatment of such diseases or disorders by administering a therapeutically effective amount of said compounds or their pharmaceutical compositions, to a mammal in need thereof.

Inventors:

SHARMA RAJIV (IN)
KADAM KISHORKUMAR SHIVAJIRAO (IN)
JADHAV RAVINDRA DNYANDEV (IN)
KANDRE SHIVAJI SADASHIV (IN)
GUPTE AMOL (IN)

Application Number:

PCT/IB2011/053810

Publication Date:

March 08, 2012

Filing Date:

August 31, 2011

Export Citation:

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Assignee:

PIRAMAL LIFE SCIENCES LTD (IN)
SHARMA RAJIV (IN)
KADAM KISHORKUMAR SHIVAJIRAO (IN)
JADHAV RAVINDRA DNYANDEV (IN)
KANDRE SHIVAJI SADASHIV (IN)
GUPTE AMOL (IN)

International Classes:

C07D231/12

Domestic Patent References:

WO2007016538A2

2007-02-08

Foreign References:

JP2008255024A	2008-10-23
US7625914B2	2009-12-01
US4699915A	1987-10-13
EP2103603A1	2009-09-23
US20090093516A1	2009-04-09
US4812470A	1989-03-14

Other References:

EXPERT OPIN. THER. TARGETS, vol. 13, no. 2, 2009, pages 195 - 207
NATURE GENETICS, vol. 25, 2000, pages 87 - 90
THE JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 284, no. 7, 2009, pages 4292 - 4299
EXPERT OPIN. THER. TARGETS, vol. 10, no. 5, 2006, pages 749 - 757
CAMILLE G. WERMUTH: "The Practice of Medicinal Chemistry, Second Edition,", 2003, pages: 189 - 214
JOURNAL OF MEDICINAL CHEMISTRY, vol. 47, 2004, pages 6764
LEO A. PAQUETTE: "Chiral reagents for Asymmetric Synthesis", JOHN WILEY & SONS LTD.
GRAHAM. L. PATRICK,: "An introduction to Medicinal Chemistry, Second Edition", OXFORD UNIVERSITY PRESS, pages: 239 - 248
VALENTINO J. STELLA, RENALD T. BORCHARDT, MICHAEL J. HAGEMON, REZA OLIYAI, HANS MAAG, JEFFERSON W. TILLEY: "Prodrugs: Challenges and Rewards", AAPS PRESS
JOURNAL OF MEDICINAL CHEMISTRY, ENG, vol. 47, no. 9, 2004, pages 2318 - 25

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Claims:

We claim:

1 . A compound of formula 1 :

Formula 1

or a stereoisomer, tautomer, pharmaceutically acceptable salt, solvate or N-oxide thereof;

wherein,

Z is selected from:

indicates the point of attachment;

n is an integer selected from 1 -5;

m is 0 or 1 ;

Ri and R₂ are independently selected from hydrogen or (CrCi₂)-alkyl, or R! and R₂ can optionally form an unsubstituted or substituted (C₃-C₇) cycloalkyi ring;

R₃ is hydrogen or (CrCi₂)-alkyl;

R₅ is selected from hydrogen, (Ci-Ci₂)-alkyl, CF₃, (C₃-C₇)-cycloalkyl, aryl, or heterocyclyl; B is a 5-membered heteroaryl ring represented by any one of the general structures (i) to (x);

wherein 1 and 2 are the points of attachment of B to phenyl and to Z respectively and R₄ is selected from hydrogen, (CrCi₂)-alkyl or aryl; or B is a 6-membered heteroaryl ring containing 1 or 2 N-atoms, wherein the 6-membered heteroaryl ring may be unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (CrCi₂)-alkoxy, cyano, nitro, (CrCi₂)-alkyl, (C₂-Ci₂)-alkenyl, (C₂-Ci₂)-alkynyl, (C₃-Ci₂)- cycloalkyl, aryl, aryloxy, heterocyclyl or O-heterocyclyl;

L is selected from ^*NHC(0)NH, ^*N(CH₃)C(0)NH ^*NHC(S)NH, ^*S0₂NH, ^*CONH or ^*NH(C=NR₆)NH, wherein ^* indicates the point of attachment of L to A, and R₆ is selected from hydrogen, methyl, cyano or nitro;

A is selected from (C Ci₂)-alkyl, (C₃-Ci₂)-cycloalkyl, aryl or heterocyclyl; wherein,

(Ci-Ci₂)-alkyl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (Ci-Ci₂)-alkoxy, cyano, nitro, (C₃-Ci₂)-cycloalkyl, aryl, heterocyclyl, C(0)R_p, C(0)OR_p, NRpRq, C(0)NR_pR_q, SR_P, S(0)R_p or S0₂R_p;

(C₃-Ci₂)-cycloalkyl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (Ci-Ci₂)-alkoxy, cyano, nitro, aryl, heterocyclyl, C(0)R_p, C(0)OR_p, NR_pRq, C(0)NR_pR_q, SR_P, S(0)R_p or S0₂R_p;

aryl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (Ci-Ci₂)-alkoxy, cyano, nitro, (Ci-Ci₂)-alkyl, OCF₃, CF₃, (C₂-Ci₂)-alkenyl, (C₂- Ci₂)-alkynyl, (C₃-Ci₂)-cycloalkyl, aryl, aryloxy, heterocyclyl, O-heterocyclyl, C(0)R_p, C(0)OR_p, NR_pRq, C(0)NR_pR_q, SR_P, S(0)R_p or S0₂R_p; or aryl may be fused with an unsubstituted or substituted 5 or 6-membered cycloalkyi ring optionally containing one or more heteroatoms selected from O, N or S;

heterocyclyl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (CrCi₂)-alkoxy, cyano, nitro, (CrCi₂)-alkyl, (C₂-Ci₂)-alkenyl, (C₂- Ci₂)-alkynyl, (C₃-Ci₂)-cycloalkyl, aryl, aryloxy, heterocyclyl, O-heterocyclyl, C(0)R_p, C(0)OR_p, NRpRq, C(0)NRpR_q, SR_P, S(0)R_p or S0₂R_p;

R_p and R_q are independently selected from hydrogen, (Ci-Ci₂)-alkyl, aryl, aralkyi or heterocyclyl, or R_p and R_q together with the N to which they are attached optionally form a 3 to 7 membered ring;

with a proviso that A is not a methyl group.

2. The compound of formula 1 according to claim 1 , represented by a compound of formula 1 a;

Formula 1 a

or a stereoisomer, tautomer, pharmaceutically acceptable salt, solvate or N-oxide thereof;

wherein,

Z is selected from:

indicates the point of attachment;

n is an integer selected from 1 -5;

m is 0 or 1 ;

Ri and R₂ are independently selected from hydrogen or (CrCi₂)-alkyl, or R! and R₂ can optionally form an unsubstituted or substituted (C₃-C₇) cycloalkyl ring;

R₃ is hydrogen or (CrCi₂)-alkyl;

R₅ is selected from hydrogen, (Ci-Ci₂)-alkyl, CF₃, (C₃-C₇)-cycloalkyl, aryl, or heterocyclyl;

B is a 5-membered heteroaryl ring represented by any one of the general structures (i) to (x);

(Ci-Ci₂)-alkoxy, cyano, nitro, (Ci-Ci₂)-alkyl, (C₂-Ci₂)-alkenyl, (C₂-Ci₂)-alkynyl, (C₃-Ci₂)- cycloalkyl, aryl, aryloxy, heterocyclyl or O-heterocyclyl;

L is selected from ^*NHC(0)NH, ^*N(CH₃)C(0)NH ^*NHC(S)NH, ^*S0₂NH, ^*CONH or

^*NH(C=NR₆)NH, wherein ^* indicates the point of attachment of L to A, and R₆ is selected from hydrogen, methyl, cyano or nitro; A is selected from (CrCi₂)-alkyl, (C₃-Ci₂)-cycloalkyl, aryl or heterocyclyl; wherein,

(CrCi₂)-alkyl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (CrCi₂)-alkoxy, cyano, nitro, (C₃-Ci₂)-cycloalkyl, aryl, heterocyclyl, C(0)R_p, C(0)OR_p, NRpRq, C(0)NR_pR_q, SR_P, S(0)R_p or S0₂R_p;

aryl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (Ci-Ci₂)-alkoxy, cyano, nitro, (Ci-Ci₂)-alkyl, OCF₃, CF₃, (C₂-Ci₂)-alkenyl, (C₂- Ci₂)-alkynyl, (C₃-Ci₂)-cycloalkyl, aryl, aryloxy, heterocyclyl, O-heterocyclyl, C(0)R_p, C(0)OR_p, NRpR_q, C(0)NRpR_q, SR_P, S(0)R_p or S0₂R_p; or aryl may be fused with an unsubstituted or substituted 5 or 6-membered cycloalkyl ring optionally containing one or more heteroatoms selected from O, N or S;

with a proviso that A is not a methyl group. 3. The compound of formula 1 according to claim 2;

wherein,

B is

wherein 1 and 2 are the points of attachment of B to phenyl and to Z respectively;

Z is

indicates the point of attachment;

n is an integer selected from 1 -5;

m is 0 or 1 ;

Ri and R₂ are independently selected from hydrogen or (CrCi₂)-alkyl, or and R₂ can optionally form an unsubstituted or substituted (C₃-C₇) cycloalkyl ring;

R₃ is hydrogen or (CrCi₂)-alkyl;

R₅ is selected from hydrogen, (Ci-Ci₂)-alkyl, CF₃, (C₃-C₇)-cycloalkyl, aryl, and heterocyclyl; and

A is selected from (C Ci₂)-alkyl, (C₃-Ci₂)-cycloalkyl, aryl or heterocyclyl; wherein,

(Ci-Ci₂)-alkyl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (Ci-Ci₂)-alkoxy, cyano, (C₃-Ci₂)-cycloalkyl, aryl or heterocyclyl;

(C₃-Ci₂)-cycloalkyl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (C Ci₂)-alkoxy, cyano, aryl and heterocyclyl;

aryl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (Ci-Ci₂)-alkoxy, cyano, (Ci-Ci₂)-alkyl, OCF₃, CF₃, (C₃-Ci₂)-cycloalkyl, aryl, aryloxy, heterocyclyl or O-heterocyclyl, or aryl may be fused with an unsubstituted or substituted 5 or 6-membered cycloalkyi ring optionally containing one or more heteroatoms selected from O, N or S;

heterocyclyl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (CrCi₂)-alkoxy, cyano, (CrCi₂)-alkyl, (C₃-Ci₂)-cycloalkyl, aryl, aryloxy, heterocyclyl or O-heterocyclyl;

with the proviso that A is not a methyl group.

4. The compound of formula 1 according to claim 2;

wherein,

B is

wherein 1 and 2 are the points of attachment of B to phenyl and to Z respectively;

Z is selected from:

— - indicates the point of attachment;

n is an integer selected from 1 -5;

m is 0 or 1 ; Ri and R₂ are independently selected from hydrogen or (CrCi₂)-alkyl, or R! and R₂ can optionally form an unsubstituted or substituted (C₃-C₇) cycloalkyi ring;

R₃ is hydrogen or (CrCi₂)-alkyl;

R₅ is selected from hydrogen, (Ci-Ci₂)-alkyl, CF₃, (C₃-C₇)-cycloalkyl, aryl, or heterocyclyl; and

A is selected from (Ci-Ci₂)-alkyl, (C₃-Ci₂)-cycloalkyl, aryl or heterocyclyl; wherein,

(Ci-Ci₂)-alkyl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (Ci-Ci₂)-alkoxy, cyano, (C₃-Ci₂)-cycloalkyl, aryl or heterocyclyl;

(C₃-Ci₂)-cycloalkyl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (C Ci₂)-alkoxy, cyano, aryl or heterocyclyl;

aryl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (Ci-Ci₂)-alkoxy, cyano, (Ci-Ci₂)-alkyl, OCF₃, CF₃, (C₃-Ci₂)-cycloalkyl, aryl, aryloxy, heterocyclyl or O-heterocyclyl; or aryl may be fused with an unsubstituted or substituted 5 or 6-membered cycloalkyi ring optionally containing one or more heteroatoms selected from O, N or S;

heterocyclyl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (C Ci₂)-alkoxy, cyano, (Ci-Ci₂)-alkyl, (C₃-Ci₂)-cycloalkyl, aryl, aryloxy, heterocyclyl or O-heterocyclyl;

with the proviso that A is not a methyl group.

5. The compound of formula 1 according to claim 2;

wherein,

B is

wherein 1 and 2 are the points of attachment of B to phenyl and to Z respectively;

Z is selected from:

— - indicates the point of attachment;

n is an integer selected from 1 -5;

m is 0 or 1 ;

Ri and R₂ are independently selected from hydrogen or (CrCi₂)-alkyl, or and R₂ can optionally form an unsubstituted or substituted (C₃-C₇) cycloalkyl ring;

R₃ is hydrogen or (CrCi₂)-alkyl;

R₅ is selected from hydrogen, (Ci-Ci₂)-alkyl, CF₃, (C₃-C₇)-cycloalkyl, aryl, or heterocyclyl; and

A is selected from (C Ci₂)-alkyl, (C₃-Ci₂)-cycloalkyl, aryl or heterocyclyl; wherein,

(Ci-Ci₂)-alkyl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (Ci-Ci₂)-alkoxy, cyano, (C₃-Ci₂)-cycloalkyl, aryl or heterocyclyl;

(C₃-Ci₂)-cycloalkyl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (C Ci₂)-alkoxy, cyano, aryl or heterocyclyl;

aryl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (Ci-Ci₂)-alkoxy, cyano, (Ci-Ci₂)-alkyl, OCF₃, CF₃, (C₃-Ci₂)-cycloalkyl, aryl, aryloxy, heterocyclyl or O-heterocyclyl; or aryl may be fused with an unsubstituted or substituted 5 or 6-membered cycloalkyi ring optionally containing one or more heteroatoms selected from O, N or S;

with the proviso that A is not a methyl group.

6. The compound of formula 1 according to claim 2,

wherein,

B is

wherein 1 and 2 are the points of attachment of B to phenyl and to Z respectively; Z is selected from:

indicates the point of attachment;

n is an integer selected from 1 -5;

m is 0 or 1 ; Ri and R₂ are independently selected from hydrogen or (CrCi₂)-alkyl, or R! and R₂ can optionally form an unsubstituted or substituted (C₃-C₇) cycloalkyi ring;

R₃ is hydrogen or (CrCi₂)-alkyl;

R₅ is selected from hydrogen, (Ci-Ci₂)-alkyl, CF₃, (C₃-C₇)-cycloalkyl, aryl, or heterocyclyl; and

A is selected from (Ci-Ci₂)-alkyl, (C₃-Ci₂)-cycloalkyl, aryl or heterocyclyl; wherein,

(Ci-Ci₂)-alkyl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (Ci-Ci₂)-alkoxy, cyano, (C₃-Ci₂)-cycloalkyl, aryl or heterocyclyl;

(C₃-Ci₂)-cycloalkyl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (C Ci₂)-alkoxy, cyano, aryl or heterocyclyl;

aryl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (Ci-Ci₂)-alkoxy, cyano, (Ci-Ci₂)-alkyl, OCF₃, CF₃, (C₃-Ci₂)-cycloalkyl, aryl, aryloxy, heterocyclyl or O-heterocyclyl; or aryl may be fused with an unsubstituted or substituted 5 or 6-membered cycloalkyi ring optionally containing one or more heteroatoms selected from O, N or S;

with the proviso that A is not a methyl group.

7. The compound of formula 1 according to claim 1 , represented by a compound of formula 1 b,

Formula 1 b

or a stereoisomer, tautomer, pharmaceutically acceptable salt, solvate or N-oxide thereof;

wherein,

Z is selected from:

indicates the point of attachment;

n is an integer selected from 1 -5;

m is 0 or 1 ;

Ri and R₂ are independently selected from hydrogen or (CrCi₂)-alkyl, or R! and R₂ can optionally form an unsubstituted or substituted (C₃-C₇) cycloalkyi ring;

R₃ is hydrogen or (CrCi₂)-alkyl;

R₅ is selected from hydrogen, (Ci-Ci₂)-alkyl, CF₃, (C₃-C₇)-cycloalkyl, aryl, or heterocyclyl;

B is a 5-membered heteroaryl ring represented by any one of the general structures (i) to (x);

A is selected from (C Ci₂)-alkyl, (C₃-Ci₂)-cycloalkyl, aryl or heterocyclyl; wherein,

(C₃-Ci₂)-cycloalkyl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (Ci-Ci₂)-alkoxy; cyano, nitro, aryl, heterocyclyl, C(0)R_p, C(0)OR_p, NRpRq, C(0)NR_pR_q, SR_P, S(0)R_p or S0₂R_p;

aryl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (Ci-Ci₂)-alkoxy, cyano, nitro, (Ci-Ci₂)-alkyl, OCF₃, CF₃, (C₂-Ci₂)-alkenyl, (C₂- Ci₂)-alkynyl, (C₃-Ci₂)-cycloalkyl, aryl, aryloxy, heterocyclyl, O-heterocyclyl, C(0)R_p, C(0)OR_p, NRpR_q, C(0)NRpR_q, SR_P, S(0)R_p or S0₂R_p, or aryl may be fused with an unsubstituted or substituted 5 or 6-membered cycloalkyl ring optionally containing one or more heteroatoms selected from O, N or S;

with the proviso that A is not a methyl group.

8. The compound of formula 1 according to claim 7;

wherein,

B is

wherein 1 and 2 are the points of attachment of B to phenyl and to Z respectively;

Z is selected from:

indicates the point of attachment;

n is an integer selected from 1 -5;

m is 0 or 1 ;

Ri and R₂ are independently selected from hydrogen or (CrCi₂)-alkyl, or R! and R₂ can optionally form an unsubstituted or substituted (C₃-C₇) cycloalkyl ring;

R₃ is hydrogen or (CrCi₂)-alkyl;

R₅ is selected from hydrogen, (Ci-Ci₂)-alkyl, CF₃, (C₃-C₇)-cycloalkyl, aryl, or heterocyclyl; and

A is selected from (C Ci₂)-alkyl, (C₃-Ci₂)-cycloalkyl, aryl or heterocyclyl; wherein,

(Ci-Ci₂)-alkyl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (Ci-Ci₂)-alkoxy, cyano, (C₃-Ci₂)-cycloalkyl, aryl or heterocyclyl; (C₃-Ci₂)-cycloalkyl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (CrCi₂)-alkoxy, cyano, aryl or heterocyclyl;

aryl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (CrCi₂)-alkoxy, cyano, (CrCi₂)-alkyl, OCF₃, CF₃, (C₃-Ci₂)-cycloalkyl, aryl, aryloxy, heterocyclyl or O-heterocyclyl; or aryl may be fused with an unsubstituted or substituted 5 or 6-membered cycloalkyi ring optionally containing one or more heteroatoms selected from O, N or S;

with the proviso that A is not a methyl group.

9. The compound of formula 1 according to claim 7,

wherein,

B is

wherein 1 and 2 are the points of attachment of B to phenyl and to Z respectively;

Z is selected from:

indicates the point of attachment;

n is an integer selected from 1 -5;

m is 0 or 1 ;

Ri and R₂ are independently selected from hydrogen or (CrCi₂)-alkyl, or R! and R₂ can optionally form an unsubstituted or substituted (C₃-C₇) cycloalkyi ring;

R₃ is hydrogen or (CrCi₂)-alkyl;

R₅ is selected from hydrogen, (Ci-Ci₂)-alkyl, CF₃, (C₃-C₇)-cycloalkyl, aryl, or heterocyclyl; and

A is selected from (C Ci₂)-alkyl, (C₃-Ci₂)-cycloalkyl, aryl or heterocyclyl; wherein,

(Ci-Ci₂)-alkyl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (Ci-Ci₂)-alkoxy, cyano, (C₃-Ci₂)-cycloalkyl, aryl or heterocyclyl;

(C₃-Ci₂)-cycloalkyl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (C Ci₂)-alkoxy, cyano, aryl or heterocyclyl;

aryl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (Ci-Ci₂)-alkoxy, cyano, (Ci-Ci₂)-alkyl, OCF₃, CF₃, (C₃-Ci₂)-cycloalkyl, aryl, aryloxy, heterocyclyl or O-heterocyclyl; or aryl may be fused with an unsubstituted or substituted 5 or 6-membered cycloalkyi ring optionally containing one or more heteroatoms selected from O, N or S;

with the proviso that A is not a methyl group.

10. The compound of formula 1 according to claim 7,

wherein, B is

wherein 1 and 2 are the points of attachment of B to phenyl and to Z respectively; Z is selected from:

indicates the point of attachment;

n is an integer selected from 1 -5;

m is 0 or 1 ;

Ri and R₂ are independently selected from hydrogen or (CrCi₂)-alkyl, or R! and R₂ can optionally form an unsubstituted or substituted (C₃-C₇) cycloalkyl ring;

R₃ is hydrogen or (CrCi₂)-alkyl;

R₅ is selected from hydrogen, (Ci-Ci₂)-alkyl, CF₃, (C₃-C₇)-cycloalkyl, aryl, or heterocyclyl; and

A is selected from (C Ci₂)-alkyl, (C₃-Ci₂)-cycloalkyl, aryl or heterocyclyl; wherein,

with the proviso that A is not a methyl group.

1 1 . The compound of formula 1 according to claim 7,

wherein,

B is

wherein 1 and 2 are the points of attachment of B to phenyl and to Z respectively;

Z is selected from:

indicates the point of attachment;

n is an integer selected from 1 -5;

m is 0 or 1 ;

Ri and R₂ are independently selected from hydrogen or (CrCi₂)-alkyl, or R! and R₂ can optionally form an unsubstituted or substituted (C₃-C₇) cycloalkyi ring;

R₃ is hydrogen or (CrCi₂)-alkyl;

R₅ is selected from hydrogen, (Ci-Ci₂)-alkyl, CF₃, (C₃-C₇)-cycloalkyl, aryl, and heterocyclyl; and

A is selected from (C Ci₂)-alkyl, (C₃-Ci₂)-cycloalkyl, aryl or heterocyclyl; wherein,

(Ci-Ci₂)-alkyl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (Ci-Ci₂)-alkoxy, cyano, (C₃-Ci₂)-cycloalkyl, aryl or heterocyclyl;

(C₃-Ci₂)-cycloalkyl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (C Ci₂)-alkoxy, cyano, aryl or heterocyclyl;

aryl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (Ci-Ci₂)-alkoxy, cyano, (Ci-Ci₂)-alkyl, OCF₃, CF₃, (C₃-Ci₂)-cycloalkyl, aryl, aryloxy, heterocyclyl or O-heterocyclyl; or aryl may be fused with an unsubstituted or substituted 5 or 6-membered cycloalkyi ring optionally containing one or more heteroatoms selected from O, N or S;

with the proviso that A is not a methyl group.

12. The compound of formula 1 according to claim 1 represented by a compound of formula 1 c,

Formula 1 c

or a stereoisomer, tautomer, pharmaceutically acceptable salt, solvate or N-oxide thereof;

wherein,

Z is selected from:

indicates the point of attachment;

n is an integer selected from 1 -5;

m is 0 or 1 ;

Ri and R₂ are independently selected from hydrogen or (CrCi₂)-alkyl, or R! and R₂ can optionally form an unsubstituted or substituted (C₃-C₇) cycloalkyl ring;

R₃ is hydrogen or (CrCi₂)-alkyl;

R₅ is selected from hydrogen, (Ci-Ci₂)-alkyl, CF₃, (C₃-C₇)-cycloalkyl, aryl, or heterocyclyl;

B is a 5-membered heteroaryl ring represented by any one of the general structures (i) to (x);

A is selected from (C Ci₂)-alkyl, (C₃-Ci₂)-cycloalkyl, aryl or heterocyclyl; wherein,

aryl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (Ci-Ci₂)-alkoxy, cyano, nitro, (Ci-Ci₂)-alkyl, OCF₃, CF₃, (C₂-Ci₂)-alkenyl, (C₂- Ci₂)-alkynyl, (C₃-Ci₂)-cycloalkyl, aryl, aryloxy, heterocyclyl, O-heterocyclyl, C(0)R_p, C(0)OR_p, NR_pRq, C(0)NR_pR_q, SR_P, S(0)R_p or S0₂R_p or aryl may be fused with an unsubstituted or substituted 5 or 6-membered cycloalkyi ring optionally containing one or more heteroatoms selected from O, N or S;

heterocyclyl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (Ci-Ci₂)-alkoxy, cyano, nitro, (Ci-Ci₂)-alkyl, (C₂-Ci₂)-alkenyl, (C₂- Ci₂)-alkynyl, (C₃-Ci₂)-cycloalkyl, aryl, aryloxy, heterocyclyl, O-heterocyclyl, C(0)R_p, C(0)OR_p, NR_pRq, C(0)NRpR_q, SR_P, S(0)R_p or S0₂R_p; R_p and R_q are independently selected from hydrogen, (CrCi₂)-alkyl, aryl, aralkyi or heterocyclyl, or R_p and R_q together with the N to which they are attached optionally form a 3 to 7 membered ring;

with the proviso that A is not a methyl group.

13. The compound of formula 1 according to claim 12,

wherein,

B is

wherein 1 and 2 are the points of attachment of B to phenyl and to Z respectively;

Z is

indicates the point of attachment;

n is an integer selected from 1 -5;

m is 0 or 1 ;

Ri and R₂ are independently selected from hydrogen or (CrCi₂)-alkyl, or R! and R₂ can optionally form an unsubstituted or substituted (C₃-C₇) cycloalkyl ring; R₃ is hydrogen or (CrCi₂)-alkyl;

R₅ is selected from hydrogen, (CrCi₂)-alkyl, CF₃, (C₃-C₇)-cycloalkyl, aryl, or heterocyclyl; and

A is selected from (CrCi₂)-alkyl, (C₃-Ci₂)-cycloalkyl, aryl or heterocyclyl;

wherein,

(Ci-Ci₂)-alkyl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (Ci-Ci₂)-alkoxy, cyano, (C₃-Ci₂)-cycloalkyl, aryl or heterocyclyl;

(C₃-Ci₂)-cycloalkyl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (C Ci₂)-alkoxy, cyano, aryl or heterocyclyl;

aryl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (Ci-Ci₂)-alkoxy, cyano, (Ci-Ci₂)-alkyl, OCF₃, CF₃, (C₃-Ci₂)-cycloalkyl, aryl, aryloxy, heterocyclyl or O-heterocyclyl; or aryl may be fused with an unsubstituted or substituted 5 or 6-membered cycloalkyi ring optionally containing one or more heteroatoms selected from O, N or S;

with the proviso that A is not a methyl group. 14. The compound of formula 1 according to claim 12,

wherein,

B is

wherein 1 and 2 are the points of attachment of B to phenyl and to Z respectively;

Z is selected from:

indicates the point of attachment;

n is an integer selected from 1 -5;

m is 0 or 1 ;

Ri and R₂ are independently selected from hydrogen or (CrCi₂)-alkyl, or R! and R₂ can optionally form an unsubstituted or substituted (C₃-C₇) cycloalkyi ring;

R₃ is hydrogen or (CrCi₂)-alkyl;

R₅ is selected from hydrogen, (Ci-Ci₂)-alkyl, CF₃, (C₃-C₇)-cycloalkyl, aryl, or heterocyclyl; and

A is selected from (C Ci₂)-alkyl, (C₃-Ci₂)-cycloalkyl, aryl or heterocyclyl; wherein,

aryl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (Ci-Ci₂)-alkoxy, cyano, (Ci-Ci₂)-alkyl, OCF₃, CF₃, (C₃-Ci₂)-cycloalkyl, aryl, aryloxy, heterocyclyl or O-heterocyclyl; or aryl may be fused with an unsubstituted or substituted 5 or 6-membered cycloalkyi ring optionally containing one or more heteroatoms selected from O, N or S;

with the proviso that A is not a methyl group.

15. The compound of formula 1 according to claim 12,

wherein,

B is

wherein 1 and 2 are the points of attachment of B to phenyl and to Z respectively;

Z is selected from:

indicates the point of attachment;

n is an integer selected from 1 -5;

m is 0 or 1 ;

Ri and R₂ are independently selected from hydrogen or (CrCi₂)-alkyl, or R! and R₂ can optionally form an unsubstituted or substituted (C₃-C₇) cycloalkyl ring;

R₃ is hydrogen or (CrCi₂)-alkyl;

R₅ is selected from hydrogen, (Ci-Ci₂)-alkyl, CF₃, (C₃-C₇)-cycloalkyl, aryl, or heterocyclyl; and

A is selected from (C Ci₂)-alkyl, (C₃-Ci₂)-cycloalkyl, aryl or heterocyclyl; wherein, (CrCi₂)-alkyl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (CrCi₂)-alkoxy, cyano, (C₃-Ci₂)-cycloalkyl, aryl or heterocyclyl;

(C₃-Ci₂)-cycloalkyl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (C Ci₂)-alkoxy, cyano, aryl or heterocyclyl;

aryl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (Ci-Ci₂)-alkoxy, cyano, (Ci-Ci₂)-alkyl, OCF₃, CF₃, (C₃-Ci₂)-cycloalkyl, aryl, aryloxy, heterocyclyl or O-heterocyclyl; or aryl may be fused with an unsubstituted or substituted 5 or 6-membered cycloalkyi ring optionally containing one or more heteroatoms selected from O, N or S;

with the proviso that A is not a methyl group. 16. The compound of formula 1 according to claim 12,

wherein,

B is

wherein 1 and 2 are the points of attachment of B to phenyl and to Z respectively;

Z is selected from:

indicates the point of attachment;

n is an integer selected from 1 -5;

m is 0 or 1 ;

Ri and R₂ are independently selected from hydrogen or (CrCi₂)-alkyl, or R! and R₂ can optionally form an unsubstituted or substituted (C₃-C₇) cycloalkyi ring;

R₃ is hydrogen or (CrCi₂)-alkyl;

R₅ is selected from hydrogen, (Ci-Ci₂)-alkyl, CF₃, (C₃-C₇)-cycloalkyl, aryl, or heterocyclyl; and

A is selected from (C Ci₂)-alkyl, (C₃-Ci₂)-cycloalkyl, aryl or heterocyclyl; wherein,

(Ci-Ci₂)-alkyl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (Ci-Ci₂)-alkoxy, cyano, (C₃-Ci₂)-cycloalkyl, aryl or heterocyclyl;

(C₃-Ci₂)-cycloalkyl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (C Ci₂)-alkoxy, cyano, aryl or heterocyclyl;

aryl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (Ci-Ci₂)-alkoxy, cyano, (Ci-Ci₂)-alkyl, OCF₃, CF₃, (C₃-Ci₂)-cycloalkyl, aryl, aryloxy, heterocyclyl or O-heterocyclyl; or aryl may be fused with an unsubstituted or substituted 5 or 6-membered cycloalkyi ring optionally containing one or more heteroatoms selected from O, N or S;

with the proviso that A is not a methyl group.

17. The compound of formula 1 according to claim 1 represented by a compound of formula 1 d,

Formula 1 d

or a stereoisomer, tautomer, pharmaceutically acceptable salt, solvate or N-oxide thereof;

wherein,

Z is selected from:

indicates the point of attachment;

n is an integer selected from 1 -5;

m is 0 or 1 ;

Ri and R₂ are independently selected from hydrogen or (CrCi₂)-alkyl, or Ri and R₂ can optionally form an unsubstituted or substituted (C₃-C₇) cycloalkyl ring;

R₃ is hydrogen or (CrCi₂)-alkyl;

R₅ is selected from hydrogen, (Ci-Ci₂)-alkyl, CF₃, (C₃-C₇)-cycloalkyl, aryl, or heterocyclyl;

B is a 5-membered heteroaryl ring represented by any one of the general structures (i) to (x);

A is selected from (C Ci₂)-alkyl, (C₃-Ci₂)-cycloalkyl, aryl or heterocyclyl; wherein,

(Ci-Ci₂)-alkyl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (Ci-Ci₂)-alkoxy, cyano, (C₃-Ci₂)-cycloalkyl, aryl or heterocyclyl;

(C₃-Ci₂)-cycloalkyl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (C Ci₂)-alkoxy, cyano, aryl or heterocyclyl;

aryl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (Ci-Ci₂)-alkoxy, cyano, (Ci-Ci₂)-alkyl, OCF₃, CF₃, (C₃-Ci₂)-cycloalkyl, aryl, aryloxy, heterocyclyl or O-heterocyclyl; or aryl may be fused with an unsubstituted or substituted 5 or 6-membered cycloalkyi ring optionally containing one or more heteroatoms selected from O, N or S;

with the proviso that A is not a methyl group. 18. The compound of formula 1 according to claim 1 , represented by a compound of formula 1 e,

Formula 1 e

or a stereoisomer, tautomer, pharmaceutically acceptable salt, solvate or N-oxide thereof;

wherein,

Z is selected from:

indicates the point of attachment;

n is an integer selected from 1 -5;

m is 0 or 1 ;

Ri and R₂ are independently selected from hydrogen or (CrCi₂)-alkyl, or R! and R₂ can optionally form an unsubstituted or substituted (C₃-C₇) cycloalkyl ring;

R₃ is hydrogen or (CrCi₂)-alkyl;

R₅ is selected from hydrogen, (Ci-Ci₂)-alkyl, CF₃, (C₃-C₇)-cycloalkyl, aryl, or heterocyclyl;

B is a 5-membered heteroaryl ring represented by any one of the general structures (i) to (x);

R₆ is selected from hydrogen, methyl, cyano or nitro; and

A is selected from (C Ci₂)-alkyl, (C₃-Ci₂)-cycloalkyl, aryl or heterocyclyl; wherein,

(Ci-Ci₂)-alkyl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (Ci-Ci₂)-alkoxy, cyano, (C₃-Ci₂)-cycloalkyl, aryl or heterocyclyl;

(C₃-Ci₂)-cycloalkyl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (C Ci₂)-alkoxy, cyano, aryl or heterocyclyl;

aryl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (Ci-Ci₂)-alkoxy, cyano, (Ci-Ci₂)-alkyl, OCF₃, CF₃, (C₃-Ci₂)-cycloalkyl, aryl, aryloxy, heterocyclyl or O-heterocyclyl; or aryl may be fused with an unsubstituted or substituted 5 or 6-membered cycloalkyi ring optionally containing one or more heteroatoms selected from O, N or S;

with the proviso that A is not a methyl group.

19. A compound of formula 1 according to any of the claims 1 -18, wherein A is an unsubstituted aryl or an aryl substituted with one or more groups selected from halogen, hydroxy, (CrCi₂)-alkoxy, cyano, unsubstituted or substituted (CrCi₂)-alkyl, OCF₃, CF₃, unsubstituted or substituted (C₃-Ci₂)-cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted aryloxy, unsubstituted or substituted heterocyclyl, or O-heterocyclyl.

20. A compound of formula 1 according to claim 19, wherein A is an aryl group and said aryl group may be fused with an unsubstituted or substituted 5 or 6-membered cycloalkyl ring optionally containing one or more heteroatoms selected from O, N or S.

21 . A compound of formula 1 according to any of the claims 1 -18, wherein A is an unsubstituted heterocyclyl or a heterocyclyl substituted with one or more groups selected from halogen, hydroxy, (CrCi₂)-alkoxy, cyano, unsubstituted or substituted (Ci-Ci₂)-alkyl, unsubstituted or substituted (C₃-Ci₂)-cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted aryloxy, heterocyclyl or O-heterocyclyl.

22. A compound of formula 1 according to any of the claims 1 -18, wherein A is an unsubstituted (C₃-Ci₂)-cycloalkyl or (C₃-Ci₂)-cycloalkyl substituted with one or more groups selected from halogen, hydroxy, unsubstituted or substituted (Ci-Ci₂)-alkyl, (d- Ci₂)-alkoxy, cyano, nitro, unsubstituted or substituted aryl, or unsubstituted or substituted heterocyclyl.

23. A compound of formula 1 according to any of the claims 1 -18, wherein A is an unsubstituted (Ci-Ci₂)-alkyl or (Ci-Ci₂)-alkyl substituted with one or more groups selected from halogen, hydroxy, (Ci-Ci₂)-alkoxy, cyano, unsubstituted or substituted (C₃-Ci₂)-cycloalkyl, unsubstituted or substituted aryl, or unsubstituted or substituted heterocyclyl; with the proviso that A is not a methyl group. 24. The compound of formula 1 according to any one of the preceding claims 1 - 23 selected from:

Methyl 3-(5-(4-(3-(3-(trifluoromethyl)phenyl)ureido)phenyl)thiazol-2-yl) propanoate; 3-(5-(4-(3-(3-(Trifluoromethyl)phenyl)ureido)phenyl)thiazol-2-yl)propanoic acid;

Methyl 3-(5-(4-(3-(2-chlorophenyl)ureido)phenyl)thiazol-2-yl)propanoate; 3-(5-(4-(3-(2-Chlorophenyl)ureido)phenyl)thiazol-2-yl)propanoic acid;

Methyl 3-(5-(4-(3-cyclohexylureido)phenyl)thiazol-2-yl)propanoate;

3-(5-(4-(3-Cyclohexylureido)phenyl)thiazol-2-yl)propanoic acid;

Methyl 3-(5-(4-(3-(4-chloro-2-phenoxyphenyl)ureido)phenyl)thiazol-2-yl) propanoate;

3-(5-(4-(3-(4-Chloro-2-phenoxyphenyl)ureido)phenyl)thiazol-2-yl)propanoic acid;

Methyl 3-(5-(4-(4-t-butylbenzamido)phenyl)thiazol-2-yl)propanoate;

3-(5-(4-(4-t-Butylbenzamido)phenyl)thiazol-2-yl)propanoic acid;

Methyl 3-(5-(4-(4-pentylbenzamido)phenyl)thiazol-2-yl)propanoate;

3-(5-(4-(4-Pentylbenzamido)phenyl)thiazol-2-yl)propanoic acid;

Methyl 3-(5-(4-(3-ethoxy-5-(methoxymethyl)benzamido)phenyl)thiazol-2-yl) propanoate;

3-(5-(4-(3-Ethoxy-5-(methoxymethyl)benzamido)phenyl)thiazol-2-yl)propanoic acid;

Methyl 3-(5-(4-(4-pentylbenzamido)phenyl)thiazol-2-yl)propanoate;

3-(5-(4-(2-Naphthamido)phenyl)thiazol-2-yl)propanoic acid;

Methyl 3-(5-(4-(4-butoxybenzamido)phenyl)thiazol-2-yl)propanoate;

3-(5-(4-(4-Butoxybenzamido)phenyl)thiazol-2-yl)propanoic acid;

Methyl 3-(5-(4-(2,4-dimethoxyphenylsulfonamido)phenyl)thiazol-2-yl) propanoate;

3-(5-(4-(2,4-Dimethoxyphenylsulfonamido)phenyl)thiazol-2-yl)propanoic acid;

Methyl 3-(5-(4-(3-(2-chlorophenyl)ureido)phenyl)thiazol-2-yl)-2,2-dimethyl propanoate;

3-(5-(4-(3-(2-Chlorophenyl)ureido)phenyl)thiazol-2-yl)-2,2-dimethylpropanoic acid;

Methyl 2,2-dimethyl-3-(5-(4-(3-(4-(trifluoromethyl)phenyl)ureido)phenyl) thiazol -2- yl)propanoate;

2,2-Dimethyl-3-(5-(4-(3-(4-(trifluoromethyl)phenyl)ureido)phenyl)thiazol-2-yl) propanoic acid;

Methyl 2,2-dimethyl-3-(5-(4-(3-(4-(trifluoromethyl)phenyl)ureido)phenyl) thiazol-2- yl)propanoate;

3-(5-(4-(3-(4-Fluorophenyl)ureido)phenyl)thiazol-2-yl)-2,2-dimethylpropanoic acid; Methyl 3-(5-(4-(3-(4-methoxyphenyl)ureido)phenyl)thiazol-2-yl)-2,2-dimethyl propanoate;

3-(5-(4-(3-(4-Methoxyphenyl)ureido)phenyl)thiazol-2-yl)-2,2-dimethyl propanoic acid; Methyl 3-(5-(4-(3-cyclohexylureido)phenyl)thiazol-2-yl)-2,2-dimethyl propanoate;

3-(5-(4-(3-Cyclohexylureido)phenyl)thiazol-2-yl)-2,2-dimethylpropanoic acid;

Methyl 3-(5-(4-(3-(4-chloro-2-phenoxyphenyl)ureido)phenyl)thiazol-2-yl)-2,2- dimethylpropanoate; 3-(5-(4-(3-(4-Chloro-2-phenoxyphenyl)ureido)phenyl)thiazol-2-yl)-2,2-dimethylpropanoic acid;

Methyl 3-(5-(4-(4-tert-butylbenzamido)phenyl)thiazol-2-yl)-2,2-dimethyl propanoate;

3-(5-(4-(4-t-Butylbenzamido)phenyl)thiazol-2-yl)-2,2-dimethylpropanoic acid;

Methyl 3-(5-(4-biphenyl-4-ylcarboxamidophenyl)thiazol-2-yl)-2,2-dimethyl propanoate;

3- (5-(4-Biphenyl-4-ylcarboxamidophenyl)thiazol-2-yl)-2,2-dimethylpropanoic acid; Methyl 4-(5-(4-(3-(3-(trifluoromethyl)phenyl)ureido)phenyl)thiazol-2-yl) butanoate;

4- (5-(4-(3-(3-(Trifluoromethyl)phenyl)ureido)phenyl)thiazol-2-yl)butanoic acid;

Methyl 4-(5-(4-(3-(2-chlorophenyl)ureido)phenyl)thiazol-2-yl)butanoate;

4-(5-(4-(3-(2-Chlorophenyl)ureido)phenyl)thiazol-2-yl)butanoic acid;

Methyl 4-(5-(4-(3-(3,4-dimethylphenyl)ureido)phenyl)thiazol-2-yl)butanoate;

4-(5-(4-(3-(3,4-Dimethylphenyl)ureido)phenyl)thiazol-2-yl)butanoic acid;

Methyl 4-(5-(4-(3-(4-chloro-2-phenoxyphenyl)ureido)phenyl)thiazol-2-yl) butanoate;

4-(5-(4-(3-(4-Chloro-2-phenoxyphenyl)ureido)phenyl)thiazol-2-yl)butanoic acid;

Methyl 4-(5-(4-(4-t-butylbenzamido)phenyl)thiazol-2-yl)butanoate;

4-(5-(4-(4-t-Butylbenzamido)phenyl)thiazol-2-yl)butanoic acid;

Methyl 4-(5-(4-(4-pentylbenzamido)phenyl)thiazol-2-yl)butanoate;

4-(5-(4-(4-Pentylbenzamido)phenyl)thiazol-2-yl)butanoic acid;

Methyl 4-(5-(4-biphenyl-4-ylcarboxamidophenyl)thiazol-2-yl)butanoate;

4-(5-(4-Biphenyl-4-ylcarboxamidophenyl)thiazol-2-yl)butanoic acid;

Methyl 4-(5-(4-(2,4-dimethoxyphenylsulfonamido)phenyl)thiazol-2-yl)butanoate;

4-(5-(4-(2,4-Dimethoxyphenylsulfonamido)phenyl)thiazol-2-yl)butanoic acid;

Methyl 3,3-dimethyl-4-(5-(4-(3-(3-(trifluoromethyl)phenyl)ureido)phenyl) thiazol-2- yl)butanoate;

3,3-Dimethyl-4-(5-(4-(3-(3-(trifluoromethyl)phenyl)ureido)phenyl)thiazol-2-yl) butanoic acid;

Methyl 4-(5-(4-(3-(2-chlorophenyl)ureido)phenyl)thiazol-2-yl)-3,3-dimethyl butanoate; 4-(5-(4-(3-(2-Chlorophenyl)ureido)phenyl)thiazol-2-yl)-3,3-dimethylbutanoic acid;

Methyl 4-(5-(4-(3-(4-chloro-2-phenoxyphenyl)ureido)phenyl)thiazol-2-yl)-3,3- dimethylbutanoate;

4-(5-(4-(3-(4-Chloro-2-phenoxyphenyl)ureido)phenyl)thiazol-2-yl)-3,3-dimethyl butanoic acid;

Methyl 4-(5-(4-(4-tert-butylbenzamido)phenyl)thiazol-2-yl)-3,3-dimethyl butanoate; 4-(5-(4-(4-t-Butylbenzamido)phenyl)thiazol-2-yl)-3,3-dimethylbutanoic acid; Methyl 4-(5-(4-biphenyl-4-ylcarboxamidophenyl)thiazol-2-yl)-3,3-dimethyl butanoate; 4-(5-(4-Biphenyl-4-ylcarboxamidophenyl)thiazol-2-yl)-3,3-dimethylbutanoic acid;

Methyl 3,3-dimethyl-4-(5-(4-(4-pentylbenzamido)phenyl)thiazol-2-yl) butanoate;

3,3-Dimethyl-4-(5-(4-(4-pentylbenzamido)phenyl)thiazol-2-yl)butanoic acid;

Methyl 4-(5-(4-(2,4-dimethoxyphenylsulfonamido)phenyl)thiazol-2-yl)-3,3- dimethylbutanoate;

4-(5-(4-(2,4-Dimethoxyphenylsulfonamido)phenyl)thiazol-2-yl)-3,3-dimethylbutanoic acid;

Methyl 2,2-dimethyl-4-(5-(4-(3-(3-(trifluoromethyl)phenyl)ureido)phenyl) thiazol-2- yl)butanoate;

2,2-Dimethyl-4-(5-(4-(3-(3-(trifluoromethyl)phenyl)ureido)phenyl)thiazol-2-yl) butanoic acid;

Methyl 4-(5-(4-(3-(2-chlorophenyl)ureido)phenyl)thiazol-2-yl)-2,2-dimethyl butanoate; 4-(5-(4-(3-(2-Chlorophenyl)ureido)phenyl)thiazol-2-yl)-2,2-dimethylbutanoic acid;

Methyl 4-(5-(4-(3-(4-chloro-2-phenoxyphenyl)ureido)phenyl)thiazol-2-yl)-2,2- dimethylbutanoate;

4-(5-(4-(3-(4-Chloro-2-phenoxyphenyl)ureido)phenyl)thiazol-2-yl)-2,2-dimethylbutanoic acid;

Methyl 4-(5-(4-(3-cyclohexylureido)phenyl)thiazol-2-yl)-2,2-dimethyl butanoate;

4-(5-(4-(3-Cyclohexylureido)phenyl)thiazol-2-yl)-2,2-dimethylbutanoic acid;

Methyl 4-(5-(4-(3-(4-fluorophenyl)ureido)phenyl)thiazol-2-yl) y-2,2-dimethyl butanoate; 4-(5-(4-(3-(2-Chlorophenyl)ureido)phenyl)thiazol-2-yl)-2,2-dimethylbutanoic acid;

Methyl 4-(5-(4-(3-(4-methoxyphenyl)ureido)phenyl)thiazol-2-yl)-2,2-dimethyl butanoate; 4-(5-(4-(3-(4-Methoxyphenyl)ureido)phenyl)thiazol-2-yl)-2,2-dimethyl butanoic acid; Methyl 4-(5-(4-(3-(4-isopropylphenyl)ureido)phenyl)thiazol-2-yl)-2,2-dimethyl butanoate; 4-(5-(4-(3-(4-lsopropylphenyl)ureido)phenyl)thiazol-2-yl)-2,2-dimethyl butanoic acid; Methyl 4-(5-(4-(3-(2,4-difluorophenyl)ureido)phenyl)thiazol-2-yl)-2,2-dimethylbutanoate; 4-(5-(4-(3-(2,4-Difluorophenyl)ureido)phenyl)thiazol-2-yl)-2,2-dimethyl butanoic acid; Methyl 4-(5-(4-(3-(2-fluorophenyl)ureido)phenyl)thiazol-2-yl)-2,2-dimethyl butanoate; 4-(4-(4-(3-(2-Fluorophenyl)ureido)phenyl)-3H-pyrrol-2-yl)-2,2-dimethyl butanoic acid; Methyl 4-(5-(4-(4-t-butylbenzamido)phenyl)thiazol-2-yl)-2,2-dimethyl butanoate;

4-(5-(4-(4-t-Butylbenzamido)phenyl)thiazol-2-yl)-2,2-dimethylbutanoic acid;

Methyl 4-(5-(4-biphenyl-4-ylcarboxamidophenyl)thiazol-2-yl)-2,2-dimethyl butanoate; 4-(5-(4-Biphenyl-4-ylcarboxamidophenyl)thiazol-2-yl)-2,2-dimethylbutanoic acid; Methyl 2,2-dimethyl-4-(5-(4-(4-(oxazol-5-yl)benzamido)phenyl)thiazol-2-yl) butanoate; 2,2-Dimethyl-4-(5-(4-(4-(oxazol-5-yl)benzamido)phenyl)thiazol-2-yl)butanoic acid; Methyl 2,2-dimethyl-4-(5-(4-(4-phenylthiazole-2-carboxamido)phenyl)thiazol-2-yl) butanoate;

2,2-Dimethyl-4-(5-(4-(4-phenylthiazole-2-carboxamido)phenyl)thiazol-2-yl) butanoic acid;

Methyl 3-(5-(4-(3-(2-chlorophenyl)ureido)phenyl)oxazol-2-yl)-2,2-dimethyl propanoate; 3-(5-(4-(3-(2-Chlorophenyl)ureido)phenyl)oxazol-2-yl)-2,2-dimethylpropanoic acid; Methyl 2,2-dimethyl-3-(5-(4-(3-(4-(trifluoromethyl)phenyl)ureido)phenyl) oxazol-2- yl)propanoate;

2,2-Dimethyl-3-(5-(4-(3-(4-(trifluoromethyl)phenyl)ureido)phenyl)oxazol-2-yl) propanoic acid;

Methyl 3-(5-(4-(3-(4-fluorophenyl)ureido)phenyl)oxazol-2-yl)-2,2-dimethyl propanoate; 3-(5-(4-(3-(4-Fluorophenyl)ureido)phenyl)oxazol-2-yl)-2,2-dimethylpropanoic acid; Methyl 3-(5-(4-(3-(4-methoxyphenyl)ureido)phenyl)oxazol-2-yl)-2,2-dimethyl propanoate;

3-(5-(4-(3-(4-Methoxyphenyl)ureido)phenyl)oxazol-2-yl)-2,2-dimethyl propanoic acid; Methyl 3-(5-(4-(3-(4-chloro-2-phenoxyphenyl)ureido)phenyl)oxazol-2-yl)-2,2- dimethylpropanoate;

3-(5-(4-(3-(4-Chloro-2-phenoxyphenyl)ureido)phenyl)oxazol-2-yl)-2,2-dimethyl propanoic acid;

Methyl 3-(5-(4-(4-t-butylbenzamido)phenyl)oxazol-2-yl)-2,2-dimethyl propanoate;

3-(5-(4-(4-t-Butylbenzamido)phenyl)oxazol-2-yl)-2,2-dimethylpropanoic acid;

Methyl 3-(5-(4-biphenyl-4-ylcarboxamidophenyl)oxazol-2-yl)-2,2-dimethyl propanoate;

3- (5-(4-Biphenyl-4-ylcarboxamidophenyl)oxazol-2-yl)-2,2-dimethylpropanoic acid; Methyl 4-(5-(4-(3-(3-(trifluoromethyl)phenyl)ureido)phenyl)thiazol-2-yl)

cyclohexanecarboxylate;

4- (5-(4-(3-(3-(Trifluoromethyl)phenyl)ureido)phenyl)thiazol-2-yl)cyclohexane carboxylic acid;

Methyl 4-(5-(4-(3-p-tolylureido)phenyl)thiazol-2-yl)cyclohexanecarboxylate;

4-(5-(4-(3-p-Tolylureido)phenyl)thiazol-2-yl)cyclohexanecarboxylic acid;

Methyl 4-(5-(4-(3-(2,4-difluorophenyl)ureido)phenyl)thiazol-2yl)cyclohexane carboxylate;

4-(5-(4-(3-(2,4-Difluorophenyl)ureido)phenyl)thiazol-2-yl)cyclohexane carboxylic acid; Methyl 4-(5-(4-(3-(2-fluorophenyl)ureido)phenyl)thiazol-2-yl)cyclohexane carboxylate; 4-(5-(4-(3-(2-Fluorophenyl)ureido)phenyl)thiazol-2-yl)cyclohexanecarboxylic acid; Methyl 4-(5-(4-(3-cyclohexylureido)phenyl)thiazol-2-yl)cyclohexane carboxylate; 4-(5-(4-(3-Cyclohexylureido)phenyl)thiazol-2-yl)cyclohexanecarboxylic acid;

Methyl 4-(5-(4-(3-(3-chlorophenyl)ureido)phenyl)thiazol-2-yl)cyclohexane carboxylate; 4-(5-(4-(3-(3-Chlorophenyl)ureido)phenyl)thiazol-2-yl)cyclohexanecarboxylic acid; Methyl 4-(5-(4-(3-(4-chlorophenyl)ureido)phenyl)thiazol-2-yl)cyclohexane carboxylate; 4-(5-(4-(3-(4-Chlorophenyl)ureido)phenyl)thiazol-2-yl)cyclohexanecarboxylic acid; Methyl 4-(5-(4-(3-(2-chloro-4-(trifluoromethyl)phenyl)ureido)phenyl)thiazol-2-yl) cyclohexanecarboxylate;

4-(5-(4-(3-(2-Chloro-4-(trifluoromethyl)phenyl)ureido)phenyl)thiazol-2-yl)

cyclohexanecarboxylic acid;

Methyl 4-(5-(4-(3-(2-chloro-5-methylphenyl)ureido)phenyl)thiazol-2-yl) cyclo hexanecarboxylate;

4-(5-(4-(3-(2-Chloro-5-methylphenyl)ureido)phenyl)thiazol-2-yl)cyclohexane carboxylic acid;

Methyl 4-(5-(4-(3-(3-chloro-2-fluorophenyl)ureido)phenyl)thiazol-2-yl)cyclo

hexanecarboxylate;

4-(5-(4-(3-(3-Chloro-2-fluorophenyl)ureido)phenyl)thiazol-2-yl)cyclohexane carboxylic acid;

Methyl 4-(5-(4-(3-(4-methoxy-2-methylphenyl)ureido)phenyl)thiazol-2-yl)

cyclohexanecarboxylate;

4-(5-(4-(3-(4-Methoxy-2-methylphenyl)ureido)phenyl)thiazol-2-yl)cyclo

hexanecarboxylic acid;

Methyl 4-(5-(4-(3-benzo[d][1 ,3]dioxol-5-ylureido)phenyl)thiazol-2-yl)cyclo

hexanecarboxylate;

4-(5-(4-(3-Benzo[d][1 ,3]dioxol-5-ylureido)phenyl)thiazol-2-yl)cyclohexane carboxylic acid;

Methyl 4-(5-(4-(3-(2-chloro-6-(trifluoromethyl)phenyl)ureido)phenyl)thiazol-2- yl)cyclohexanecarboxylate;

4-(5-(4-(3-(2-Chloro-6-(trifluoromethyl)phenyl)ureido)phenyl)thiazol-2-yl)

cyclohexanecarboxylic acid;

Methyl 4-(5-(4-(3-(4-chloro-2-(trifluoromethyl)phenyl)ureido)phenyl)thiazol-2- yl)cyclohexanecarboxylate; 4-(5-(4-(3-(4-Chloro-2-(trifluoromethyl)phenyl)ureido)phenyl)thiazol-2-yl)

cyclohexanecarboxylic acid;

Methyl 4-(5-(4-(3-(2-chloro-6-methylphenyl)ureido)phenyl)thiazol-2-yl) cyclo hexanecarboxylate;

4-(5-(4-(3-(2-Chloro-6-methylphenyl)ureido)phenyl)thiazol-2-yl)cyclohexane carboxylic acid;

Methyl 4-(5-(4-(3-(5-chloro-2-methylphenyl)ureido)phenyl)thiazol-2-yl) cyclo hexanecarboxylate;

4-(5-(4-(3-(5-Chloro-2-methylphenyl)ureido)phenyl)thiazol-2-yl)cyclohexane carboxylic acid;

Methyl 4-(5-(4-(3-(2-(trifluoromethyl)phenyl)ureido)phenyl)thiazol-2-yl)cyclo hexanecarboxylate;

4-(5-(4-(3-(2-(Trifluoromethyl)phenyl)ureido)phenyl)thiazol-2-yl)cyclohexane carboxylic acid;

Methyl 4-(5-(4-(3-(2-(trifluoromethoxy)phenyl)ureido)phenyl)thiazol-2-yl)

cyclohexanecarboxylate;

4-(5-(4-(3-(2-(Trifluoromethoxy)phenyl)ureido)phenyl)thiazol-2-yl)cyclohexane carboxylic acid;

Methyl 4-(5-(4-(3-(4-phenoxyphenyl)ureido)phenyl)thiazol-2-yl)cyclohexane carboxylate;

4-(5-(4-(3-(4-Phenoxyphenyl)ureido)phenyl)thiazol-2-yl)cyclohexane carboxylic acid; Methyl 4-(5-(4-(3-(4-chloro-2-fluorophenyl)ureido)phenyl)thiazol-2-yl)cyclo

hexanecarboxylate;

4-(5-(4-(3-(4-Chloro-2-fluorophenyl)ureido)phenyl)thiazol-2-yl)cyclohexane carboxylic acid;

Methyl 4-(5-(4-(3-(2-fluoro-5-methylphenyl)ureido)phenyl)thiazol-2-yl)cyclo

hexanecarboxylate;

4-(5-(4-(3-(2-Fluoro-5-methylphenyl)ureido)phenyl)thiazol-2-yl)cyclohexane carboxylic acid;

Methyl 4-(5-(4-(3-(2-fluoro-6-(trifluoromethyl)phenyl)ureido)phenyl)thiazol-2- yl)cyclohexanecarboxylate;

4-(5-(4-(3-(2-Fluoro-6-(trifluoromethyl)phenyl)ureido)phenyl)thiazol-2-yl)

cyclohexanecarboxylic acid;

Methyl 4-(5-(4-(3-(3-fluorophenyl)ureido)phenyl)thiazol-2-yl)cyclohexane carboxylate; 4-(5-(4-(3-(3-Fluorophenyl)ureido)phenyl)thiazol-2-yl)cyclohexanecarboxylic acid;

Methyl 4-(5-(4-(3-(3,4-difluorophenyl)ureido)phenyl)thiazol-2-yl)cyclohexane

carboxylate;

4-(5-(4-(3-(3,4-Difluorophenyl)ureido)phenyl)thiazol-2-yl)cyclohexane carboxylic acid; Methyl 4-(5-(4-(3-(3,5-difluorophenyl)ureido)phenyl)thiazol-2-yl)cyclohexane

carboxylate;

4-(5-(4-(3-(3,5-Difluorophenyl)ureido)phenyl)thiazol-2-yl)cyclohexane carboxylic acid; Methyl 4-(5-(4-(3-(2,6-difluorophenyl)ureido)phenyl)thiazol-2-yl)cyclohexane

carboxylate;

4-(5-(4-(3-(2,6-Difluorophenyl)ureido)phenyl)thiazol-2-yl)cyclohexane carboxylic acid; Methyl 4-(5-(4-(3-(2,3,4-trifluorophenyl)ureido)phenyl)thiazol-2-yl)cyclo

hexanecarboxylate;

4-(5-(4-(3-(2,3,4-Trifluorophenyl)ureido)phenyl)thiazol-2-yl)cyclohexane carboxylic acid; Methyl 4-(5-(4-(3-(2-chlorophenyl)ureido)phenyl)thiazol-2-yl)cyclohexane carboxylate; 4-(5-(4-(3-(2-Chlorophenyl)ureido)phenyl)thiazol-2-yl)cyclohexanecarboxylic

acid;

Methyl 4-(5-(4-(3-(4-chloro-2-phenoxyphenyl)ureido)phenyl)thiazol-2-yl)

cyclohexanecarboxylate;

4-(5-(4-(3-(4-Chloro-2-phenoxyphenyl)ureido)phenyl)thiazol-2-yl)cyclohexane carboxylic acid;

Methyl 4-(5-(4-(3-phenylureido)phenyl)thiazol-2-yl)cyclohexanecarboxylate;

4-(5-(4-(3-Phenylureido)phenyl)thiazol-2-yl)cyclohexanecarboxylic acid;

Methyl 4-(5-(4-(4-t-butylbenzamido)phenyl)thiazol-2-yl)cyclohexane carboxylate;

4-(5-(4-(4-t-Butylbenzamido)phenyl)thiazol-2-yl)cyclohexanecarboxylic acid;

Methyl 4-(5-(4-(2-chlorobenzamido)phenyl)thiazol-2-yl) cyclohexane carboxylate;

4-(5-(4-(2-Chlorobenzamido)phenyl)thiazol-2-yl)cyclohexanecarboxylic acid;

Methyl 4-(5-(4-(5-phenyloxazole-2-carboxamido)phenyl)thiazol-2-yl) cyclohexane carboxylate;

4-(5-(4-(5-Phenyloxazole-2-carboxamido)phenyl)thiazol-2-yl)cyclohexane carboxylic acid;

Methyl 4-(5-(4-(3-(4-methoxyphenyl)thioureido)phenyl)thiazol-2-yl) cyclo

hexanecarboxylate;

Methyl 4-(5-(4-(3-(4-chlorophenyl)thioureido)phenyl)thiazol-2-yl)cyclo

hexanecarboxylate; Methyl 4-(5-(4-(3-(2-chlorophenyl)ureido)phenyl)oxazol-2-yl)cyclohexane carboxylate;

4-(5-(4-(3-(2-Chlorophenyl)ureido)phenyl)oxazol-2-yl)cyclohexanecarboxylic acid;

Methyl 4-(5-(4-(3-phenylureido)phenyl)oxazol-2-yl)cyclohexanecarboxylate;

4-(5-(4-(3-Phenylureido)phenyl)oxazol-2-yl)cyclohexanecarboxylic acid;

Methyl 4-(5-(4-(3-(3-chlorophenyl)ureido)phenyl)oxazol-2-yl)cyclohexane carboxylate;

4-(5-(4-(3-(3-Chlorophenyl)ureido)phenyl)oxazol-2-yl)cyclohexanecarboxylic acid;

Methyl 4-(5-(4-(3-(2-methoxyphenyl)ureido)phenyl)oxazol-2-yl) cyclohexane carboxylate;

4-(5-(4-(3-(2-Methoxyphenyl)ureido)phenyl)oxazol-2-yl)cyclohexane carboxylic acid; Methyl 4-(5-(4-(2-chlorobenzamido)phenyl)oxazol-2-yl)cyclohexane carboxylate; 4-(5-(4-(2-Chlorobenzamido)phenyl)oxazol-2-yl)cyclohexanecarboxylic acid;

Methyl 4-(5-(4-(4-t-butylbenzamido)phenyl)oxazol-2-yl)cyclohexane carboxylate; 4-(5-(4-(4-t-Butylbenzamido)phenyl)oxazol-2-yl)cyclohexanecarboxylic acid;

(1 r,4r)-Methyl 4-(3-(4-(3-(2-chlorophenyl)ureido)phenyl)-1 ,2,4-oxadiazol-5-yl) cyclohexanecarboxylate;

(1 r,4r)-4-(3-(4-(3-(2-Chlorophenyl)ureido)phenyl)-1 ,2,4-oxadiazol-5-yl)cyclo hexanecarboxylic acid;

(1 r,4r)-Methyl 4-(3-(4-(3-(2,4-difluorophenyl)ureido)phenyl)-1 ,2,4-oxadiazol-5-yl) cyclohexanecarboxylate;

(1 r,4r)-4-(3-(4-(3-(2,4-Difluorophenyl)ureido)phenyl)-1 ,2,4-oxadiazol-5-yl)

cyclohexanecarboxylic acid;

(1 r,4r)-Methyl 4-(3-(4-(3-p-tolylureido)phenyl)-1 ,2,4-oxadiazol-5-yl)cyclo hexane carboxylate;

(1 r,4r)-4-(3-(4-(3-p-Tolylureido)phenyl)-1 ,2,4-oxadiazol-5-yl)cyclohexane carboxylic acid;

(1 r,4r)-Methyl 4-(3-(4-(3-(3-chlorophenyl)ureido)phenyl)-1 ,2,4-oxadiazol-5-yl) cyclo hexanecarboxylate;

(1 r,4r)-4-(3-(4-(3-(3-Chlorophenyl)ureido)phenyl)-1 ,2,4-oxadiazol-5-yl)cyclo hexanecarboxylic acid;

(1 r,4r)-Methyl 4-(3-(4-(3-(4-chloro-2-phenoxyphenyl)ureido)phenyl)-1 ,2,4-oxadiazol-5- yl)cyclohexanecarboxylate; (1 r,4r)-4-(3-(4-(3-(4-Chloro-2-phenoxyphenyl)ureido)phenyl)-1 ,2,4-oxadiazol-5-yl) cyclohexanecarboxylic acid;

(1 r,4r)-Methyl 4-(3-(4-(4-tert-butylbenzamido)phenyl)-1 ,2,4-oxadiazol-5-yl)

cyclohexanecarboxylate;

(1 r,4r)-4-(3-(4-(4-t-Butylbenzamido)phenyl)-1 ,2,4-oxadiazol-5-yl)cyclohexane carboxylic acid;

(1 r,4r)-Methyl 4-(3-(4-biphenyl-4-ylcarboxamidophenyl)-1 ,2,4-oxadiazol-5-yl) cyclohexanecarboxylate;

(1 r,4r)-4-(3-(4-Biphenyl-4-ylcarboxamidophenyl)-1 ,2,4-oxadiazol-5-yl)cyclo

hexanecarboxylic acid;

(1 r,4r)-Methyl 4-(3-(4-(4-(trifluoromethoxy)benzamido)phenyl)-1 ,2,4-oxadiazol -5- yl)cyclohexanecarboxylate;

(1 r,4r)-4-(3-(4-(4-(Trifluoromethoxy)benzamido)phenyl)-1 ,2,4-oxadiazol-5-yl)

cyclohexanecarboxylic acid;

Methyl 4-(5-(4-(3-(3,5-difluorophenyl)ureido)phenyl)thiazol-2-yl)-2,2-dimethyl butanoate; 4-(5-(4-(3-(3,5-Difluorophenyl)ureido)phenyl)thiazol-2-yl)-2,2-dimethylbutanoic acid; Sodium salt of 4-(5-(4-(3-(3,5-difluorophenyl)ureido)phenyl)thiazol-2-yl)-2,2- dimethylbutanoate;

Methyl 2,2-dimethyl-4-(5-(4-(3-(2,4,5-trifluorophenyl)ureido)phenyl)thiazol-2-yl) butanoate;

2,2-Dimethyl-4-(5-(4-(3-(2,4,5-trifluorophenyl)ureido)phenyl)thiazol-2-yl)butanoic acid; Sodium salt of 2,2-dimethyl-4-(5-(4-(3-(2,4,5-trifluorophenyl)ureido)phenyl) thiazol-2- yl)butanoate;

Methyl 2,2-dimethyl-4-(5-(4-(piperidine-1 -carboxamido)phenyl)thiazol-2-yl) butanoate; 2,2-Dimethyl-4-(5-(4-(piperidine-1 -carboxamido)phenyl)thiazol-2-yl)butanoic acid;

Methyl 2,2-dimethyl-4-(5-(4-(morpholine-4-carboxamido)phenyl)thiazol-2-yl) butanoate; 2,2-Dimethyl-4-(5-(4-(morpholine-4-carboxamido)phenyl)thiazol-2-yl)butanoic acid; Methyl 2,2-dimethyl-4-(5-(4-(4-methylpiperazine-1 -carboxamido)phenyl)thiazol-2- yl)butanoate;

2,2-Dimethyl-4-(5-(4-(4-methylpiperazine-1 -carboxamido)phenyl)thiazol-2-yl) butanoic acid hydrochloride;

Methyl 4-(5-(4-(3-(2,3-dihydrobenzo[b][1 ,4]dioxin-6-yl)ureido)phenyl)thiazol-2-yl)-2,2- dimethylbutanoate; 4-(5-(4-(3-(2,3-Dihydrobenzo[b][1 ,4]dioxin-6-yl)ureido)phenyl)thiazol-2-yl)-2,2- dimethylbutanoic acid;

Methyl 4-(5-(4-(3-(1 H-tetrazol-5-yl)ureido)phenyl)thiazol-2-yl)-2,2-dimethyl butanoate; 4-(5-(4-(3-(1 H-Tetrazol-5-yl)ureido)phenyl)thiazol-2-yl)-2,2-dimethylbutanoic acid;

Methyl 4-(5-(4-(3-(2-methoxyethyl)ureido)phenyl)thiazol-2-yl)-2,2-dimethyl butanoate; 4-(5-(4-(3-(2-Methoxyethyl)ureido)phenyl)thiazol-2-yl)-2,2-dimethylbutanoic acid;

Methyl 4-(5-(4-(3-(2,3-dihydro-1 H-inden-2-yl)ureido)phenyl)thiazol-2-yl)-2,2- dimethylbutanoate;

4-(5-(4-(3-(2,3-Dihydro-1 H-inden-2-yl)ureido)phenyl)thiazol-2-yl)-2,2-dimethyl butanoic acid;

Methyl 4-(5-(4-(3-cyclohexyl-3-methylureido)phenyl)thiazol-2-yl)-2,2-dimethyl butanoate;

4-(5-(4-(3-Cyclohexyl-3-methylureido)phenyl)thiazol-2-yl)-2,2-dimethylbutanoic acid; Methyl 2,2-dimethyl-4-(5-(4-(3-(3,4,5-trifluorophenyl)ureido)phenyl)thiazol-2-yl) butanoate;

2,2-Dimethyl-4-(5-(4-(3-(3,4,5-trifluorophenyl)ureido)phenyl)thiazol-2-yl)butanoic acid; Sodium salt of 2,2-dimethyl-4-(5-(4-(3-(3,4,5-trifluorophenyl) ureido) phenyl) thiazol-2- yl)butanoate;

Methyl 2,2-dimethyl-4-(5-(4-(3-(2-(piperidin-1 -yl)ethyl)ureido)phenyl)thiazol-2-yl) butanoate;

2,2-Dimethyl-4-(5-(4-(3-(2-(piperidin-1 -yl)ethyl)ureido)phenyl)thiazol-2-yl) butanoic acid; Methyl 4-(5-(4-(3-benzylureido)phenyl)thiazol-2-yl)-2,2-dimethylbutanoate;

4-(5-(4-(3-Benzylureido)phenyl)thiazol-2-yl)-2,2-dimethylbutanoic acid;

Methyl 4-(5-(4-(4,4-difluoropiperidine-1 -carboxamido)phenyl)thiazol-2-yl)-2,2- dimethylbutanoate;

4-(5-(4-(4,4-Difluoropiperidine-1 -carboxamido)phenyl)thiazol-2-yl)-2,2-dimethylbutanoic acid;

Methyl 2,2-dimethyl-4-(5-(4-(4-phenylpiperidine-1 -carboxamido)phenyl)thiazol-2- yl)butanoate;

2,2-Dimethyl-4-(5-(4-(4-phenylpiperidine-1 -carboxamido)phenyl)thiazol-2-yl) butanoic acid;

Methyl 2,2-dimethyl-4-(5-(4-(4-phenylpiperidine-1 -carboxamido)phenyl)thiazol-2- yl)butanoate;

4-(5-(4-(3-(4-Cyanobenzyl)ureido)phenyl)thiazol-2-yl)-2,2-dimethylbutanoic acid; Methyl 4-(5-(4-(3-(2-fluorophenyl)thioureido)phenyl)thiazol-2-yl)-2,2-dimethyl butanoate; 4-(5-(4-(3-(2-Fluorophenyl)thioureido)phenyl)thiazol-2-yl)-2,2-dimethylbutanoic acid; Methyl 4-(5-(4-(3-(2-fluorophenyl)guanidino)phenyl)thiazol-2-yl)-2,2-dimethyl butanoate; 4-(5-(4-(3-(2-Fluorophenyl)guanidino)phenyl)thiazol-2-yl)-2,2-dimethylbutanoic acid; Methyl 4-(5-(4-(3-(2-fluorophenyl)-2-methylguanidino)phenyl)thiazol-2-yl)-2,2- dimethylbutanoate;

4-(5-(4-(3-(2-Fluorophenyl)-2-methylguanidino)phenyl)thiazol-2-yl)-2,2-dimethylbutanoic acid;

Methyl 4-(5-(4-(2-cyano-3-(2-fluorophenyl)guanidino)phenyl)thiazol-2-yl)-2,2- dimethylbutanoate;

4-(5-(4-(2-Cyano-3-(2-fluorophenyl)guanidino)phenyl)thiazol-2-yl)-2,2-dimethyl butanoic acid;

Methyl 4-(5-(4-(3-(3-(trifluoromethyl)phenyl)ureido)phenyl)-1 ,3,4-thiadiazol-2-yl) butanoate;

4-(5-(4-(3-(3-(Trifluoromethyl)phenyl)ureido)phenyl)-1 ,3,4-thiadiazol-2-yl) butanoic acid; Methyl 4-(5-(4-(3-(2-chlorophenyl)ureido)phenyl)-1 ,3,4-thiadiazol-2-yl)butanoate;

4-(5-(4-(3-(2-Chlorophenyl)ureido)phenyl)-1 ,3,4-thiadiazol-2-yl)butanoic acid;

Methyl 4-(5-(4-(3-(p-tolyl)ureido)phenyl)-1 ,3,4-thiadiazol-2-yl)butanoate;

4-(5-(4-(3-(p-Tolyl)ureido)phenyl)-1 ,3,4-thiadiazol-2-yl)butanoic acid;

Methyl 4-(5-(4-(3-(2,4-difluorophenyl)ureido)phenyl)-1 ,3,4-thiadiazol-2-yl) butanoate; 4-(5-(4-(3-(2,4-Difluorophenyl)ureido)phenyl)-1 ,3,4-thiadiazol-2-yl)butanoic acid;

Methyl 4-(5-(4-(3-(4-chloro-2-phenoxyphenyl)ureido)phenyl)-1 ,3,4-thiadiazol-2-yl) butanoate;

4-(5-(4-(3-(4-Chloro-2-phenoxyphenyl)ureido)phenyl)-1 ,3,4-thiadiazol-2-yl) butanoic acid;

Methyl 4-(5-(4-(4-(tert-butyl)benzamido)phenyl)-1 ,3,4-thiadiazol-2-yl)butanoate;

4-(5-(4-(4-(t-Butyl)benzamido)phenyl)-1 ,3,4-thiadiazol-2-yl)butanoic acid;

Methyl 4-(5-(4-([1 ,1 '-biphenyl]-4-ylcarboxamido)phenyl)-1 ,3,4-thiadiazol-2-yl) butanoate;

4-(5-(4-([1 ,1 '-Biphenyl]-4-ylcarboxamido)phenyl)-1 ,3,4-thiadiazol-2-yl)butanoic acid; Methyl 4-(5-(4-(4-(trifluoromethoxy)benzamido)phenyl)-1 ,3,4-thiadiazol-2-yl) butanoate; 4-(5-(4-(4-(trifluoromethoxy)benzamido)phenyl)-1 ,3,4-thiadiazol-2-yl)butanoic acid; Methyl 4-(5-(4-(3-(2-chlorophenyl)ureido)phenyl)-1 ,3,4-oxadiazol-2-yl)butanoate;

4-(5-(4-(3-(2-Chlorophenyl)ureido)phenyl)-1 ,3,4-oxadiazol-2-yl)butanoic acid; Methyl 4-(5-(4-(3-(m-tolyl)ureido)phenyl)-1 ,3,4-oxadiazol-2-yl)butanoate;

4-(5-(4-(3-(m-Tolyl)ureido)phenyl)-1 ,3,4-oxadiazol-2-yl)butanoic acid;

Methyl 4-(5-(4-(3-(2,4-difluorophenyl)ureido)phenyl)-1 ,3,4-oxadiazol-2-yl) butanoate;

4-(5-(4-(3-(2,4-Difluorophenyl)ureido)phenyl)-1 ,3,4-oxadiazol-2-yl)butanoic acid;

Methyl 4-(5-(4-(3-(3-(trifluoromethyl)phenyl)ureido)phenyl)-1 ,3,4-oxadiazol-2-yl) butanoate;

4-(5-(4-(3-(3-(Trifluoromethyl)phenyl)ureido)phenyl)-1 ,3,4-oxadiazol-2-yl) butanoic acid; Ethyl 4-(3-(4-(3-(2-chlorophenyl)ureido)phenyl)-1 H-pyrazol-1 -yl)cyclohexane carboxylate;

4-(3-(4-(3-(2-Chlorophenyl)ureido)phenyl)-1 H-pyrazol-1 -yl) cyclohexane carboxylic acid;

Ethyl 4-(3-(4-(3-(2-fluorophenyl)ureido)phenyl)-1 H-pyrazol-1 -yl)cyclohexane

carboxylate;

4-(3-(4-(3-(2-Fluorophenyl)ureido)phenyl)-1 H-pyrazol-1 -yl)cyclohexane carboxylic acid; Ethyl 4-(3-(4-(3-(2,4-difluorophenyl)ureido)phenyl)-1 H-pyrazol-1 -yl)cyclohexane carboxylate;

4-(3-(4-(3-(2,4-Difluorophenyl)ureido)phenyl)-1 H-pyrazol-1 -yl)cyclohexane carboxylic acid;

Ethyl 4-(3-(4-(3-(3-(trifluoromethyl)phenyl)ureido)phenyl)-1 H-pyrazol-1 -yl)

cyclohexanecarboxylate;

4-(3-(4-(3-(3-(Trifluoromethyl)phenyl)ureido)phenyl)-1 H-pyrazol-1 -yl)

cyclohexanecarboxylic acid;

Ethyl 4-(3-(4-(3-(m-tolyl)ureido)phenyl)-1 H-pyrazol-1 -yl)cyclohexane carboxylate;

4-(3-(4-(3-(m-Tolyl)ureido)phenyl)-1 H-pyrazol-1 -yl)cyclohexanecarboxylic acid;

Methyl 4-(3-(4-(3-(4-chloro-2-phenoxyphenyl)ureido)phenyl)-1 ,2,4-oxadiazol-5-yl) butanoate;

4-(3-(4-(3-(4-Chloro-2-phenoxyphenyl)ureido)phenyl)-1 ,2,4-oxadiazol-5-yl) butanoic acid;

Methyl 4-(3-(4-(3-(2,4-difluorophenyl)ureido)phenyl)-1 ,2,4-oxadiazol-5-yl) butanoate; 4-(3-(4-(3-(2,4-Difluorophenyl)ureido)phenyl)-1 ,2,4-oxadiazol-5-yl)butanoic acid;

Methyl 4-(3-(4-(3-(2-chlorophenyl)ureido)phenyl)-1 ,2,4-oxadiazol-5-yl)butanoate;

4-(3-(4-(3-(2-Chlorophenyl)ureido)phenyl)-1 ,2,4-oxadiazol-5-yl)butanoic acid;

Methyl 4-(3-(4-(3-(4-chloro-2-phenoxyphenyl)ureido)phenyl)-1 ,2,4-oxadiazol-5-yl) butanoate; 4-(3-(4-(3-(4-Chloro-2-phenoxyphenyl)ureido)phenyl)-1 ,2,4-oxadiazol-5-yl) butanoic acid;

Methyl 4-(3-(4-(3-(2,4-difluorophenyl)ureido)phenyl)-1 ,2,4-oxadiazol-5-yl) butanoate; 4-(3-(4-(3-(2,4-Difluorophenyl)ureido)phenyl)-1 ,2,4-oxadiazol-5-yl)butanoic acid;

Methyl 4-(3-(4-(3-(2-chlorophenyl)ureido)phenyl)-1 ,2,4-oxadiazol-5-yl)butanoate;

4-(3-(4-(3-(2-Chlorophenyl)ureido)phenyl)-1 ,2,4-oxadiazol-5-yl)butanoic acid;

Methyl 4-(3-(4-(4-fluorobenzamido)phenyl)-1 ,2,4-oxadiazol-5-yl)-2,2-dimethyl butanoate;

4-(3-(4-(4-Fluorobenzamido)phenyl)-1 ,2,4-oxadiazol-5-yl)-2,2-dimethylbutanoic acid; Methyl 4-(3-(4-([1 ,1 '-biphenyl]-4-ylcarboxamido)phenyl)-1 ,2,4-oxadiazol-5-yl)-2,2- dimethylbutanoate;

4-(3-(4-([1 ,1 '-Biphenyl]-4-ylcarboxamido)phenyl)-1 ,2,4-oxadiazol-5-yl)-2,2- dimethylbutanoic acid;

t-Butyl 2-(4-(5-(4-(3-(2-chlorophenyl)ureido)phenyl)thiazol-2-yl)cyclohexyl) acetate; 2-(4-(5-(4-(3-(2-Chlorophenyl)ureido)phenyl)thiazol-2-yl)cyclohexyl)acetic acid;

t-Butyl 2-(4-(5-(4-(3-(2-fluorophenyl)ureido)phenyl)thiazol-2-yl)cyclohexyl) acetate; 2-(4-(5-(4-(3-(2-Fluorophenyl)ureido)phenyl)thiazol-2-yl)cyclohexyl)acetic acid;

Ethyl 2-(4-(5-(4-(3-(3,5-difluorophenyl)ureido)phenyl)thiazol-2-yl) cyclohexyl) acetate; 2-(4-(5-(4-(3-(3,5-Difluorophenyl)ureido)phenyl)thiazol-2-yl)cyclohexyl)acetic acid; Ethyl 2-(4-(5-(4-(3-(2,4,5-trifluorophenyl)ureido)phenyl)thiazol-2-yl)cyclohexyl) acetate; 2-(4-(5-(4-(3-(2,4,5-Trifluorophenyl)ureido)phenyl)thiazol-2-yl)cyclohexyl)acetic acid; Ethyl 2-(4-(5-(4-(3-(2,4,6-trifluorophenyl)ureido)phenyl)thiazol-2-yl)cyclohexyl) acetate; 2-(4-(5-(4-(3-(2,4,6-Trifluorophenyl)ureido)phenyl)thiazol-2-yl)cyclohexyl)acetic acid; Ethyl 2-(4-(5-(4-(3-(2,4-difluorophenyl)ureido)phenyl)thiazol-2-yl)cyclohexyl) acetate; 2-(4-(5-(4-(3-(2,4-Difluorophenyl)ureido)phenyl)thiazol-2-yl)cyclohexyl)acetic acid; Ethyl 2-(4-(5-(4-(2,4-dichlorobenzamido)phenyl)thiazol-2-yl)cyclohexyl)acetate;

2-(4-(5-(4-(2,4-Dichlorobenzamido)phenyl)thiazol-2-yl)cyclohexyl)acetic acid;

Ethyl 2-(4-(5-(4-(2-fluoro-6-(trifluoromethyl)benzamido)phenyl)thiazol-2-yl) cyclohexyl) acetate;

2-(4-(5-(4-(2-Fluoro-6-(trifluoromethyl)benzamido)phenyl)thiazol-2-yl) cyclohexyl)acetic acid;

Ethyl 2-(4-(5-(4-(3-(3,4,5-trifluorophenyl)ureido)phenyl)thiazol-2-yl)cyclohexyl) acetate; 2-(4-(5-(4-(3-(3,4,5-Trifluorophenyl)ureido)phenyl)thiazol-2-yl)cyclohexyl)acetic acid; Ethyl 2-(4-(5-(4-(2-phenyl-5-(trifluoromethyl)oxazole-4-carboxamido)phenyl) thiazol-2- yl)cyclohexyl)acetate;

2-(4-(5-(4-(2-Phenyl-5-(trifluoromethyl)oxazole-4-carboxamido)phenyl)thiazol-2- yl)cyclohexyl)acetic acid;

Ethyl 2-(4-(5-(4-(5-methyl-2-phenyloxazole-4-carboxamido)phenyl)thiazol-2-yl) cyclohexyl)acetate;

2-(4-(5-(4-(5-Methyl-2-phenyloxazole-4-carboxamido)phenyl)thiazol-2-yl)

cyclohexyl)acetic acid;

Ethyl 2-(4-(5-(4-(3-(2-fluorophenyl)thioureido)phenyl)thiazol-2-yl)cyclohexyl) acetate; 2-(4-(5-(4-(3-(2-Fluorophenyl)thioureido)phenyl)thiazol-2-yl)cyclohexyl)acetic acid; Ethyl 2-(4-(5-(4-(3-(2-fluorophenyl)guanidino)phenyl)thiazol-2-yl)cyclohexyl) acetate; 4-(2-(4-((5-Methyl-1 ,3,4-oxadiazol-2-yl)methyl)cyclohexyl)thiazol-5-yl)aniline;

1 -(2,4-Difluorophenyl)-3-(4-(2-(4-((5-methyl-1 ,3,4-oxadiazol-2-yl)methyl)

cyclohexyl)thiazol-5-yl)phenyl)urea;

1 -(2-Chlorophenyl)-3-(4-(2-(4-((5-methyl-1 ,3,4-oxadiazol-2-yl)methyl) cyclohexyl) thiazol-5-yl)phenyl)urea;

1 -(3,5-Difluorophenyl)-3-(4-(2-(4-((5-methyl-1 ,3,4-oxadiazol-2-yl)methyl)

cyclohexyl)thiazol-5-yl)phenyl)urea;

1 -(4-(2-(4-((5-Methyl-1 ,3,4-oxadiazol-2-yl)methyl)cyclohexyl)thiazol-5-yl) phenyl)-3- (2,4,5-trifluorophenyl)urea;

1 -(4-(2-(4-((5-Methyl-1 ,3,4-oxadiazol-2-yl)methyl)cyclohexyl)thiazol-5-yl)phenyl)-3- (2,4,6-trifluorophenyl)urea;

1 -(4-(2-(4-((5-Methyl-1 ,3,4-oxadiazol-2-yl)methyl)cyclohexyl)thiazol-5-yl)phenyl)-3- phenylurea;

2,6-Difluoro-N-(4-(2-(4-((5-methyl-1 ,3,4-oxadiazol-2-yl)methyl)cyclohexyl) thiazol-5 yl)phenyl)benzamide;

4- (2-(4-((3-Methyl-1 ,2,4-oxadiazol-5-yl)methyl)cyclohexyl)thiazol-5-yl)aniline;

1 -(2-Chlorophenyl)-3-(4-(2-(4-((3-methyl-1 ,2,4-oxadiazol-5-yl)methyl)cyclohexyl) thiazol-5-yl)phenyl)urea;

1 -(2-Fluorophenyl)-3-(4-(2-(4-((3-methyl-1 ,2,4-oxadiazol-5-yl)methyl)cyclohexyl) thiazol

5- yl)phenyl)urea;

1 -(3,5-Difluorophenyl)-3-(4-(2-(4-((3-methyl-1 ,2,4-oxadiazol-5-yl)methyl)

cyclohexyl)thiazol-5-yl)phenyl)urea; 1 -(4-(2-(4-((3-Methyl-1 ,2,4-oxadiazol-5-yl)methyl)cyclohexyl)thiazol-5-yl)phenyl) -3- (2,4,5-trifluorophenyl)urea;

1 - (2,4-Difluorophenyl)-3-(4-(2-(4-((3-methyl-1 ,2,4-oxadiazol-5-yl)methyl)

cyclohexyl)thiazol-5-yl)phenyl)urea;

1 -(4-(2-(4-((3-Methyl-1 ,2,4-oxadiazol-5-yl)methyl)cyclohexyl)thiazol-5-yl) phenyl)-3- phenylurea;

2, 6-Difluoro-N-(4-(2-(4-((3-methyl-1 ,2,4-oxadiazol-5-yl)methyl)cyclohexyl) thiazol-5- yl)phenyl)benzamide;

2- Chloro-N-(4-(2-(4-((3-methyl-1 ,2,4-oxadiazol-5-yl)methyl)cyclohexyl)thiazol-5- yl)phenyl)benzamide;

3, 5-Difluoro-N-(4-(2-(4-((3-methyl-1 , 2, 4-oxadiazol-5-yl)methyl) cyclohexyl) thiazol-5- yl)phenyl)benzamide;

N-Acetyl-2-(4-(5-(4-aminophenyl)thiazol-2-yl)cyclohexyl)acetamide;

N-Acetyl-2-(4-(5-(4-(3-(2-chlorophenyl)ureido)phenyl)thiazol-2-yl)cyclohexyl) acetamide;

N-Acetyl-2-(4-(5-(4-(3-(2,4-difluorophenyl)ureido)phenyl)thiazol-2-yl)

cyclohexyl)acetamide;

N-Acetyl-2-(4-(5-(4-(3-(2,4,5-trifluorophenyl)ureido)phenyl)thiazol-2-yl)

cyclohexyl)acetamide;

N-(4-(2-(4-(2-Acetamido-2-oxoethyl)cyclohexyl)thiazol-5-yl)phenyl)-2,6-difluoro benzamide;

1 -(2-Chlorophenyl)-3-(4-(2-(4-(2-hydroxypropan-2-yl)cyclohexyl)thiazol-5-yl) phenyl)urea;

1 -(3,5-Difluorophenyl)-3-(4-(2-(4-(2-hydroxypropan-2-yl)cyclohexyl)thiazol-5-yl) phenyl)urea;

1 -(2,4-Difluorophenyl)-3-(4-(2-(4-(2-hydroxypropan-2-yl)cyclohexyl)thiazol-5-yl) phenyl)urea;

1 -(2,4-Difluorophenyl)-3-(4-(2-(4-(2-hydroxy-2-methylpropyl)cyclohexyl) thiazol-5- yl)phenyl)urea;

1 -(3,5-Difluorophenyl)-3-(4-(2-(4-(2-hydroxy-2-methylpropyl)cyclohexyl)thiazol-5- yl)phenyl)urea;

1 -(4-(2-(4-(2-Hydroxy-2-methylpropyl)cyclohexyl)thiazol-5-yl)phenyl)-3-(2,4,5- trifluorophenyl)urea; 1 - (3,5-Difluorophenyl)-3-(4-(2-(4-(2-hydrazinyl-2-oxoethyl)cyclohexyl)thiazol-5- yl)phenyl)urea;

4-(2-(4-((5-Methyl-1 ,3,4-thiadiazol-2-yl)methyl)cyclohexyl)thiazol-5-yl)aniline;

1 -(4-(2-(4-((5-Methyl-1 ,3,4-thiadiazol-2-yl)methyl)cyclohexyl)thiazol-5-yl)phenyl) -3-

(2,4,5-trifluorophenyl)urea;

Ethyl 2-(4-(4-(4-(3-(2-fluorophenyl)ureido)phenyl)thiazol-2-yl)piperidin-1 -yl) acetate;

2- (4-(4-(4-(3-(2-Fluorophenyl)ureido)phenyl)thiazol-2-yl)piperidin-1 -yl)acetic acid;

Ethyl 2-(4-(4-(4-(3-(2-chlorophenyl)ureido)phenyl)thiazol-2-yl)piperidin-1 -yl) acetate; 2-(4-(4-(4-(3-(2-Chlorophenyl)ureido)phenyl)thiazol-2-yl)piperidin-1 -yl)acetic acid;

Ethyl 2-(4-(5-(4-(3-(2-chlorophenyl)ureido)phenyl)thiazol-2-yl)piperidin-1 -yl) acetate; 2-(4-(5-(4-(3-(2-Chlorophenyl)ureido)phenyl)thiazol-2-yl)piperidin-1 -yl)acetic acid;

Ethyl 2-(4-(5-(4-(3-(2-fluorophenyl)ureido)phenyl)thiazol-2-yl)piperidin-1 -yl) acetate; 2-(4-(5-(4-(3-(2-Fluorophenyl)ureido)phenyl)thiazol-2-yl)piperidin-1 -yl)acetic acid;

Ethyl 2-(4-(5-(4-(3-(2,4-difluorophenyl)ureido)phenyl)thiazol-2-yl)piperidin-1 -yl) acetate; 2-(4-(5-(4-(3-(2,4-Difluorophenyl)ureido)phenyl)thiazol-2-yl)piperidin-1 -yl)acetic acid; Ethyl 2-(4-(5-(4-(3-(2,4,5-trifluorophenyl)ureido)phenyl)thiazol-2-yl)piperidin-1 -yl) acetate;

2-(4-(5-(4-(3-(2,4,5-Trifluorophenyl)ureido)phenyl)thiazol-2-yl)piperidin-1 -yl) acetic acid;

Ethyl 2-(4-(5-(4-(3-(2-(trifluoromethyl)phenyl)ureido)phenyl)thiazol-2-yl) piperidin-1 - yl)acetate;

2-(4-(5-(4-(3-(2-(Trifluoromethyl)phenyl)ureido)phenyl)thiazol-2-yl)piperidin-1 -yl) acetic acid;

Ethyl 2-(4-(5-(4-(3-(2,3,4-trifluorophenyl)ureido)phenyl)thiazol-2-yl)piperidin-1 -yl) acetate;

2-(4-(5-(4-(3-(2,3,4-Trifluorophenyl)ureido)phenyl)thiazol-2-yl)piperidin-1 -yl) acetic acid; Ethyl 2-(4-(5-(4-(3-(2,4,6-trifluorophenyl)ureido)phenyl)thiazol-2-yl)piperidin-1 -yl) acetate;

2-(4-(5-(4-(3-(2,4,6-Trifluorophenyl)ureido)phenyl)thiazol-2-yl)piperidin-1 -yl) acetic acid; Ethyl 2-methyl-2-(4-(5-(4-(3-(2,4,5-trifluorophenyl)ureido)phenyl)thiazol-2-yl) piperidin- 1 -yl)propanoate;

Ethyl 2-(4-(5-(4-(3-(2-fluorophenyl)ureido)phenyl)thiazol-2-yl)piperidin-1 -yl)-2- methylpropanoate; Ethyl 2-(4-(5-(4-(3-(2-chlorophenyl)ureido)phenyl)thiazol-2-yl)piperidin-1 -yl)-2- methylpropanoate;

Ethyl 2-(4-(5-(4-(3-(2,4-difluorophenyl)ureido)phenyl)thiazol-2-yl)piperidin-1 -yl)-2- methylpropanoate;

t-Butyl 2-(4-(5-(4-(3-(2,4,5-trifluorophenyl)ureido)phenyl)thiazol-2-yl)piperidin-1 - yl)propanoate;

2-(4-(5-(4-(3-(2,4,5-Trifluorophenyl)ureido)phenyl)thiazol-2-yl)piperidin-1 -yl) propanoic acid;

t-Butyl 2-(4-(5-(4-(3-(2-fluorophenyl)ureido)phenyl)thiazol-2-yl)piperidin-1 -yl) propanoate;

2-(4-(5-(4-(3-(2-Fluorophenyl)ureido)phenyl)thiazol-2-yl)piperidin-1 -yl)propanoic acid; t-Butyl 2-(4-(5-(4-(3-(2-chlorophenyl)ureido)phenyl)thiazol-2-yl)piperidin-1 -yl) propanoate;

2-(4-(5-(4-(3-(2-Chlorophenyl)ureido)phenyl)thiazol-2-yl)piperidin-1 -yl) propanoic acid; t-Butyl 2-(4-(5-(4-(3-(2,4-difluorophenyl)ureido)phenyl)thiazol-2-yl)piperidin-1 -yl) propanoate;

2-(4-(5-(4-(3-(2,4-Difluorophenyl)ureido)phenyl)thiazol-2-yl)piperidin-1 -yl) propanoic acid;

t-Butyl 2-(4-(5-(4-(3-(2,4,6-trifluorophenyl)ureido)phenyl)thiazol-2-yl)piperidin-1 -yl) propanoate;

2-(4-(5-(4-(3-(2,4,6-Trifluorophenyl)ureido)phenyl)thiazol-2-yl)piperidin-1 -yl) propanoic acid;

t-Butyl 2-methyl-2-(4-(5-(4-(3-(2,4,5-trifluorophenyl)ureido)phenyl)thiazol-2-yl) piperidin-

1 - yl)propanoate;

2- Methyl-2-(4-(5-(4-(3-(2,4,5-trifluorophenyl)ureido)phenyl)thiazol-2-yl) piperidin-1 - yl)propanoic acid;

t-Butyl 2-(4-(5-(4-(3-(2-fluorophenyl)ureido)phenyl)thiazol-2-yl)piperidin-1 -yl)-2- methylpropanoate;

2-(4-(5-(4-(3-(2-Fluorophenyl)ureido)phenyl)thiazol-2-yl)piperidin-1 -yl)-2- methylpropanoic acid;

t-Butyl 2-(4-(5-(4-(3-(2-chlorophenyl)ureido)phenyl)thiazol-2-yl)piperidin-1 -yl)-2- methylpropanoate;

2-(4-(5-(4-(3-(2-Chlorophenyl)ureido)phenyl)thiazol-2-yl)piperidin-1 -yl)-2-methyl propanoic acid; t-Butyl 2-(4-(5-(4-(3-(2,4-difluorophenyl)ureido)phenyl)thiazol-2-yl)piperidin-1 -yl)-2- methylpropanoate;

2-(4-(5-(4-(3-(2,4-Difluorophenyl)ureido)phenyl)thiazol-2-yl)piperidin-1 -yl)-2- methylpropanoic acid;

t-Butyl 2-methyl-2-(4-(5-(4-(3-(2,4,6-trifluorophenyl)ureido)phenyl)thiazol-2-yl) piperidin-

1 - yl)propanoate;

2- Methyl-2-(4-(5-(4-(3-(2,4,6-trifluorophenyl)ureido)phenyl)thiazol-2-yl) piperidin-1 - yl)propanoic acid;

t-Butyl 4-(5-(4-(3-(2-chlorophenyl)ureido)phenyl)thiazol-2-yl)piperidine-1 -carboxylate; 1 -(2-Chlorophenyl)-3-(4-(2-(piperidin-4-yl)thiazol-5-yl)phenyl)urea hydrochloride;

t-Butyl 4-(5-(4-(3-(2-fluorophenyl)ureido)phenyl)thiazol-2-yl)piperidine-1 -carboxylate; 1 -(2-Fluorophenyl)-3-(4-(2-(piperidin-4-yl)thiazol-5-yl)phenyl)urea hydrochloride;

t-Butyl 4-(5-(4-(3-(2,4-difluorophenyl)ureido)phenyl)thiazol-2-yl)piperidine-1 - carboxylate;

1 -(2,4-Difluorophenyl)-3-(4-(2-(piperidin-4-yl)thiazol-5-yl)phenyl)urea hydrochloride; t-Butyl 4-(5-(4-(3-(2,4,6-trifluorophenyl)ureido)phenyl)thiazol-2-yl)piperidine-1 - carboxylate;

1 -(4-(2-(Piperidin-4-yl)thiazol-5-yl)phenyl)-3-(2,4,5-trifluorophenyl)urea hydrochloride;

1 -(2-Fluorophenyl)-3-(4-(2-(1 -((trifluoromethyl)sulfonyl)piperidin-4-yl)thiazol-5-yl) phenyl)urea;

1 -(2-Chlorophenyl)-3-(4-(2-(1 -((trifluoromethyl)sulfonyl)piperidin-4-yl)thiazol-5-yl) phenyl)urea;

1 -(2,4-Difluorophenyl)-3-(4-(2-(1 -((trifluoromethyl)sulfonyl)piperidin-4-yl)thiazol-5- yl)phenyl)urea;

1 -(4-(2-(1 -((Trifluoromethyl)sulfonyl)piperidin-4-yl)thiazol-5-yl)phenyl)-3-(2,4,6- trifluorophenyl)urea;

1 -(4-(2-(1 -((Trifluoromethyl)sulfonyl)piperidin-4-yl)thiazol-5-yl)phenyl)-3-(2,4,5- trifluorophenyl)urea;

1 -(2-Chlorophenyl)-3-(4-(2-(1 -(methylsulfonyl)piperidin-4-yl)thiazol-5-yl)phenyl) urea; 1 -(2-Fluorophenyl)-3-(4-(2-(1 -(methylsulfonyl)piperidin-4-yl)thiazol-5-yl)phenyl) urea; 1 -(2,4-Difluorophenyl)-3-(4-(2-(1 -(methylsulfonyl)piperidin-4-yl)thiazol-5-yl) phenyl)urea; 1 -(4-(2-(1 -(Methylsulfonyl)piperidin-4-yl)thiazol-5-yl)phenyl)-3-(2,4,6-trifluoro

phenyl)urea; 1 -(4-(2-(1 -(Methylsulfonyl)piperidin-4-yl)thiazol-5-yl)phenyl)-3-(2,4,5-trifluoro

phenyl)urea;

Methyl 3-(5-(4-(3-(2-chlorophenyl)ureido)phenyl)thiazol-2-yl)adamantane-1 -carboxylate; 3-(5-(4-(3-(2-Chlorophenyl)ureido)phenyl)thiazol-2-yl)adamantane-1 -carboxylic acid; Methyl 3-(5-(4-(3-(2-fluorophenyl)ureido)phenyl)thiazol-2-yl)adamantane-1 -carboxylate; 3-(5-(4-(3-(2-Fluorophenyl)ureido)phenyl)thiazol-2-yl)adamantane-1 -carboxylic acid; Methyl 3-(5-(4-(3-(2,4-difluorophenyl)ureido)phenyl)thiazol-2-yl)adamantine -1 - carboxylate;

3-(5-(4-(3-(2,4-Difluorophenyl)ureido)phenyl)thiazol-2-yl)adamantane-1 -carboxylic acid; Methyl 3-(5-(4-(3-(2,6-difluorophenyl)ureido)phenyl)thiazol-2-yl)adamantine -1 - carboxylate;

3-(5-(4-(3-(2,6-Difluorophenyl)ureido)phenyl)thiazol-2-yl)adamantane-1 -carboxylic acid; Methyl 3-(5-(4-(3-(2,4,5-trifluorophenyl)ureido)phenyl)thiazol-2-yl) adamantane-1 - carboxylate;

3-(5-(4-(3-(2,4,5-Trifluorophenyl)ureido)phenyl)thiazol-2-yl)adamantane-1 -carboxylic acid;

Methyl 3-(5-(4-(3-(2,3,4-trifluorophenyl)ureido)phenyl)thiazol-2-yl) adamantane-1 - carboxylate;

3-(5-(4-(3-(2,3,4-Trifluorophenyl)ureido)phenyl)thiazol-2-yl)adamantane-1 -carboxylic acid;

Methyl 3-(5-(4-(3-(3,5-difluorophenyl)ureido)phenyl)thiazol-2-yl)adamantane -1 - carboxylate;

3-(5-(4-(3-(3,5-Difluorophenyl)ureido)phenyl)thiazol-2-yl)adamantane-1 -carboxylic acid; Methyl 3-(5-(4-(3-(3-(trifluoromethyl)phenyl)ureido)phenyl)thiazol-2-yl) adamantane-1 - carboxylate;

3-(5-(4-(3-(3-(Trifluoromethyl)phenyl)ureido)phenyl)thiazol-2-yl)adamantane-1 - carboxylic acid;

N-(2-(5-(4-(3-(2-Chlorophenyl)ureido)phenyl)thiazol-2-yl)ethyl)-1 ,1 ,1 -trifluoro

methanesulfonamide;

1 ,1 ,1 -Trifluoro-N-(2-(5-(4-(3-(2-fluorophenyl)ureido)phenyl)thiazol-2-yl)ethyl)

methanesulfonamide;

N-(2-(5-(4-(3-(3,5-Difluorophenyl)ureido)phenyl)thiazol-2-yl)ethyl)-1 ,1 ,1 - trifluoromethanesulfonamide; 1 ,1 ,1 -Trifluoro-N-(2-(5-(4-(3-(2,4,5-trifluorophenyl)ureido)phenyl)thiazol-2-yl) ethyl)methanesulfonamide;

1 ,1 ,1 -Trifluoro-N-(2-(5-(4-(3-(2,4,6-trifluorophenyl)ureido)phenyl)thiazol-2-yl) ethyl)methanesulfonamide;

1 ,1 ,1 -Trifluoro-N-(2-(5-(4-(3-(4-(trifluoromethyl)phenyl)ureido)phenyl)thiazol-2-yl) ethyl)methanesulfonamide;

1 ,1 ,1 -Trifluoro-N-(2-(5-(4-(3-phenylureido)phenyl)thiazol-2-yl)ethyl)methane sulfonamide;

N-(2-(5-(4-(3-Cyclohexylureido)phenyl)thiazol-2-yl)ethyl)-1 ,1 ,1 -trifluoro

methanesulfonamide;

2-Chloro-N-(4-(2-(2-(trifluoromethylsulfonamido)ethyl)thiazol-5-yl)phenyl) benzamide; N-(4-(2-(2-(Trifluoromethylsulfonamido)ethyl)thiazol-5-yl)phenyl) cyclohexane carboxamide;

4-(Trifluoromethyl)-N-(4-(2-(2-(trifluoromethylsulfonamido)ethyl)thiazol-5-yl) phenyl)benzamide;

N-(4-(2-(2-(Trifluoromethylsulfonamido)ethyl)thiazol-5-yl)phenyl)benzamide;

2-Phenyl-5-(trifluoromethyl)-N-(4-(2-(2-(trifluoromethylsulfonamido)ethyl) thiazol-5- yl)phenyl)oxazole-4-carboxamide;

1 ,1 ,1 -Trifluoro-N-(2-(5-(4-(3-(2-fluorophenyl)thioureido)phenyl)thiazol-2-yl) ethyl) methanesulfonamide;

1 ,1 ,1 -Trifluoro-N-(2-(5-(4-(3-(2-fluorophenyl)guanidino)phenyl)thiazol-2-yl) ethyl) methanesulfonamide;

1 ,1 ,1 -Trifluoro-N-(2-(5-(4-(3-(2-fluorophenyl)-2-methylguanidino)phenyl) thiazol-2- yl)ethyl)methanesulfonamide;

N-(2-(5-(4-(2-Cyano-3-(2-fluorophenyl)guanidino)phenyl)thiazol-2-yl)ethyl)-1 ,1 ,1 - trifluoromethanesulfonamide;

N-((5-(4-(3-(2-Chlorophenyl)ureido)phenyl)thiazol-2-yl)methyl)-1 ,1 ,1 -trifluoro methanesulfonamide;

1 ,1 ,1 -Trifluoro-N-((5-(4-(3-(2-fluorophenyl)ureido)phenyl)thiazol-2-yl)methyl) methanesulfonamide;

N-((5-(4-(3-(3,5-Difluorophenyl)ureido)phenyl)thiazol-2-yl)methyl)-1 ,1 ,1 - trifluoromethanesulfonamide;

1 ,1 ,1 -Trifluoro-N-((5-(4-(3-(2,4,5-trifluorophenyl)ureido)phenyl)thiazol-2-yl) methyl)methanesulfonamide; 1 ,1 ,1 -Trifluoro-N-((5-(4-(3-(2,4,6-trifluorophenyl)ureido)phenyl)thiazol-2-yl)

methyl)methanesulfonamide;

N-((5-(4-(3-Cyclohexylureido)phenyl)thiazol-2-yl)methyl)-1 ,1 ,1 -trifluoro

methanesulfonamide;

1 ,1 ,1 -Trifluoro-N-((5-(4-(3-(4-(trifluoromethyl)phenyl)ureido)phenyl)thiazol-2-yl) methyl)methanesulfonamide;

1 ,1 ,1 -Trifluoro-N-((5-(4-(3-phenylureido)phenyl)thiazol-2-yl)methyl)methane sulfonamide;

2-Chloro-N-(4-(2-((trifluoromethylsulfonamido)methyl)thiazol-5-yl)phenyl) benzamide;

4-(Trifluoromethyl)-N-(4-(2-((trifluoromethylsulfonamido)methyl)thiazol-5-yl) phenyl)benzamide;

N-(4-(2-((Trifluoromethylsulfonamido)methyl)thiazol-5-yl)phenyl)benzene sulfonamide;

4-(Trifluoromethyl)-N-(4-(2-((trifluoromethylsulfonamido)methyl)thiazol-5-yl) phenyl)benzenesulfonamide;

N-(4-(2-((Trifluoromethylsulfonamido)methyl)thiazol-5-yl)phenyl) cyclohexane sulfonamide;

2,4-Difluoro-N-(4-(2-((trifluoromethylsulfonamido)methyl)thiazol-5-yl)phenyl) benzenesulfonamide;

N-(2-(5-(4-(3-(2-Chlorophenyl)ureido)phenyl)thiazol-2-yl)propan-2-yl)-1 ,1 ,1 - trifluoromethanesulfonamide;

1 ,1 ,1 -Trifluoro-N-(2-(5-(4-(3-(2-fluorophenyl)ureido)phenyl)thiazol-2-yl) propan-2 yl)methanesulfonamide;

N-(2-(5-(4-(3-(3,5-Difluorophenyl)ureido)phenyl)thiazol-2-yl)propan-2-yl)-1 ,1 ,1 - trifluoromethanesulfonamide;

1 ,1 ,1 -Trifluoro-N-(2-(5-(4-(3-(2,4,5-trifluorophenyl)ureido)phenyl)thiazol-2-yl)propan-2- yl)methanesulfonamide;

1 ,1 ,1 -Trifluoro-N-(2-(5-(4-(3-(2,4,6-trifluorophenyl)ureido)phenyl)thiazol-2-yl) propan-2 yl)methanesulfonamide;

N-(2-(5-(4-(3-Cyclohexylureido)phenyl)thiazol-2-yl)propan-2-yl)-1 ,1 ,1 - trifluoromethanesulfonamide;

N-(4-(2-(2-(Trifluoromethylsulfonamido)propan-2-yl)thiazol-5-yl)phenyl)

benzenesulfonamide;

t-Butyl (2-(5-(4-(3-(2-chlorophenyl)ureido)phenyl)thiazol-2-yl)ethyl) carbamate;

t-Butyl (2-(5-(4-(3-(3,5-difluorophenyl)ureido)phenyl)thiazol-2-yl)ethyl) carbamate; t-Butyl (2-(5-(4-(3-(2,4,5-trifluorophenyl)ureido)phenyl)thiazol-2-yl)ethyl) carbamate; 1 -(4-(2-(2-Aminoethyl)thiazol-5-yl)phenyl)-3-(2-chlorophenyl)urea hydrochloride;

1 -(4-(2-(2-Aminoethyl)thiazol-5-yl)phenyl)-3-(3,5-difluorophenyl)urea hydrochloride; 1 -(4-(2-(2-Aminoethyl)thiazol-5-yl)phenyl)-3-(2,4,5-trifluorophenyl)urea hydrochloride; 4-(5-(4-(3-(2-Chlorophenyl)ureido)phenyl)thiazol-2-yl)-2,2-dimethyl-N- ((trifluoromethyl)sulfonyl)butanamide;

4-(5-(4-(3-(2-Fluorophenyl)ureido)phenyl)thiazol-2-yl)-2,2-dimethyl-N- ((trifluoromethyl)sulfonyl)butanamide;

4-(5-(4-(3-(3,5-Difluorophenyl)ureido)phenyl)thiazol-2-yl)-2,2-dimethyl-N-((trifluoro methyl)sulfonyl)butanamide;

2,2-Dimethyl-N-((trifluoromethyl)sulfonyl)-4-(5-(4-(3-(2,4,5-trifluorophenyl)

ureido)phenyl)thiazol-2-yl)butanamide;

Methyl 4-(5-(4-(3-(2,4,5-trifluorophenyl)ureido)phenyl)thiazol-2-yl)cyclohexane carboxylate;

4-(5-(4-(3-(2,4,5-Trifluorophenyl)ureido)phenyl)thiazol-2-yl)cyclohexanecarboxylic acid;

1 -(4-(2-(4-(2-Hydroxypropan-2-yl)cyclohexyl)thiazol-5-yl)phenyl)-3-(2,4,5- trifluorophenyl)urea;

1 -(4-(2-(4-(2-Aminopropan-2-yl)cyclohexyl)thiazol-5-yl)phenyl)-3-(2,4,5-trifluoro phenyl)urea;

1 -(4-(2-(4-(2-Aminopropan-2-yl)cyclohexyl)thiazol-5-yl)phenyl)-3-(2,4-difluoro phenyl)urea; and

1 -(4-(2-(4-(2-Amino-2-methylpropyl)cyclohexyl)thiazol-5-yl)phenyl)-3-(2,4,5- trifluorophenyl)urea;

or a stereoisomer, tautomer, pharmaceutically acceptable salt, solvate or N-oxide thereof.

25. A pharmaceutical composition comprising a compound of formula 1 according to any of the claims 1 -24, or a stereoisomer, tautomer, pharmaceutically acceptable salt, solvate or N-oxide thereof, and a pharmaceutically acceptable excipient or a carrier.

26. A method of treatment of diacylglycerol acyltransferase 1 (DGAT1 ) mediated disease or disorder comprising administering to a subject in need thereof, a therapeutically effective amount of a compound of formula 1 according to any of the claims 1 -24, or a stereoisomer, tautomer, pharmaceutically acceptable salt, solvate or N-oxide thereof.

27. The method according to claim 26, wherein the DGAT1 mediated disease or disorder is selected from obesity, diabetes, impaired glucose tolerance, diabetic neuropathy, diabetic nephropathy, diabetic retinopathy, anorexia nervosa, bulimia, cachexia, syndrome X, insulin resistance, hypoglycemia, hyperglycemia, hyperuricemia, hyperinsulinemia, hypercholesterolemia, hyperlipidemia, dyslipidemia, mixed dyslipidemia, hypertriglyceridemia, pancreatitis, metabolic acidosis, ketosis, steatosis, dysmetabolic syndrome and nonalcoholic fatty liver disease, skin disorders, acne, atherosclerosis, arteriosclerosis, acute heart failure, congestive heart failure, coronary artery disease, cardiomyopathy, myocardial ischaemia, myocardial infarction, angina pectoris, hypertension, hypotension, stroke, ischemia, ischemic reperfusion injury, aneurysm, restenosis, peripheral vascular disease and vascular stenosis, acne, infertility, polycystic ovary syndrome or Hepatitis C infection.

28. The method according to claim 27, wherein the DGAT1 mediated disease or disorder is selected from impaired glucose tolerance, diabetes, insulin resistance, diabetic neuropathy, diabetic nephropathy, diabetic retinopathy, hypercholesterolemia, hypertriglyceridemia, hyperlipidemia or obesity.

29. The method according to any one of the preceding claims 26 to 28, wherein the DGAT1 mediated disease or disorder is obesity. 30. Use of a compound of formula 1 , according to any one of the claims 1 to 24, or a stereoisomer, tautomer, pharmaceutically acceptable salt, solvate or N-oxide thereof, for the treatment of DGAT1 mediated disease or disorder.

31 . The use according to claim 30, wherein the DGAT1 mediated disease or disorder is selected from obesity, diabetes, impaired glucose tolerance, diabetic neuropathy, diabetic nephropathy, diabetic retinopathy, anorexia nervosa, bulimia, cachexia, syndrome X, insulin resistance, hypoglycemia, hyperglycemia, hyperuricemia, hyperinsulinemia, hypercholesterolemia, hyperlipidemia, dyslipidemia, mixed dyslipidemia, hypertriglyceridemia, pancreatitis, metabolic acidosis, ketosis, steatosis, dysmetabolic syndrome and nonalcoholic fatty liver disease, atherosclerosis, arteriosclerosis, acute heart failure, congestive heart failure, coronary artery disease, cardiomyopathy, myocardial ischaemia, myocardial infarction, angina pectoris, hypertension, hypotension, stroke, ischemia, ischemic reperfusion injury, aneurysm, restenosis, peripheral vascular disease and vascular stenosis, acne, infertility, polycystic ovary syndrome or Hepatitis C infection.

32. The use according to claim 31 , wherein the DGAT1 mediated disease or disorder is selected from obesity, diabetes, insulin resistance, impaired glucose tolerance, diabetic neuropathy, diabetic nephropathy, diabetic retinopathy, hypercholesterolemia, hypertriglyceridemia or hyperlipidemia.

33. The use according to any one of the preceding claims 30 to 32, wherein the DGAT1 mediated disease or disorder is obesity.

34. Use of a compound of formula 1 according to any one of the claims 1 to 24, or a stereoisomer, tautomer, pharmaceutically acceptable salt, solvate or N-oxide thereof, for the manufacture of a medicament for the treatment of diseases or disorders mediated by DGAT1 .

35. A compound of formula D:

Formula D

wherein A, B and Z are as defined in claim 1 for formula 1 ; for use as an intermediate in the preparation of the compound of formula 1 according to any of the claims 1 -24.

36. A process for the preparation of the compound of formula 1 represented by the compound of formula 1 a:

Formula 1 a wherein A, B and Z are as defined in claim 1 for formula 1 ;

the steps comprising:

Step a) treating the compound of formula D:

wherein B and Z are as defined above;

with a compound of formula 8 (i):

A-N=C=0

8 (i)

wherein A is as defined above;

in a solvent selected from tetrahydrofuran (THF) or dichloromethane at room

temperature for 2-16 h;

or treating the compound of fo

with the compound of formula 8 (ii):

A-NH₂

8 (ii)

wherein A is as defined above;

in presence of carbonyl diimidazole as the coupling agnet in THF as the solvent at room temperature for about 24 h; and

Step b) hydrolysis of compounds of formula 1 a;

wherein Z is:

R₃ is (Ci-Ci₂)-alkyl;

by reaction with aqueous LiOH in a solvent selected from THF or methanol or a mixture thereof, at room temperature for 2-16 h into the corresponding carboxylic acids; and conversion of the carboxylic acids obtained into their corresponding pharmaceutically acceptable salts.

37. A process for the preparation of the compound of formula 1 represented by the compound of formula 1 b:

Formula 1 b

wherein A, B and Z are as defined in claim 1 for formula 1

the steps comprising:

Step a) treating the compound of formula D:

wherein B and Z are as defined above;

with a compound of formula 8 (iii):

A-N=C=S

8 (iii)

wherein A is as defined above;

in a solvent selected from THF or dichloromethane at room temperature for 2-16 h; and

Step b) hydrolysis of compounds of formula 1 b;

wherein Z is:

R₃ is (Ci-Ci₂)-alkyl;

by reaction with aqueous LiOH in a solvent selected from THF or methanol or a mixture thereof, at room temperature for 2-16 h into the corresponding carboxylic acids of formula 1 b (R₃ is H); and conversion of the carboxylic acids obtained into their corresponding pharmaceutically acceptable salts.

38. A process for the preparation of the compound of formula 1 represented by the compound of formula 1 c:

Formula 1 c

wherein A, B and Z are as defined in claim 1 for formula 1

the steps comprising:

Step a) treating the compound of formula D:

wherein B and Z are as defined above;

with a compound of formula 8 (iv):

A-C(0)-Cl

8 (iv)

wherein A is as defined above;

in a solvent selected from dichloromethane or chloroform in pyridine as the base at room temperature for 1 -2 h;

or by reacting compound of formula D:

with a compound of formula 8 (v):

8(v)

wherein A and R₃ are as defined above; in toluene as the solvent and

trimethylaluminium as the coupling agent ; and

Step b) hydrolysis of compounds of formula 1 c; wherein Z is:

R₃ is (Ci-Ci₂)-alkyl;

by reaction with aqueous LiOH in a solvent selected from THF or methanol or a mixture thereof, at room temperature for 2-16 h into the corresponding carboxylic acids of formula 1 c (R₃ is H); and conversion of the carboxylic acids obtained into their corresponding pharmaceutically acceptable salts.

39. A process for the preparation of the compound of formula 1 represented by the compound of formula 1 d:

Formula 1 d

wherein A, B and Z are as defined in claim 1 for formula 1

the steps comprising:

Step a) treating the compound of formula D:

wherein B and Z are as defined in claim 1 for formula 1 ;

with compound of formula 8 (vi):

A-S0₂-Cl

8 (vi)

wherein A is as defined above;

in a solvent selected from dichloromethane or chloroform in pyridine as the base at room temperature for 1 -2 h; and

Step b) hydrolysis of compounds of formula 1 d;

wherein Z is:

R₃ is (Ci-Ci₂)-alkyl;

by reaction with aqueous LiOH in a solvent selected from THF or methanol or a mixture thereof, at room temperature for 2-16 h into the corresponding carboxylic acids of formula 1 d (R₃ is H); and conversion of the carboxylic acids obtained into their corresponding pharmaceutically acceptable salts.

40. A process for the preparation of compound of formula 1 e:

Formula 1 e

wherein A, B, Z and R₆ are as defined in claim 1 for formula 1 ;

the steps comprising:

Step a) reacting the compound of formula 1 b:

Formula 1 b

with the compound of formula 8 (vii):

R₆-NH₂

8 (vii)

wherein R₆ is as defined in claim 1 for formula 1 ;

in presence of HgO in methanol as the solvent at room temperature for 1 -3 h; and Step b) hydrolysis of compounds of formula 1 e;

wherein Z is:

R₃ is (Ci-Ci₂)-alkyl;

by reaction with aqueous LiOH in a solvent selected from THF or methanol or a mixture thereof, at room temperature for 2-16 h into the corresponding carboxylic acids of formula 1 e (R₃ is H); and conversion of the carboxylic acids obtained into their corresponding pharmaceutically acceptable salts.

41 . A process for the preparation of compound of formula D as defined in claim 35 represented by the following formula 8:

wherein R₃ is (CrCi₂)-alkyl; R_{1 5} R₂ and n are as defined in claim 1 for formula 1 ;

the steps comprising:

Step a) preparation of compound of formula 3:

in presence of anhydrous AICI₃ as the catalyst in dry ether at a temperature range of 0 °C to 35 °C for 4-8 h;

Step b) reacting the compound of formula 3 with hexamethylene tetramine in a solvent selected from dichloromethane or chloroform at room temperature for 4-16 h, to yield the corresponding hexamine salt, which may be hydrolysed by HCI in a solvent selected from ethanol or methanol to yield compound of formula 4;

Step c) preparing a compound of formula 5: wherein W is OH; R₃ is (CrCi₂)-alkyl; R_{1 ;} R₂ and n are as defined in claim 1 of formula 1 ;

by the partial hydrolysis of the corresponding diester by using methanolic KOH or by treatment of the corresponding anhydride with concentrated H₂S0₄ in methanol;

Step d) reacting compound of formula 5 with isobutylchloroformate in presence of N- methylmorpholine as the base in a solvent selected from THF or DMF at a temperature range of -20 °C to -30 °C to form a carbonate, which is further reacted with the compound of formula 4 in presence of triethylamine as the base in a solvent selected from THF or DMF at room temperature, to yield compound of formula 6;

Step e) refluxing the compound of formula 6 with Lawesson's reagent in a solvent selected from 1 ,4-dioxane or THF, at a temperature range of 60 °C to 1 10 °C, to yield the compound of formula 7; and

Step f) reducing the compound of formula 7 with Fe and NH₄CI as the reducing agent in a solvent mixture of EtOH, THF and water at a temperature range of 70 °C to 80 °C for 2-6 h to yield compound of formula 8. 42. A process for the preparation of compound of formula D as defined in claim 35 represented by the followin formula 18:

wherein R₃ is (CrCi₂)-alkyl; R_{1 5} R₂ and n are as defined in claim 1 of formula 1 ;

the steps comprising:

Step a) preparation of com ound of formula 17:

by refluxing compound of formula 6:

with POC , optionally in presence of acetonitrile as the solvent , at a temperature range of 80 °C to 1 10 °C for 2-3 h; and

Step b) reducing the compound of formula 17 with Fe and NH₄CI as the reducing agent in a solvent mixture of EtOH, THF and water at a temperature range of 70 °C to 80 °C for 2-6 h to yield compound of formula 18.

43. A process for the preparation of compound of formula D as defined in claim 35 represented by following formula 29:

wherein R₃ is (CrCi₂)-alkyl; R_{1 5} R₂, R₄ and n are as defined in claim 1 for formula 1 ; the steps comprising:

Step a) preparation of a compound of formula 27:

by reacting a compound of formul with a compound of formula 5:

wherein W is OH; R₃ is (CrCi₂)-alkyl; R_{1 ;} R₂ and n are as defined in claim 1 of formula 1 ;

in a solvent selected from toluene, ethanol or THF at a temperature range of 60 °C to 120 °C, optionally in the presence of a base selected from sodium hydride, potassium carbonate or cesium carbonate;

Step b) refluxing compound of formula 27 with a compound of formula 27 (i);

Η,Ν-Ν

27 (i) wherein R₄ is as defined in formula 1 ; in a solvent selected from ethanol or methanol at a temperature of 60 °C to 85 °C to yield the compound of formula 28; and

Step c) reducing compound of formula 28 with Fe and NH₄CI as the reducing agent in a solvent mixture of EtOH, THF and water at a temperature range of 70 °C to 80 °C for 2- 6 h to yield compound of formula 29.

44 . A process for the preparation of compound of formula D as defined in claim 35 represented by of the following formula 43:

wherein R₃ is (CrCi₂)-alkyl; R_{1 ;} R₂ and n are as defined in claim 1 for formula 1 ;

the steps comprising:

Step a) treating a compound of formula 39:

wherein R₃ is (CrCi₂)-alkyl; R_{1 ;} R₂ and n are as defined in claim 1 of formula 1 ;

with ferf-butyl carbazate followed by reaction with sodium triacetoxy borohydride or borane-THF complex at a temperature range of 0 °C to 35 °C for about 7 h, to yield the compound of formula 40;

Step b) reacting the compound of formula 40 with 4N HCI in dioxane at a temperature range of 25 °C to 50 °C for about 10 h, to yield the compound of formula 41 ;

Step c) reacting compound of formula 38:

with the compound of formula 41 in a solvent selected from EtOH or methanol at a temperature range of 50- °C to yield the compound of formula 42; and

Step d) reducing the compound of formula 42 with Fe and NH₄CI as the reducing agent in a solvent mixture of EtOH, THF and water at a temperature range of 70 °C to 80 °C for 2-6 h to yield compound of formula 43.

45. A process for the preparation of compound of formula D as defined in claim 35 represented by of the following formula 56:

wherein R₃ is (CrCi₂)-alkyl; R_{1 ;} R₂ and n are as defined in claim 1 for formula 1 ;

the steps comprising:

Step a) reacting a compound of formula 53: with a compound of formula 5:

wherein W is OH; R₃ is (CrCi₂)-alkyl; R_{1 ;} R₂ and n are as defined in claim 1 for formula 1 ;

in dichoromethane as the solvent in presence of triethylamine as the base at room temperature for 10 to 18 h, to yield the compound of formula 54;

Step b) refluxing compound of formula 54 with POCI₃, optionally in the presence acetonitrile as the solvent , at a temperature range of 80 °C to 1 10 °C for 2-3 h, to obtain the compound of formula 55; and

Step c) reducing compound of formula 55 with Fe and NH₄CI as the reducing agent in a solvent mixture of EtOH, THF and water at a temperature range of 70 °C to 80 °C for 2-6 h to yield compound of formula 56.

46. A process for the preparation of compound of formula D as defined in claim 35 represented by the following formula 66:

wherein R₃ is (CrCi₂)-alkyl; R_{1 ;} R₂ and n are as defined in claim 1 for formula 1 ;

the steps comprising:

Step a) refluxing the compound of formula 54:

with Lawesson's reagent in a solvent selected from 1 ,4-dioxane or THF, at a temperature range of 80 °C to 1 10 °C, to yield the compound of formula 65; and

Step b) reducing compound of formula 65 with Fe and NH₄CI as the reducing agent in a solvent mixture of EtOH, THF and water at a temperature range of 70 °C to 80 °C for 2- 6 h to yield compound of formula 66.

47. A process for the preparation of compound of formula D as defined in claim 35 represented by of the following formula 78:

wherein R₃ is (Ci-Ci₂)-alkyl; Ri, R₂ and n are as defined in claim 1 for formula 1 ;

the steps comprising:

Step a) reacting compound of formula 75:

75 with hydroxylamine hydrochloride in presence of K₂C0₃ as the base in a solvent selected from MeOH or EtOH at a temperature range of 50 °C to 80 °C for 4-10 h, to yield the compound of formula

Step b) reacting compound of formula 76 with compound of formula 5

wherein W is OH; R₃ is (CrCi₂)-alkyl; R_{1 ;} R₂ and n are as defined in claim 1 for formula 1 ;

in a solvent selected from dichloromethane or chloroform in presence of carbonylimidazole as the coupling reagent at room temperature for 8-10 h, followed by cyclisation by refluxing in toluene at a temperature range of 100 °C to 130 °C for about 18 h, to yield the compou

Step c) reducing compound of formula 77 with Fe and NH₄CI as the reducing agent in a solvent mixture of EtOH, THF and water at a temperature range of 70 °C to 80 °C for 2-6 h to yield compound of formula 78. 48. A process for the preparation of compound of formula D as defined in claim 35 represented by of the following formula 90:

wherein R₃ is (CrCi₂)-alkyl; R_{1 ;} R₂ and m are as defined in claim 1 for formula 1 ;

the steps comprising:

Step a) preparation of compound of formula 87:

wherein W is OH; R₃ is (CrCi₂)-alkyl; R_{1 ;} R₂ and m are as defined in claim 1 for formula 1 ;

the steps comprising:

(i) reacting compound of formula A:

with ferf-butyl-2-(diethoxy phosphoryl)acetate in presence of sodium hydride as the base in THF as the solvent at 0 °C for about 1 h, followed by at room temperature for about 16 h, to yield the com ound of formula B;

(ii) hydrogenation of compound of formula B in presence of Pd/C as the catalyst in a solvent selected from ethyl acetate, ethanol or methanol at room temperature, to yield the compound of formula C;

(iii) partial hydrolysis of the compound of formula C in the presence of KOH as the base in a solvent mixture of methanol and water at room temperature for about 2 h to yield the compound of formula 87 wherein m=1 ;

Step b) reaction of compound of formula 4:

with compound of formula 87 in presence of BOP (benzotriazol-1 - yloxy)tris(dimethylamino)phosphonium hexafluorophosphate) as the coupling agent and triethylamine as the base in a solvent selected from DMF or THF at a temperature range of 50 °C to 6 °C, to yield the compound of formula 88;

Step c) refluxing compound of formula 88 with Lawesson's reagent in a solvent selected from 1 ,4-dioxane or THF, at a temperature range of 80 °C to 1 10 °C, to yield the compound of for

Step d) reducing the compound of formula 89 with Fe and NH₄CI as the reducing agent in a solvent mixture of EtOH, THF and water at a temperature range of 70 °C to 80 °C for 2-6 h to yield compound of formula 90.

49. A process for the preparation of compound of formula D as defined in claim 35 represented by of the following formula 100:

wherein R₃ is (CrCi₂)-alkyl; R_{1 ;} R₂ and m are as defined in claim 1 for formula 1 ;

the steps comprising:

Step a) refluxing compound of formula 88 ;

with POCI₃, optionally in presence of acetonitrile as the solvent , at a temperature range of 80 °C to 1 10 °C for 2-3 h, to yield the compound of formula 99; and

Step b) reducing the compound of formula 99 with Fe and NH₄CI as the reducing agent in a solvent mixture of EtOH, THF and water at a temperature range of 70 °C to 80 °C for 2-6 h to yield compound of formula 100.

50. A process for the preparation of compound of formula D as defined in claim 35 represented by of the following formula 110:

wherein R₃ is (CrCi₂)-alkyl; R_{1 ;} R₂, R₄ and m are as defined in claim 1 for formula 1 ; the steps comprising: Step a) reacting compound of formula 2:

with compound of formula 87:

wherein W is OH; R₃ is (CrCi₂)-alkyl; R_{1 ;} R₂ and m are as defined in claim 1 for formula 1 ;

in a solvent selected from toluene, ethanol or THF at a temperature range of 60 °C to 120 °C, optionally in presence of a base selected from sodium hydride, potassium carbonate or cesium carbonate, to yield the compound of formula 87(i);

87(i)

which may be refluxed with compound 27 (i); wherein R₄ is as defined in formula 1 ; in a solvent selected from ethanol or methanol at a temperature of 60 °C to 85 °C, to yield the compound of formula 109; and

Step b) reducing the compound of formula 109 with Fe and NH₄CI as the reducing agent in a solvent mixture of EtOH, THF and water at a temperature range of 70 °C to 80 °C for 2-6 h to yield compound of formula 110. 51 . A process for the preparation of compound of formula D as defined in claim 35 represented by of the followin formula 123:

wherein R₃ is (CrCi₂)-alkyl; R_{1 ;} R₂ and m are as defined in claim 1 for formula 1 ;

the steps comprising:

Step a) reacting compound of formula 119:

wherein R₃ is (CrCi₂)-alkyl; R_{1 ;} R₂ and m are as defined in claim 1 for formula 1 ;

with ferf-butyl carbazate followed by reaction with sodium triacetoxy borohydride or borane-THF complex at a temperature range of 0 °C to 35 °C for about 7 h, to yield the compound of formula 120;

Step b) reacting compound of formula 120 with 4N HCI in dioxane at a temperature range of 25 °C to 50 °C for about 10 h, to yield the compound of formula 121 ;

Step c) reacting compound of formula 38:

with the compound of formula 121 in a solvent selected from EtOH or methanol at a temperature range of 50 °C to 80 °C to yield the compound of formula 122; and

Step d) reducing compound of formula 122 with Fe and NH₄CI as the reducing agent in a solvent mixture of EtOH, THF and water at a temperature range of 70 °C to 80 °C for 2-6 h to yield compound of formula 123.

52. A process for the preparation of compound of formula D as defined in claim 35 represented by of t

wherein R₃ is (CrCi₂)-alkyl; R_{1 ;} R₂ and m are as defined in claim 1 for formula 1 ;

the steps comprising:

Step a) reaction of compound of formula 53:

wherein W is OH; R₃ is (CrCi₂)-alkyl; R_{1 ;} R₂ and m are as defined in claim 1 for formula 1 ;

in dichloromethane as the solvent in the presence of triethylamine as the base at room temperature for 10-18 h, to yield the compound of formula 132;

Step b) refluxing compound of formula 132 with POCI₃, optionally in the presence of acetonitrile as the solvent, at a temperature range of 80 °C to 1 10 °C for 2-3 h, to obtain the compou

Step c) reducing compound of formula 133 with Fe and NH₄CI as the reducing agent in a solvent mixture of EtOH, THF and water at a temperature range of 70 °C to 80 °C for 2-6 h to yield compound of formula 134.

53. A process for the preparation of compound of formula D as defined in claim 35 represented by of the following formula 145:

wherein R₃ is (CrCi₂)-alkyl; R_{1 ;} R₂ and m are as defined in claim 1 for formula 1 ;

the steps comprising:

Step a) reacting compound of formula 53:

with compound of formula 87

wherein W is OH; R₃ is (CrCi₂)-alkyl; R_{1 ;} R₂ and m are as defined in claim 1 for formula 1 ;

in dichloromethane as the solvent in presence of triethylamine as the base at room temperature for 10-18 h, to yield the compound of formula 143;

Step b) refluxing compound of formula 143 with Lawesson's reagent in a solvent selected from 1 ,4-dioxane or THF, at a temperature range of 80 °C to 1 10 °C, to yield the compound of f

Step c) reducing compound of formula 144 with Fe and NH₄CI as the reducing agent in a solvent mixture of EtOH, THF and water at a temperature range of 70 °C to 80 °C for 2-6 h to yield compound of formula 145.

54. A process for the preparation of compound of formula D as defined in claim 35 represented by of the following formula 155:

wherein R₃ is (CrCi₂)-alkyl; R_{1 ;} R₂ and m are as defined in claim 1 for formula 1 ;

the steps comprising:

Step a) reacting compound of formula 76:

with compound of formula 87:

wherein W is OH; R₃ is (CrCi₂)-alkyl; R_{1 ;} R₂ and m are as defined in claim 1 for formula 1 ;

in a solvent selected from dichloromethane or chloroform in presence of carbonylimidazole as the coupling agent at room temperature for 8-10 h, followed by cyclisation by refluxing in toluene at a temperature range of 100 °C to 130 °C for about 18 h, to yield the c

Step b) reducing compound of formula 154 with Fe and NH₄CI as the reducing agent in a solvent mixture of EtOH, THF and water at a temperature range of 70 °C to 80 °C for 2-6 h to yield compound of formula 155.

55. A process for the preparation of compound of formula D as defined in claim 35 represented by of the following formula 166:

wherein R_{1 5} R₂ and m are as defined in claim 1 for formula 1 ;

the steps comprising:

Step a) reacting compound of formula 89:

89 (R₃ is ethyl)

with hydrazine hydrate in ethanol as the solvent at 80 °C for 4-6 h to yield the compound of formula 164;

Step b) reacting compound of formula 164 with acetic acid and POCI₃ at 80 °C for 2-4 h to yield the compound of fo

Step c) reducing compound of formula 165 with Fe and NH₄CI as the reducing agent in a solvent mixture of EtOH, THF and water at a temperature range of 70 °C to 80 °C for 2-6 h to yield compound of formula 166.

56. A process for the preparation of compound of formula D as defined in claim 35 represented by the following formula 171 : wherein R_{1 5} R₂ and m are as defined in claim 1 for formula 1 ;

the steps comprising:

Step a) hydrolyzing compound of formula 89 (R₃=ethyl):

89 (R₃ is ethyl)

by reacting with NaOH in a solvent mixture of THF and methanol at room temperature for 16 h to yield compound of formula 89 (R₃=H):

89 (R₃ = H)

Step b) reacting the compound of formula 89 (R₃=H) with oxalyl chloride and N- hydroxyacetamidine in a solvent selected from DCE or dioxane at room temperature for 32 h to yield compound

Step c) heating the compound of formula 169 in DMF in a microwave at 120 °C for 2-4 h to yield compound of form

Step d) reducing compound of formula 170 with Fe and NH₄CI as the reducing agent in a solvent mixture of EtOH, THF and water at a temperature range of 70 °C to 80 °C for 2-6 h to yield compound of formula 171.

57. A process for the preparation of compound of formula D as defined in claim 35 represented by of the following formula 172:

wherein R_h R₂ and m are as defined in claim 1 for formula 1 ;

by reducing the compound of formula 170:

with sodium sulphide as the reducing agent in a solvent mixture of dioxane and water at a temperature range of 70 °C to 90 °C for 1 h. 58. A process for the preparation of compound of formula D as defined in claim 35 represented by of the following formula 179:

wherein R_{1 ;} R₂ and m are as defined in claim 1 for formula 1 ;

the steps comprising:

Step a) reacting compound of formula 89:

89 (R₃ is ethyl)

with oxalyl chloride and acetic hydrazide in a solvent selected from DCE or dioxane at room temperature for 32 h to yield compound of formula 177;

Step b) reacting the compound of formula 177 with Lawesson's reagent in a solvent selected from 1 ,4-dioxane or xylene at a temperature range of 100 °C to 150 °C, to yield compound of formula

Step c) reducing the compound of formula 178 with Fe and NH₄CI as the reducing agent in a solvent mixture of EtOH, THF and water at a temperature range of 70 °C to 80 °C for 2-6 h to yield compound of formula 179.

59. A process for the preparation of compound of formula D as defined in claim 35 represented by of the following formula 192:

wherein R_{1 5} R₂, R5 and n are as defined in claim 1 for formula 1 ;

the steps comprising:

Step a) reacting compound of formula 186:

186

wherein R_{1 5} R₂ and n are as defined above;

with BOC-anhydride in presence of NaHC0₃ as the base in a solvent mixture of acetonitrile and water at a temperature range of 0 ^°C to room temperature for 16 h to yield compound of formula 187;

187

Step b) reacting the compound of formula 187 with 2-amino-1 -(4-nitrophenyl)ethanone hydrochloride in presence of a mixture of HATU and triethylamine as the base in DMF as the solvent at room temp und of formula 188;

188

Step c) reacting the compound of formula 188 with Lawesson's reagent by refluxing in a solvent selected from 1 ,4-dioxane or THF, at a temperature range of 60 °C to 1 10 °C for 1 -3 h, to yield the compound of formula 189;

Step d) reacting the compound of formula 189 with HCI in 1 ,4-dioxane at room temperature for 20 h to yield the compound of formula 190;

Step e) reacting the compound of formula 190 with the reagent:

wherein R₅ is as defined in claim 1 for formula 1 ;

in presence of triethylamine as the base in dichloromethane at room temperature for 1 - 3 h to yield compound of formul

Step f) reducing the compound of formula 191 with Fe and NH₄CI as the reducing agent in a solvent mixture of EtOH, THF and water at a temperature range of 70 °C to 80 °C for 2-6 h to yield compound of formula 192.

60. A process for the preparation of compound of formula D as defined in claim 35 represented by of the following formula 215:

wherein R_{1 5} R₂, R5 and m are as defined in claim 1 for formula 1 ;

the steps comprising:

Step a) hydrolyzing compound yl):

using 1 N NaOH in a solvent mixture of THF and methanol at room temperature for 16- 24 h to yield compound of formu

7 (R₃ is H)

Step b) refluxing the compound of formula 7 (R₃ is H) with the reagent:

wherein R₅ is defined in claim 1 for formula 1 ;

in presence of isobutyl chloroformate in presence of a base selected from N-Methyl morpholine and DBU in THF for 16 h to yield compound of formula 205;

205

Step c) reducing the compound of formula 205 with Fe and NH₄CI as the reducing agent in a solvent mixture of EtOH, THF and water at a temperature range of 70 °C to 80 °C for 2-6 h to yield compound of formula 206.

61 . A process for the preparation of compound of formula D as defined in claim 35 represented by the following formula 215:

wherein R_{1 5} R₂, R5 and m are as defined in claim 1 for formula 1 ;

the steps comprising:

Step a) reacting a compound of formula 210:

wherein R_{1 ;} R₂ and n are as defined in claim 1 for formula 1 ;

is reacted with triflic anhydride in presence of DIPEA as the base in dichloromethane as the solvent at room temperature for 16 h to yield compound of formula 211 ;

Step b) hydrolyzing the compound of formula 211 using LiOH in as THF at room temperature for 16 h to yield the compound of formula 212;

212

Step c) reacting the compound of formula 212 with 2-amino-(4-nitro)acetophenone hydrochloride in the presence of HATU as the coupling agnet and triethyl amine as the base in DMF as the solvent at room temperature for 3-5 h to yield the compound of formula 213;

Step d) refluxing the compound of formula 213 with Lawesson's reagent in a solvent selected from 1 ,4-dioxane or THF, at a temperature range of 60 °C to 1 10 °C, to yield the compound of formula

Step c) reducing compound of formula 214 with Fe and NH₄CI as the reducing agent in a solvent mixture of EtOH, THF and water at a temperature range of 70 °C to 80 °C for 2-6 h to yield compound of formula 215.

62. A process for the preparation of compound of formula D as defined in claim 35 represented by of the f

wherein R_{1 5} R₂ and m are as defined in claim 1 for formula 1 ;

the steps comprising:

Step a) refluxing a compound of formula 3:

with the compound of formula 21

at a temperature range of 75 °C to 85 °C for 3-5 h to yield the compound of formula 220;

Step b) reacting the compound of formula 220 with 1 N HCI in ethyl acetate as the solvent at room temperature to yield the compound of formula 221 ;

Step c) reacting the compound of formula 221 with the reagent

wherein X is halogen; m, R_{1 5} R₂ and R₃ are as defined in claim 1 for formula 1 ;

in presence of a base such as triethylamine in toluene at a temperature range of 100

°C to 120 °C to yield the compound of formula 222; and

Step d) reducing the compound of formula 222 with Fe and NH₄CI as the reducing agent in a solvent mixture of EtOH, THF and water at a temperature range of 70 °C to 80 °C for 2-6 h, to yield compound of formula 223.

63. A process for the preparation of compound of formula D as defined in claim 35 represented by the following formula 229:

the steps comprising:

Step a) reacting compound of formula 4:

with a compound of formula 22

in presence of DIPEA as the base in DMF as the solvent in presence of HATU as the coupling agent at room temperature for 30 min to 1 h to yield the compound of formula 227;

Step b) reacting the compound of formula 227 is reacted with Lawesson's reagent in dioxane at 50 °C to 70 °C for 2-4 h to yield the compound of formula 228; and

Step c) reducing the compound of formula 228 with Fe and NH₄CI as the reducing agent in a solvent mixture of EtOH, THF and water at a temperature range of 70 °C to 80 °C for 2-6 h, to yield compound of formula 229.

64. A process for the preparation of compound of formula D as defined in claim 35 represented by of the following formula 234:

wherein R_{1 5} R₂, R3 and m are as defined in claim 1 for formula 1 ;

the steps comprising:

Step a) reacting compound of formula 228:

with 1 N HCI in ethyl acetate as the solvent at room temperature to yield the compound of formula 232;

Step b) reacting the compound of formula 232 is reacted with the reagent:

wherein X is halogen; m, R_{1 ;} R₂ and R₃ are as defined in claim 1 for formula 1 ;

in presence of triethylamine as the base in toluene at a temperature range of 100 °C to

120 °C to yield the compound of formula 233; and

Step c) reducing the compound of formula 233 with Fe and NH₄CI as the reducing agent in a solvent mixture of EtOH, THF and water at a temperature range of 70 °C to 80 °C for 2-6 h, to yield compound of formula 234.

65. A process for the preparation of compound of formula D as defined in claim 35 represented by compound of formula 240:

Step a) reacting compound of formula 232 :

with t-butyl 2-bromoethylcarbamate in the presence of K₂C0₃ as the base in DMF as the solvent at a temperature range of 50 °C to 80 °C for 2-4 h to yield the compound of formula 237;

Step b) reacting the compound of formula 237 with HCI in a solvent selected from isopropanol or methanol at room temperature for 12-15 h to yield the compound of formula 238;

Step c) reacting the compound of formula 238 with triflic anhydride in dichloromethane as the solvent and triethylamine as the base at room temperature for 10-16 h to yield the compound of form

Step d) reducing the compound of formula 239 with Fe and NH₄CI as the reducing agent in a solvent mixture of EtOH, THF and water at a temperature range of 70 °C to 80 °C for 2-6 h, to yield compound of formula 240.

66. A process for the preparation of compound of formula D as defined in claim 35 represented by of the following formula 243:

Step a) reacting compound of formula 232:

with a reagent:

wherein R₅ is as defined in formula 1 ; in the presence of triethylamine as the base in dichloromethane as the solvent at room temperature for 16 h to yield the compound of formula 242; and

Step b) reducing the compound of formula 242 with Fe and NH₄CI as the reducing agent in a solvent mixture of EtOH, THF and water at a temperature range of 70 °C to 80 °C for 2-6 h, to yield compound of formula 243.

67. A process for the preparation of compound of formula D as defined in claim 35 represented by of the following formula 249:

the steps comprising:

Step a) reacting the compound of formula 245:

with KOH as the base in methanol at a temperature range of 60 °C to 80 °C for 16 h followed by acidification with dilute HCI to yield the compound of formula 246;

Step b) reacting the compound of formula 246 with the compound of formula 4 in presence of HATU as the coupling agent and DIPEA as the base in DMF at room temperature for 30 min t 247;

Step c) reacting the compound of formula 247 with Lawesson's reagent dioxane as the solvent at 50 °C to 70 °C ula 248; and

Step d) reducing the compound of formula 248 with Fe and NH₄CI as the reducing agent in a solvent mixture of EtOH, THF and water at a temperature range of 70 °C to 80 °C for 2-6 h, to yield compound of formula 249.

Description:

HETEROCYCLIC COMPOUNDS AS DGAT1 INHIBITORS

FIELD OF THE INVENTION

The present invention relates to heterocyclic compounds, to processes for their preparation, pharmaceutical compositions containing them, and their use in the prevention and treatment of diseases or disorders mediated by diacylglycerol acyltransf erase (DGAT), particularly DGAT1 .

BACKGROUND OF THE INVENTION

Obesity is a disease of energy imbalance, when energy input is more than output. Excess energy is stored in the form of triglycerides (TGs) in the adipose tissue. Increased adipose cell size causes hypertrophic obesity and increased cell number causes hyperplastic obesity characteristic of a more severe condition. The key causes of obesity are the increased consumption of energy-rich but nutrient-poor diets (like saturated fats and sugars) and reduced physical activity. 65 % of the US population is overweight, where body mass index (BMI) is greater than 25 and approximately 25 % of them are obese, having BMI > 30. The prevalence of obesity has increased dramatically over the last decade. Obesity leads to increased risk of chronic diseases such as type 2 diabetes, insulin resistance, hypertension, stroke, cardiovascular diseases, respiratory problems, gall bladder disease, osteoarthritis, sleep apnea and certain cancers (Expert Opin. Ther. Targets, 2009, 13, 2, 195-207). The increasing evidence that severe obesity has a genetic basis, resulting in maintaining and defending an elevated weight, may explain why long-term weight loss is very difficult to achieve. This has strengthened the argument that severe obesity should be treated with pharmacological agents along with conventional diet and exercise regimes.

Diacylglycerol acyltransferase (DGAT) is an enzyme that catalyses the biosynthesis of triglyceride at the final step of the process, converting diacylglycerol (DAG) and fatty acyl-coenzyme A (CoA) into triglyceride. The enzymatic activity is present in all cell types because of the necessity of producing triglyceride for cellular needs. The amount of triglyceride synthesized varies from cell to cell, with the adipocytes, hepatocytes and intestinal enterocytes producing much more triglyceride, for storage or incorporation into lipoproteins, than other cell types. Because of its critical role in the biosynthesis of triglyceride, a neutral lipid that is the densest form of energy storage in animals, alteration of the expression and/or activity of DGAT in any of the tissues or organs would be expected to perturb the systemic energy metabolism. Diacyl glycerolacyltransferase 1 (DGAT1 ) is one of two known DGAT enzymes that catalyze the final step in triglyceride synthesis. Although most tissues generate triacylglycerols, DGAT1 is known to be highly expressed in the intestine and adipose with lower levels in the liver and muscle. Inhibition of DGAT1 in each of these tissues (intestine, adipose, liver and muscle) would inhibit triacylglycerol synthesis and may reverse the pathophysiology of excessive lipid accumulation in human metabolic disease.

Inhibitors of varying structural types of DGAT1 have been reported to be potential agents for the treatment for obesity and other disorders. The particular interest in DGAT1 inhibition stems from the reported phenotype of DGAT1 deficient (Dgatl -/-) mice. These animals are viable, resistant to weight gain when fed a high-fat diet, and show increased insulin and leptin sensitivity (Nature Genetics, 2000, 25, 87-90). Resistance to weight gain results from increased energy expenditure rather than decreased food intake (the animals are in fact hyperphagic) and is associated with loss of adipose rather than lean tissue mass. Most aspects of this phenotype can be reproduced in rodents by treatment with a potent and selective small molecule inhibitor of DGATL DGAT1 inhibitors may also have utility for the treatment of skin disorders such as acne (The Journal of Biological Chemistry, 2009, 284, 7, 4292-4299).

XP620 (BMS) has been reported to be a selective DGAT1 inhibitor, which is able to block DGAT1 mediated retinyl-ester formation in Caco-2 cells. The potency against DGAT1 was in the order of 100 nM with no activity against DGAT2.

Other small-molecule inhibitors reported are aryl alkyl acids from Bayer, phosphonic acid diesters from Otsuka, substituted ureas from Sankyo, pyrrolo [1 ,2-b]pyridazine derivatives from Tularik (now Amgen) and oxadiazoles from AstraZeneca (Expert Opin. Ther. Targets, 2006, 10, 5, 749-757).

The PCT publication, WO2007016538 discloses biphenyl amino acid derivatives, and pharmaceutical salts and esters thereof, that have utility in the inhibition of DGAT1 and in the treatment of obesity and related diseases.

The Japanese patent publication, JP2008255024 discloses biarylamine derivatives for the inhibition of DGATL

US Patent 7625914 discloses substituted propanoic acid derivatives as modulators of PPAR-γ type receptors, useful for treating conditions or disorders such as cardiovascular diseases, immune diseases and/or diseases associated with lipid metabolism. Despite the recent advances in this field, there still exists a need for effective and safe pharmacotherapy for obesity.

SUMMARY OF THE INVENTION

The present invention relates to heterocyclic compounds, processes for their preparation and their use in the prevention and treatment of diseases or disorders mediated by diacylglycerol acyltransferase (DGAT), particularly DGAT1 .

According to one aspect of the present invention, there are provided heterocyclic compounds of formula 1 (as described herein below), as well as stereoisomers, tautomeric forms, pharmaceutically acceptable salts, solvates, polymorphs, prodrugs, carboxylic acid isosteres and N-oxides thereof.

According to another aspect of the present invention, there are provided processes for producing the heterocyclic compounds of formula 1 .

According to a further aspect, there is provided the use of heterocyclic compounds of formula 1 in the prevention or treatment of diseases or disorders mediated by diacylglycerol acyltransferase (DGAT), particularly DGAT1 .

According to another aspect of the present invention, there are provided pharmaceutical compositions including heterocyclic compounds of formula 1 as active ingredient.

According to yet another aspect of the present invention, there is provided a method for the prevention or treatment of diseases or disorders mediated by diacylglycerol acyltransferase (DGAT), particularly DGAT1 , the method including administering to a mammal in need thereof a therapeutically effective amount of a compound of formula 1 .

According to a further aspect of the present invention, there is provided use of compounds of formula 1 for the manufacture of medicaments, which are useful for the prevention or treatment of diseases or disorders mediated by diacylglycerol acyltransferase (DGAT), particularly DGAT1 . DETAILED DESCRIPTION OF THE INVENTION

The present invention provides compounds of formula 1 :

Formula 1

in all their stereoisomeric and tautomeric forms; and their pharmaceutically acceptable salts, solvates, polymorphs, prodrugs, carboxylic acid isosteres and N-oxides;

wherein,

Z is selected from:

indicates the point of attachment;

n is an integer selected from 1 -5;

m is 0 or 1 ;

Ri and R ₂ are independently selected from hydrogen or (CrCi ₂)-alkyl, or R- _\ and R ₂ can optionally form an unsubstituted or substituted (C ₃-C ₇) cycloalkyl ring;

R ₃ is hydrogen or (CrCi ₂)-alkyl;

R ₅ is selected from hydrogen, (CrCi ₂)-alkyl, CF ₃, (C ₃-C ₇)-cycloalkyl, aryl or heterocyclyl; B is a 5-membered heteroaryl ring represented by any one of the general structures (i) to (x);

wherein 1 and 2 are the points of attachment of B to phenyl and to Z respectively and R ₄ is selected from hydrogen, (CrCi ₂)-alkyl or aryl; or B is a 6-membered heteroaryl ring containing 1 or 2 N-atoms, wherein the 6-membered heteroaryl ring may be unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (CrCi ₂)-alkoxy, cyano, nitro, (CrCi ₂)-alkyl, (C ₂-Ci ₂)-alkenyl, (C ₂-Ci ₂)-alkynyl, (C ₃-Ci ₂)- cycloalkyl, aryl, aryloxy, heterocyclyl or O-heterocyclyl;

L is selected from ^*NHC(0)NH, ^*N(CH ₃)C(0)NH ^*NHC(S)NH, ^*S0 ₂NH, ^*CONH or ^*NH(C=NR ₆)NH, wherein ^* indicates the point of attachment of L to A, and R ₆ is selected from hydrogen, methyl, cyano or nitro;

A is selected from (Ci-Ci ₂)-alkyl, (C ₃-Ci ₂)-cycloalkyl, aryl or heterocyclyl; wherein,

(Ci-Ci ₂)-alkyl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (Ci-Ci ₂)-alkoxy, cyano, nitro, (C ₃-Ci ₂)-cycloalkyl, aryl, heterocyclyl, C(0)Rp, C(0)OR _p, NRpRq, C(0)NR _pR _q, SR _P, S(0)R _p or S0 ₂R _p;

(C ₃-Ci ₂)-cycloalkyl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (Ci-Ci ₂)-alkoxy, cyano, nitro, aryl, heterocyclyl, C(0)R _p, C(0)OR _p, NR _pRq, C(0)NR _pR _q, SR _P, S(0)R _p or S0 ₂R _p;

aryl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (Ci-Ci ₂)-alkoxy, cyano, nitro, (CrCi ₂)-alkyl, OCF ₃, CF ₃, (C ₂-Ci ₂)-alkenyl, (C ₂- Ci ₂)-alkynyl, (C ₃-Ci ₂)-cycloalkyl, aryl, aryloxy, heterocyclyl, O-heterocyclyl, C(0)R _p, C(0)OR _p, NR _pRq, C(0)NR _pR _q, SR _P, S(0)R _p or S0 ₂R _p; or aryl may be fused with an unsubstituted or substituted 5 or 6-membered cycloalkyl ring optionally containing one or more heteroatoms selected from O, N or S; heterocyclyl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (CrCi ₂)-alkoxy, cyano, nitro, (CrCi ₂)-alkyl, (C ₂-Ci ₂)-alkenyl, (C ₂- Ci ₂)-alkynyl, (C ₃-Ci ₂)-cycloalkyl, aryl, aryloxy, heterocyclyl, O-heterocyclyl, C(0)R _p, C(0)OR _p, NRpRq, C(0)NRpR _q, SR _P, S(0)R _p or S0 ₂R _p;

R _p and R _q are independently selected from hydrogen, (CrCi ₂)-alkyl, aryl, aralkyi or heterocyclyl, or R _p and R _q together with the N to which they are attached optionally form a 3 to 7 membered ring;

with a proviso that A is not a methyl group. Definitions

As used herein, the term "alkyl" whether used alone or as part of a substituent group, refers to the radical of saturated aliphatic groups, including straight or branched- chain alkyl groups. An alkyl group can have a straight chain or branched chain containing 1 to 12 carbon atoms. Alkyl groups include methyl, ethyl, n-propyl, isopropyl, n-butyl, t-butyl, iso-butyl, sec-butyl, neo-pentyl, n-pentyl, n-heptyl, n-octyl, n-nonyl and n-decyl groups.

A substituted alkyl refers to an alkyl group substituted with one or more groups selected from halogen, hydroxy, cyano, nitro, unsubstituted or substituted (C ₁-C ₁₂)- alkoxy, unsubstituted or substituted cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted heterocyclyl, C(0)R _p, C(0)OR _P, SR _P, S(0)R _p, S0 ₂R _p, NR _pR _q or C(0)NR _pR _q; wherein R _p and R _q are independently selected from hydrogen, unsubstituted or substituted (Ci-Ci ₂) alkyl, unsubstituted or substituted aryl, unsubstituted or substituted aralkyi and unsubstituted or substituted heterocyclyl, or R _p and R _q together with the N to which they are attached optionally form a 3 to 7 membered ring. Examples of substituted alkyls include benzyl, hydroxymethyl, hydroxyethyl, 2-hydroxyethyl, N-morpholinomethyl, N-indolomethyl, piperidinylmethyl, trifluoromethyl and aminoethyl.

As used herein, the term "alkenyl" whether used alone or as part of a substituent group, refers to a straight or branched chain hydrocarbon radical containing the indicated number of carbon atoms and at least one carbon-carbon double bond (two adjacent sp ² carbon atoms). For example, (C ₂-Ci ₂)-alkenyl refers to an alkenyl group having 2 to 12 carbon atoms. Similarly, (C ₂-C ₆)-alkenyl refers to an alkenyl group having 2 to 6 carbon atoms. Depending on the placement of double bond and substituents if any, the geometry of the double bond may be entgegen (E), or zusammen (Z), cis or trans. Examples of alkenyl include, but are not limited to, vinyl, allyl and 2-propenyl.

A substituted alkenyl refers to an alkenyl group substituted with one or more groups selected from halogen, hydroxy, cyano, nitro, unsubstituted or substituted (d- Ci ₂)-alkoxy, unsubstituted or substituted aryl, unsubstituted or substituted heterocyclyl, C(0)R _p, C(0)OR _p, SR _P, S(0)R _p, S0 ₂R _P, NR _pR _q or C(0)NR _pR _q; wherein R _p and R _q are independently selected from hydrogen, unsubstituted or substituted (C ₁-C ₁₂) alkyl, unsubstituted or substituted aryl, unsubstituted or substituted aralkyl and unsubstituted or substituted heterocyclyl, or R _p and R _q together with the N to which they are attached optionally form a 3 to 7 membered ring.

As used herein, the term "alkynyl" whether used alone or as part of a substituent group, refers to a straight or branched chain hydrocarbon radical containing the indicated number of carbon atoms and at least one carbon-carbon triple bond (two adjacent sp carbon atoms). For example, (C ₂-Ci ₂)-alkynyl refers to an alkynyl group having 2-12 carbon atoms. Examples of alkynyl include, but are not limited to, ethynyl, 1 -propynyl, 3-propynyl and 3-butynyl.

A substituted alkynyl refers to an alkynyl group substituted with one or more groups selected from halogen, hydroxy, cyano, nitro, unsubstituted or substituted (d- Ci ₂)-alkoxy, unsubstituted or substituted aryl, unsubstituted or substituted heterocyclyl, C(0)R _p, C(0)OR _p, SR _P, S(0)R _p, S0 ₂R _p, NR _pR _q or C(0)NR _pR _q; wherein R _p and R _q are independently selected from hydrogen, unsubstituted or substituted (CrCi ₂) alkyl, unsubstituted or substituted aryl, unsubstituted or substituted aralkyl and unsubstituted or substituted heterocyclyl, or R _p and R _q together with the N to which they are attached optionally form a 3 to 7 membered ring.

As used herein, the term "alkoxyl" or "alkoxy" refers to a (Ci-Ci ₂)-alkyl having an oxygen radical attached thereto. Representative alkoxy groups include methoxy, ethoxy, propoxy, isopropoxy, isobutoxy and tert-butoxy.

A substituted alkoxy refers to an alkoxy group in which the alkyl is substituted with one or more groups selected from halogen, hydroxy, cyano, nitro, unsubstituted or substituted aryl, unsubstituted or substituted heterocyclyl, C(0)R _p, C(0)OR _p, SR _P, S(0)R _p, S0 ₂R _p, NR _pR _q and C(0)NR _pR _q; wherein R _p and R _q are independently selected from hydrogen, unsubstituted or substituted (Ci-Ci ₂) alkyl, unsubstituted or substituted aryl, unsubstituted or substituted aralkyl and unsubstituted or substituted heterocyclyl, or R _p and R _q together with the N to which they are attached optionally form a 3 to 7 membered ring. Examples of substituted alkoxy are trifluoromethoxy, 2-cyanoethoxy and benzyloxy group. A benzyloxy group refers to a benzyl having an oxygen radical attached thereto.

The term "(C3-C12) cycloalkyl" refers to monocyclic, bicyclic or tricyclic hydrocarbon groups of 3-12 carbon atoms, which may be optionally bridged such as adamantyl.

The term "(C ₃-C ₇) cycloalkyl" refers to monocyclic hydrocarbon groups of 3-7 carbon atoms.

A substituted (C ₃-Ci ₂) cycloalkyl refers to a "(C ₃-Ci ₂) cycloalkyl" substituted by one or more substituents such as halogen, hydroxy, unsubstituted or substituted (C Ci ₂)-alkyl, (Ci-Ci ₂)-alkoxy cyano, nitro, unsubstituted or substituted aryl, unsubstituted or substituted heterocyclyl, C(0)R _p, C(0)OR _p, SR _P, S(0)R _p, S0 ₂R _p, NR _pR _q or C(0)NR _pR _q; wherein R _p and R _q are independently selected from hydrogen, unsubstituted or substituted (Ci-Ci ₂) alkyl, unsubstituted or substituted aryl, unsubstituted or substituted aralkyl and unsubstituted or substituted heterocyclyl, or R _p and R _q together with the N to which they are attached optionally form a 3 to 7 membered ring.

The term "aryl" as used herein refers to monocyclic or polycyclic hydrocarbon groups having 6 to 14 ring carbon atoms in which the carbocyclic ring(s) present have a conjugated pi electron system. Examples of (C ₆-Ci ₄)-aryl residues are phenyl, naphthyl, fluorenyl or anthracenyl. Examples of (C ₆-Ci ₀)-aryl residues are phenyl or naphthyl. Aryl groups can be unsubstituted or substituted by one or more, for example 1 , 2, 3, 4 or 5, identical or different substituents selected from halogen, hydroxy, cyano, nitro, unsubstituted or substituted (Ci-Ci ₂) alkyl, unsubstituted or substituted (C ₂-Ci ₂)-alkenyl, unsubstituted or substituted (C ₂-Ci ₂)-alkynyl, unsubstituted or substituted (Ci-Ci ₂)- alkoxy, unsubstituted or substituted cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted aryloxy, unsubstituted or substituted heterocyclyl, O- heterocyclyl, OCF ₃, CF ₃, C(0)R _p, C(0)OR _p, SR _P, S(0)R _p, S0 ₂R _p, NR _pR _q or C(0)NR _pR _q; wherein R _p and R _q are independently selected from hydrogen, unsubstituted or substituted (C Ci ₂) alkyl, unsubstituted or substituted aryl, unsubstituted or substituted aralkyl and unsubstituted or substituted heterocyclyl, or R _p and R _q together with the N to which they are attached optionally form a 3 to 7 membered ring. In monosubstituted phenyl residues the substituent can be located in the 2-position, the 3-position or the 4- position. If the phenyl carries two substituents, they can be located in 2, 3-position, 2,4- position, 2,5-position, 2,6-position, 3,4-position or 3,5-position. Examples of monosubstituted phenyl groups are biphenyl, 4-methylphenyl, 2-trifluoromethylphenyl, 4-trifluoromethoxyphenyl, 4-cyanophenyl and 3-nitrophenyl. Examples of disubstituted phenyl groups are 3,5-difluorophenyl and 3,4-dimethoxyphenyl.

As used herein, the term "aryloxy" refers to an aryl group having an oxygen radical attached thereto. The aryl of aryloxy group as used herein may also be defined as given herein above. Representative aryloxy groups include phenyloxy, 4- chlorophenoxy, 3,4-dimethoxy phenoxy, etc.

The term "aralkyl" refers to an aryl group bonded directly through an alkyl group, such as benzyl. The aryl of the aralkyl group may be unsubstituted or substituted as explained in the definition of substituted aryl herein above.

The term "heteroatom" as used herein includes nitrogen, oxygen and sulfur. Any heteroatom with unsatisfied valency is assumed to have a hydrogen atom to satisfy the valency. Heterocyclyl includes saturated heterocyclic ring systems, which do not contain any double bonds within the rings, as well as unsaturated heterocyclic ring systems, which contain one or more, for example, 3 double bonds within a ring, provided that the resulting mono, bi or tricyclic ring system is stable, The heterocyclyl group may, for example, have 1 or 2 oxygen atoms and/or 1 or 2 sulfur atoms and/or 1 to 3 nitrogen atoms in the ring. Examples of heterocyclyls include pyrrolyl, pyrrolidinyl, pyrazolyl, imidazolyl, pyrazinyl, piperazinyl, oxazolyl, isoxazolyl, thiazolyl, furyl, thienyl, pyridyl, pyrimidyl, piperidyl, benzothiazolyl, purinyl, benzimidazolyl, benzooxazolyl, indolyl, isoindolyl, isoquinolyl, morpholinyl, quinoxalinyl, and quinolyl. Aromatic heterocyclyl groups may also be referred to by the customary term "heteroaryl" for which all the definitions and explanations relating to heterocyclyl apply. Examples of a 6-membered heteroaryl group containing 1 or 2 N atoms are pyridine, pyrimidine, pyridazine and pyrazine.

A substituted heterocyclyl refers to a heterocyclyl substituted with one or more groups selected from halogen, hydroxy, cyano, nitro, unsubstituted or substituted (d- Ci ₂)-alkyl, (C ₂-Ci ₂)-alkenyl, (C ₂-Ci ₂)-alkynyl, unsubstituted or substituted (C ₁-C ₁₂)- alkoxy, unsubstituted or substituted cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted aryloxy, heterocyclyl, -O-heterocyclyl, C(0)R _p, C(0)OR _p, SR _P, S(0)R _p, S0 ₂R _p, NRpRq and C(0)NR _pR _q; wherein R _p and R _q are independently selected from hydrogen, unsubstituted or substituted (C ₁-C ₁₂) alkyl, unsubstituted or substituted aryl, unsubstituted or substituted aralkyl and unsubstituted or substituted heterocyclyl or R _p and R _q together with the N to which they are attached optionally form a 3 to 7 membered ring.

The substituents may be present on either the ring carbon or the ring nitrogen atoms. The substituents can be present at one or more positions provided that a stable molecule results.

The term "halogen" refers to a fluorine, chlorine, bromine, or iodine atom.

The term "solvate" describes a complex wherein the compound is coordinated with a proportional amount of a solvent molecule. Specific solvates, wherein the solvent is water, are referred to as hydrates.

The term "tautomer" refers to the coexistence of two (or more) compounds that differ from each other only in the position of one (or more) mobile atoms and in electron distribution, for example, keto-enol tautomers.

Carboxylic acid isosteres refer to groups or molecules that have physical and chemical similarities to a carboxylic acid group, producing similar biological effects as those produced by a carboxylic acid group. Examples of carboxylic acid isosteres include groups selected from hydroxamic, acylcyanamide, phosphonate, sulfonate, sulfonamide, tetrazole, hydroxylisoxazole and oxadiazolone (The Practice of Medicinal Chemistry, Edited by Camille G. Wermuth, Second Edition, 2003, 189-214).

The term "N-oxide" as used herein refers to the oxide of the nitrogen atom of a nitrogen-containing heteroaryl or heterocycle. N-oxide can be formed in presence of an oxidizing agent for example peroxide such as m-chloro-perbenzoic acid or hydrogen peroxide. N-oxide is also known as amine-N-oxide, and is a chemical compound that contains N-»0 bond.

It will be understood that "substitution" or "substituted with" includes the implicit proviso that such substitution is in accordance with permitted valence of the substituted atom and the substituent, as well as represents a stable compound, which does not readily undergo undesired transformation such as by rearrangement, cyclization, or elimination.

As used herein, the term "compound of formula 1 " includes all the stereoisomeric and tautomeric forms and mixtures thereof in all ratios, and their pharmaceutically acceptable salts, solvates, polymorphs, prodrugs, carboxylic acid isosteres and N- oxides. Aspects of the Invention

In an aspect, the present invention provides provides compounds of formula 1 represented by compounds

Formula 1 a

in all their stereoisomeric and tautomeric forms; and their pharmaceutically acceptable salts, solvates, polymorphs, prodrugs, carboxylic acid isosteres and N-oxides;

wherein;

Z is selected from:

indicates the point of attachment;

n is an integer selected from 1 -5;

m is 0 or 1 ;

Ri and R ₂ are independently selected from hydrogen or (CrCi ₂)-alkyl, or R- _\ and R ₂ can optionally form an unsubstituted or substituted (C3-C7) cycloalkyl ring;

R ₃ is hydrogen or (CrCi ₂)-alkyl; R ₅ is selected from hydrogen, (CrCi ₂)-alkyl, CF ₃, (C ₃-C ₇)-cycloalkyl, aryl or heterocyclyl;

B is a 5-membered heteroaryl ring represented by any one of the general structures (i) to (x);

wherein 1 and 2 are the points of attachment of B to phenyl and to Z respectively and R ₄ is selected from hydrogen, (CrCi ₂)-alkyl or aryl; or B is a 6-membered heteroaryl ring containing 1 or 2 N-atoms, wherein the 6-membered heteroaryl ring may be unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (CrCi ₂)-alkoxy, cyano, nitro, (CrCi ₂)-alkyl, (C ₂-Ci ₂)-alkenyl, (C ₂-Ci ₂)-alkynyl, (C ₃-Ci ₂)- cycloalkyl, aryl, aryloxy, heterocyclyl or O-heterocyclyl; and

A is selected from (Ci-Ci ₂)-alkyl, (C ₃-Ci ₂)-cycloalkyl, aryl or heterocyclyl; wherein,

(Ci-Ci ₂)-alkyl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (Ci-Ci ₂)-alkoxy, cyano, nitro, (C ₃-Ci ₂)-cycloalkyl, aryl, heterocyclyl, C(0)Rp, C(0)OR _p, NRpRq, C(0)NR _pR _q, SR _P, S(0)R _p or S0 ₂R _p;

(C ₃-Ci ₂)-cycloalkyl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (Ci-Ci ₂)-alkoxy cyano, nitro, aryl, heterocyclyl, C(0)R _p, C(0)OR _p, NR _pRq, C(0)NR _pR _q, SR _P, S(0)R _p or S0 ₂R _p;

aryl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (Ci-Ci ₂)-alkoxy, cyano, nitro, (CrCi ₂)-alkyl, OCF ₃, CF ₃, (C ₂-Ci ₂)-alkenyl, (C ₂- Ci ₂)-alkynyl, (C ₃-Ci ₂)-cycloalkyl, aryl, aryloxy, heterocyclyl, O-heterocyclyl, C(0)R _p, C(0)OR _p, NR _pRq, C(0)NRpR _q, SR _P, S(0)R _p or S0 ₂R _p; or aryl may be fused with an unsubstituted or substituted 5 or 6-membered cycloalkyi ring optionally containing one or more heteroatoms selected from O, N or S; heterocyclyl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (CrCi ₂)-alkoxy, cyano, nitro, (CrCi ₂)-alkyl, (C ₂-Ci ₂)-alkenyl, (C ₂- Ci ₂)-alkynyl, (C ₃-Ci ₂)-cycloalkyl, aryl, aryloxy, heterocyclyl, O-heterocyclyl, C(0)R _p, C(0)OR _p, NRpRq, C(0)NRpR _q, SR _P, S(0)R _p or S0 ₂R _p;

with the proviso that A is not a methyl group. In a second aspect, the present invention provides compounds of formula 1 represented by compounds of formula 1 a, wherein,

B is

wherein 1 and 2 are the points of attachment of B to phenyl and to Z respectively;

Z is

indicates the point of attachment;

n is an integer selected from 1 -5; m is 0 or 1 ;

Ri and R ₂ are independently selected from hydrogen or (CrCi ₂)-alkyl, or and R ₂ optionally form an unsubstituted or substituted (C ₃-C ₇) cycloalkyi ring;

R ₃ is hydrogen or (CrCi ₂)-alkyl;

R ₅ is selected from hydrogen, (CrCi ₂)-alkyl, CF ₃, (C ₃-C ₇)-cycloalkyl, aryl heterocyclyl; and

A is selected from (CrCi ₂)-alkyl, (C ₃-Ci ₂)-cycloalkyl, aryl or heterocyclyl; wherein,

(Ci-Ci ₂)-alkyl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (Ci-Ci ₂)-alkoxy, cyano, (C ₃-Ci ₂)-cycloalkyl, aryl or heterocyclyl;

(C ₃-Ci ₂)-cycloalkyl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (Ci-Ci ₂)-alkoxy, cyano, aryl or heterocyclyl;

aryl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (Ci-Ci ₂)-alkoxy, cyano, (CrCi ₂)-alkyl, OCF ₃, CF ₃, (C ₃-Ci ₂)-cycloalkyl, aryl, aryloxy, heterocyclyl or O-heterocyclyl; or aryl may be fused with an unsubstituted or substituted 5 or 6-membered cycloalkyi ring optionally containing one or more heteroatoms selected from O, N or S;

heterocyclyl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (Ci-Ci ₂)-alkoxy, cyano, (CrCi ₂)-alkyl, (C ₃-Ci ₂)-cycloalkyl, aryl, aryloxy, heterocyclyl or O-heterocyclyl;

with the proviso that A is not a methyl group.

In an embodiment of the second aspect, the present invention provides compounds of formula 1 represented by compounds of formula 1 a, wherein

B and A are as defined in the second aspect of the invention;

Z is

indicates the point of attachment;

n is an integer selected from 1 -5;

Ri and R ₂ are independently selected from hydrogen or (CrCi ₂)-alkyl, or R- _\ and R ₂ can optionally form an unsubstituted or substituted (C ₃-C ₇) cycloalkyi ring; and R ₃ is hydrogen or (CrCi ₂)-alkyl;

with the proviso that A is not a methyl group.

In another embodiment of the second aspect, the present invention provides compounds of formula 1 represented by compounds of formula 1 a, wherein

B and A are as defined in the second aspect of the invention;

Z is

H O

NN,^ R ₅

R ₂

indicates the point of attachment;

n is an integer selected from 1 -5;

Ri and R ₂ are independently selected from hydrogen or (CrCi ₂)-alkyl, or R- _\ and R ₂ can optionally form an unsubstituted or substituted (C ₃-C ₇) cycloalkyl ring; and

R ₅ is selected from hydrogen, (CrCi ₂)-alkyl, CF ₃, (C ₃-C ₇)-cycloalkyl, aryl or heterocyclyl;

with the proviso that A is not a methyl group.

In another embodiment of the second aspect, the present invention provides compounds of formula 1 represented by compounds of formula 1 a, wherein

B and A are as defined in the second aspect of the invention;

Z is

indicates the point of attachment;

n is an integer selected from 1 -5;

Ri and R ₂ are independently selected from hydrogen or (CrCi ₂)-alkyl, or R- _\ and R ₂ can optionally form an unsubstituted or substituted (C ₃-C ₇) cycloalkyl ring; and

R ₅ is selected from hydrogen, (CrCi ₂)-alkyl, CF ₃, (C ₃-C ₇)-cycloalkyl, aryl or heterocyclyl;

with the proviso that A is not a methyl group. In another embodiment of the second aspect, the present invention provides compounds of formula 1 represented by compounds of formula 1 a, wherein

B and A are as defined in the second aspect of the invention;

Z is

indicates the point of attachment;

n is an integer selected from 1 -5;

Ri and R ₂ are independently selected from hydrogen or (CrCi ₂)-alkyl, or R- _\ and R ₂ can optionally form an unsubstituted or substituted (C ₃-C ₇) cycloalkyl ring;

with the proviso that A is not a methyl group.

In another embodiment of the second aspect, the present invention provides compounds of formula 1 represented by compounds of formula 1 a, wherein

B and A are as defined in the second aspect of the invention;

Z is

indicates the point of attachment;

m is 0 or 1 ;

Ri and R ₂ are independently selected from hydrogen or (CrCi ₂)-alkyl, or R- _\ and R ₂ can optionally form an unsubstituted or substituted (C ₃-C ₇) cycloalkyl ring; and

R ₃ is hydrogen or (Ci-Ci ₂)-alkyl;

with the proviso that A is not a methyl group.

In another embodiment of the second aspect, the present invention provides compounds of formula 1 represented by compounds of formula 1 a, wherein

B and A are as defined in the second aspect of the invention;

Z is

indicates the point of attachment; m is 0 or 1 ;

Ri and R ₂ are independently selected from hydrogen or (CrCi ₂)-alkyl, or R- _\ and R ₂ can optionally form an unsubstituted or substituted (C ₃-C ₇) cycloalkyl ring;

with the proviso that A is not a methyl group.

In another embodiment of the second aspect, the present invention provides compounds of formula 1 represented by compounds of formula 1 a, wherein

B and A are as defined in the second aspect of the invention;

Z is

indicates the point of attachment;

m is 0 or 1 ;

Ri and R ₂ are independently selected from hydrogen or (CrCi ₂)-alkyl, or R- _\ and R ₂ can optionally form an unsubstituted or substituted (C ₃-C ₇) cycloalkyl ring;

with the proviso that A is not a methyl group.

In another embodiment of the second aspect, the present invention provides compounds of formula 1 represented by compounds of formula 1 a, wherein

B and A are as defined in the second aspect of the invention;

Z is

indicates the point of attachment;

m is 0 or 1 ;

Ri and R ₂ are independently selected from hydrogen or (CrCi ₂)-alkyl, or R- _\ and R ₂ can optionally form an unsubstituted or substituted (C ₃-C ₇) cycloalkyl ring;

with the proviso that A is not a methyl group.

In another embodiment of the second aspect, the present invention provides compounds of formula 1 represented by compounds of formula 1 a, wherein

B and A are as defined in the second aspect of the invention; Z is

indicates the point of attachment;

m is 0 or 1 ;

Ri and R ₂ are independently selected from hydrogen or (CrCi ₂)-alkyl, or R- _\ and R ₂ can optionally form an unsubstituted or substituted (C ₃-C ₇) cycloalkyl ring;

with the proviso that A is not a methyl group.

In another embodiment of the second aspect, the present invention provides compounds of formula 1 represented by compounds of formula 1 a, wherein

B and A are as defined in the second aspect of the invention;

Z is

indicates the point of attachment;

m is 0 or 1 ;

Ri and R ₂ are independently selected from hydrogen or (CrCi ₂)-alkyl, or R- _\ and R ₂ can optionally form an unsubstituted or substituted (C ₃-C ₇) cycloalkyl ring;

with the proviso that A is not a methyl group.

In another embodiment of the second aspect, the present invention provides compounds of formula 1 represented by compounds of formula 1 a, wherein

B and A are as defined in the second aspect of the invention;

Z is

indicates the point of attachment;

m is 0 or 1 ;

Ri and R ₂ are independently selected from hydrogen or (CrCi ₂)-alkyl, or R- _\ and R ₂ can optionally form an unsubstituted or substituted (C ₃-C ₇) cycloalkyl ring; and R ₅ is selected from hydrogen, (CrCi ₂)-alkyl, CF ₃, (C ₃-C ₇)-cycloalkyl, aryl or heterocyclyl;

with the proviso that A is not a methyl group.

In another embodiment of the second aspect, the present invention provides compounds of formula 1 represented by compounds of formula 1 a, wherein

B and A are as defined in the second aspect of the invention;

Z is

indicates the point of attachment;

m is 0 or 1 ;

Ri and R ₂ are independently selected from hydrogen or (CrCi ₂)-alkyl, or R- _\ and R ₂ can optionally form an unsubstituted or substituted (C ₃-C ₇) cycloalkyl ring;

with the proviso that A is not a methyl group.

In another embodiment of the second aspect, the present invention provides compounds of formula 1 represented by compounds of formula 1 a, wherein

B and A are as defined in the second aspect of the invention;

Z is

indicates the point of attachment;

m is 0 or 1 ;

Ri and R ₂ are independently selected from hydrogen or (CrCi ₂)-alkyl, or R- _\ and R ₂ can optionally form an unsubstituted or substituted (C ₃-C ₇) cycloalkyl ring;

with the proviso that A is not a methyl group.

In another embodiment of the second aspect, the present invention provides compounds of formula 1 represented by compounds of formula 1 a, wherein

B and A are as defined in the second aspect of the invention;

Z is

indicates the point of attachment;

m is 0 or 1 ;

Ri and R ₂ are independently selected from hydrogen or (CrCi ₂)-alkyl, or R- _\ and R ₂ can optionally form an unsubstituted or substituted (C ₃-C ₇) cycloalkyl ring; and

R ₃ is hydrogen or (CrCi ₂)-alkyl;

with the proviso that A is not a methyl group.

In another embodiment of the second aspect, the present invention provides compounds of formula 1 represented by compounds of formula 1 a, wherein

B and A are as defined in the second aspect of the invention;

Z is

indicates the point of attachment;

m is 0 or 1 ;

Ri and R ₂ are independently selected from hydrogen or (CrCi ₂)-alkyl, or R- _\ and R ₂ can optionally form an unsubstituted or substituted (C ₃-C ₇) cycloalkyl ring; and

R ₅ is selected from hydrogen, (CrCi ₂)-alkyl, CF ₃, (C ₃-C ₇)-cycloalkyl, aryl or heterocyclyl;

with the proviso that A is not a methyl group.

In another embodiment of the second aspect, the present invention provides compounds of formula 1 represented by compounds of formula 1 a, wherein

B and A are as defined in the second aspect of the invention;

Z is

indicates the point of attachment;

m is 0 or 1 ; and R ₅ is selected from hydrogen, (CrCi ₂)-alkyl, CF ₃, (C ₃-C ₇)-cycloalkyl, aryl or heterocyclyl;

with the proviso that A is not a methyl group. In another embodiment of the second aspect, the present invention provides compounds of formula 1 represented by compounds of formula 1 a, wherein

B and A are as defined in the second aspect of the invention;

Z is

indicates the point of attachment;

m is 0 or 1 ;

Ri and R ₂ are independently selected from hydrogen or (CrCi ₂)-alkyl, or R- _\ and R ₂ can optionally form an unsubstituted or substituted (C ₃-C ₇) cycloalkyl ring; and

R ₃ is hydrogen or (Ci-Ci ₂)-alkyl;

with the proviso that A is not a methyl group.

In a third aspect, the present invention provides compounds of formula 1 represented by compounds of formula 1 a; wherein,

B is

wherein 1 and 2 are the points of attachment of B to phenyl and to Z respectively;

Z is selected from:

indicates the point of attachment;

n is an integer selected from 1 -5;

m is 0 or 1 ;

Ri and R ₂ are independently selected from hydrogen or (CrCi ₂)-alkyl, or R- _\ and R ₂ can optionally form an unsubstituted or substituted (C ₃-C ₇) cycloalkyi ring;

R ₃ is hydrogen or (CrCi ₂)-alkyl;

R ₅ is selected from hydrogen, (CrCi ₂)-alkyl, CF ₃, (C ₃-C ₇)-cycloalkyl, aryl, or heterocyclyl; and

A is selected from (Ci-Ci ₂)-alkyl, (C ₃-Ci ₂)-cycloalkyl, aryl or heterocyclyl; wherein,

(Ci-Ci ₂)-alkyl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (Ci-Ci ₂)-alkoxy, cyano, (C ₃-Ci ₂)-cycloalkyl, aryl or heterocyclyl;

(C ₃-Ci ₂)-cycloalkyl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (Ci-Ci ₂)-alkoxy, cyano, aryl or heterocyclyl;

with the proviso that A is not a methyl group. In a fourth aspect, the present invention provides compounds of formula 1 represented by compounds of formula 1 a; wherein,

B is

wherein 1 and 2 are the points of attachment of B to phenyl and to Z respectively;

Z is selected from:

indicates the point of attachment;

n is an integer selected from 1 -5;

m is 0 or 1 ;

Ri and R ₂ are independently selected from hydrogen or (CrCi ₂)-alkyl, or R- _\ and R ₂ can optionally form an unsubstituted or substituted (C ₃-C ₇) cycloalkyl ring;

R ₃ is hydrogen or (CrCi ₂)-alkyl;

R ₅ is selected from hydrogen, (CrCi ₂)-alkyl, CF ₃, (C ₃-C ₇)-cycloalkyl, aryl, or heterocyclyl; and

A is selected from (Ci-Ci ₂)-alkyl, (C ₃-Ci ₂)-cycloalkyl, aryl or heterocyclyl; wherein,

(CrCi ₂)-alkyl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (CrCi ₂)-alkoxy, cyano, (C ₃-Ci ₂)-cycloalkyl, aryl or heterocyclyl;

(C ₃-Ci ₂)-cycloalkyl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (Ci-Ci ₂)-alkoxy, cyano, aryl or heterocyclyl;

with the proviso that A is not a methyl group.

In a fifth aspect, the present invention provides compounds of formula 1 represented by compounds of formula 1 a; wherein,

B is

wherein 1 and 2 are the points of attachment of B to phenyl and to Z respectively;

Z is selected from:

indicates the point of attachment;

n is an integer selected from 1 -5;

m is 0 or 1 ;

Ri and R ₂ are independently selected from hydrogen or (CrCi ₂)-alkyl, or R- _\ and R ₂ can optionally form an unsubstituted or substituted (C ₃-C ₇) cycloalkyi ring;

R ₃ is hydrogen or (CrCi ₂)-alkyl;

R ₅ is selected from hydrogen, (CrCi ₂)-alkyl, CF ₃, (C ₃-C ₇)-cycloalkyl, aryl, or heterocyclyl; and

A is selected from (Ci-Ci ₂)-alkyl, (C ₃-Ci ₂)-cycloalkyl, aryl or heterocyclyl; wherein,

(Ci-Ci ₂)-alkyl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (Ci-Ci ₂)-alkoxy, cyano, (C ₃-Ci ₂)-cycloalkyl, aryl or heterocyclyl;

(C ₃-Ci ₂)-cycloalkyl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (Ci-Ci ₂)-alkoxy, cyano, aryl or heterocyclyl;

aryl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (Ci-Ci ₂)-alkoxy, cyano, (CrCi ₂)-alkyl, OCF ₃, CF ₃, (C ₃-Ci ₂)-cycloalkyl, aryl, aryloxy, heterocyclyl or O-heterocyclyl, or aryl may be fused with an unsubstituted or substituted 5 or 6-membered cycloalkyi ring optionally containing one or more heteroatoms selected from O, N or S;

with the proviso that A is not a methyl group.

In a sixth aspect, the present invention provides compounds of formula 1 represented by compounds of formula 1 b,

Formula 1 b

in all their stereoisomeric and tautomeric forms; and their pharmaceutically acceptable salts, solvates, polymorphs, prodrugs, carboxylic acid isosteres and N-oxides;

wherein,

Z is selected from:

indicates the point of attachment;

n is an integer selected from 1 -5;

m is 0 or 1 ;

Ri and R ₂ are independently selected from hydrogen or (CrCi ₂)-alkyl, or R- _\ and R ₂ can optionally form an unsubstituted or substituted (C ₃-C ₇) cycloalkyl ring;

R ₃ is hydrogen or (CrCi ₂)-alkyl;

R ₅ is selected from hydrogen, (CrCi ₂)-alkyl, CF ₃, (C ₃-C ₇)-cycloalkyl, aryl, or heterocyclyl;

B is a 5-membered heteroaryl ring represented by any one of the general structures (i) to (x);

wherein 1 and 2 are the points of attachment of B to phenyl and to Z respectively and R ₄ is selected from hydrogen, (CrCi ₂)-alkyl or aryl; or B is a 6-membered heteroaryl ring containing 1 or 2 N-atoms, wherein the 6-membered heteroaryl ring may be unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (CrCi ₂)-alkoxy, cyano, nitro, (CrCi ₂)-alkyl, (C ₂-Ci ₂)-alkenyl, (C ₂-Ci ₂)-alkynyl, (C ₃-Ci ₂)- cycloalkyl, aryl, aryloxy, heterocyclyl or O-heterocyclyl; and

A is selected from (Ci-Ci ₂)-alkyl, (C ₃-Ci ₂)-cycloalkyl, aryl or heterocyclyl; wherein,

(Ci-Ci ₂)-alkyl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (Ci-Ci ₂)-alkoxy, cyano, nitro, (C ₃-Ci ₂)-cycloalkyl, aryl, heterocyclyl, C(0)Rp, C(0)OR _p, NRpRq, C(0)NR _pR _q, SR _P, S(0)R _p or S0 ₂R _p;

(C ₃-Ci ₂)-cycloalkyl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (Ci-Ci ₂)-alkoxy, cyano, nitro, aryl, heterocyclyl, C(0)R _p, C(0)OR _p, NR _pRq, C(0)NR _pR _q, SR _P, S(0)R _p or S0 ₂R _p;

heterocyclyl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (Ci-Ci ₂)-alkoxy, cyano, nitro, (CrCi ₂)-alkyl, (C ₂-Ci ₂)-alkenyl, (C ₂- Ci ₂)-alkynyl, (C ₃-Ci ₂)-cycloalkyl, aryl, aryloxy, heterocyclyl, O-heterocyclyl, C(0)R _p, C(0)OR _p, NR _pRq, C(0)NRpR _q, SR _P, S(0)R _p or S0 ₂R _p; R _p and R _q are independently selected from hydrogen, (CrCi ₂)-alkyl, aryl, aralkyi or heterocyclyl, or R _p and R _q together with the N to which they are attached optionally form a 3 to 7 membered ring;

with the proviso that A is not a methyl group.

In a seventh aspect, the present invention provides compounds of formula 1 represented by compounds of formula 1 b, wherein,

B is

wherein 1 and 2 are the points of attachment of B to phenyl and to Z respectively;

Z is

indicates the point of attachment;

n is an integer selected from 1 -5;

m is 0 or 1 ;

Ri and R ₂ are independently selected from hydrogen or (CrCi ₂)-alkyl, or R- _\ and R ₂ can optionally form an unsubstituted or substituted (C ₃-C ₇) cycloalkyl ring;

R ₃ is hydrogen or (Ci-Ci ₂)-alkyl; R ₅ is selected from hydrogen, (CrCi ₂)-alkyl, CF ₃, (C ₃-C ₇)-cycloalkyl, aryl or heterocyclyl; and

A is selected from (CrCi ₂)-alkyl, (C ₃-Ci ₂)-cycloalkyl, aryl or heterocyclyl; wherein,

(CrCi ₂)-alkyl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (Ci-Ci ₂)-alkoxy, cyano, (C ₃-Ci ₂)-cycloalkyl, aryl or heterocyclyl;

(C ₃-Ci ₂)-cycloalkyl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (Ci-Ci ₂)-alkoxy, cyano, aryl or heterocyclyl;

with the proviso that A is not a methyl group. In an embodiment of the seventh aspect, Z is

indicates the point of attachment;

n is an integer selected from 1 -5;

Ri and R ₂ are independently selected from hydrogen or (CrCi ₂)-alkyl, or R- _\ and R ₂ can optionally form an unsubstituted or substituted (C ₃-C ₇) cycloalkyi ring;

R ₃ is hydrogen or (Ci-Ci ₂)-alkyl; and B and A are as defined above

with the proviso that A is not a methyl group.

In another embodiment of the seventh aspect, Z is

indicates the point of attachment; n is an integer selected from 1 -5;

Ri and R ₂ are independently selected from hydrogen or (CrCi ₂)-alkyl, or R- _\ and R ₂ optionally form an unsubstituted or substituted (C ₃-C ₇) cycloalkyi ring;

R ₅ is selected from hydrogen, (CrCi ₂)-alkyl, CF ₃, (C ₃-C ₇)-cycloalkyl, aryl, heterocyclyl; and B and A are as defined in the seventh aspect,

with the proviso that A is not a methyl group.

In another embodiment of the seventh aspect, Z is

indicates the point of attachment;

n is an integer selected from 1 -5;

Ri and R ₂ are independently selected from hydrogen or (CrCi ₂)-alkyl, or R- _\ and R ₂ can optionally form an unsubstituted or substituted (C ₃-C ₇) cycloalkyi ring;

R ₅ is selected from hydrogen, (CrCi ₂)-alkyl, CF ₃, (C ₃-C ₇)-cycloalkyl, aryl, or heterocyclyl; and B and A are as defined in the seventh aspect,

with the proviso that A is not a methyl group.

In another embodiment of the seventh aspect, Z is

indicates the point of attachment;

n is an integer selected from 1 -5;

Ri and R ₂ are independently selected from hydrogen or (CrCi ₂)-alkyl, or R- _\ and R ₂ can optionally form an unsubstituted or substituted (C ₃-C ₇) cycloalkyi ring; and B and A are as defined in the seventh aspect,

with the proviso that A is not a methyl group.

In another embodiment of the seventh aspect, Z is

indicates the point of attachment; m is 0 or 1 ;

Ri and R ₂ are independently selected from hydrogen or (CrCi ₂)-alkyl, or R- _\ and R ₂ can optionally form an unsubstituted or substituted (C ₃-C ₇) cycloalkyi ring;

R ₃ is hydrogen or (CrCi ₂)-alkyl; and B and A are as defined in the seventh aspect, with the proviso that A is not a methyl group.

In another embodiment of the seventh aspect, Z is

indicates the point of attachment;

m is 0 or 1 ;

with the proviso that A is not a methyl group.

In another embodiment of the seventh aspect, Z is

indicates the point of attachment;

m is 0 or 1 ;

with the proviso that A is not a methyl group.

In another embodiment of the seventh aspect, Z is

indicates the point of attachment;

m is 0 or 1 ; Ri and R ₂ are independently selected from hydrogen or (CrCi ₂)-alkyl, or R- _\ and R ₂ can optionally form an unsubstituted or substituted (C ₃-C ₇) cycloalkyi ring; and B and A are as defined in the seventh aspect,

with the proviso that A is not a methyl group.

In another embodiment of the seventh aspect, Z is

indicates the point of attachment;

m is 0 or 1 ;

Ri and R ₂ are independently selected from hydrogen or (CrCi ₂)-alkyl, or Ri and R ₂ can optionally form an unsubstituted or substituted (C ₃-C ₇) cycloalkyi ring; and B and A are as defined in the seventh aspect,

with the proviso that A is not a methyl group.

In another embodiment of the seventh aspect, Z is

indicates the point of attachment;

m is 0 or 1 ;

with the proviso that A is not a methyl group.

In another embodiment of the seventh aspect, Z is

indicates the point of attachment;

m is 0 or 1 ;

Ri and R ₂ are independently selected from hydrogen or (CrCi ₂)-alkyl, or R- _\ and R ₂ can optionally form an unsubstituted or substituted (C ₃-C ₇) cycloalkyi ring; R ₅ is selected from hydrogen, (CrCi ₂)-alkyl, CF ₃, (C ₃-C ₇)-cycloalkyl, aryl, or heterocyclyl; and B and A are as defined in the seventh aspect,

with the proviso that A is not a methyl group.

In another embodiment of th , Z is

indicates the point of attachment;

m is 0 or 1 ;

with the proviso that A is not a methyl group.

In another embodiment of th , Z is

indicates the point of attachment;

m is 0 or 1 ;

with the proviso that A is not a methyl group.

In another embodiment of the seventh aspect, Z is

indicates the point of attachment;

m is 0 or 1 ;

Ri and R ₂ are independently selected from hydrogen or (CrCi ₂)-alkyl, or R- _\ and R ₂ can optionally form an unsubstituted or substituted (C ₃-C ₇) cycloalkyi ring;

R ₃ is hydrogen or (Ci-Ci ₂)-alkyl; and B and A are as defined in the seventh aspect, with the proviso that A is not a methyl group. In another embodiment of the seventh aspect, Z is

indicates the point of attachment;

m is 0 or 1 ;

Ri and R ₂ are independently selected from hydrogen or (CrCi ₂)-alkyl, or R- _\ and R ₂ optionally form an unsubstituted or substituted (C ₃-C ₇) cycloalkyl ring;

R ₅ is selected from hydrogen, (CrCi ₂)-alkyl, CF ₃, (C ₃-C ₇)-cycloalkyl, aryl, heterocyclyl; and B and A are as defined in the seventh aspect,

with the proviso that A is not a methyl group.

In another embodiment of the seventh as ect, Z is

indicates the point of attachment;

R ₅ is selected from hydrogen, (CrCi ₂)-alkyl, CF ₃, (C ₃-C ₇)-cycloalkyl, aryl, and heterocyclyl; and B and A are as defined in the seventh aspect,

with the proviso that A is not a methyl group.

In another embodiment of the seventh as ect, Z is

indicates the point of attachment;

m is 0 or 1 ;

Ri and R ₂ are independently selected from hydrogen or (CrCi ₂)-alkyl, or R- _\ and R ₂ can optionally form an unsubstituted or substituted (C ₃-C ₇) cycloalkyl ring;

R ₃ is hydrogen or (Ci-Ci ₂)-alkyl; and B and A are as defined in the seventh aspect, with the proviso that A is not a methyl group.

In an eighth aspect, the present invention provides compounds of formula 1 represented by compounds of formula 1 b; wherein, B is

wherein 1 and 2 are the points of attachment of B to phenyl and to Z respectively;

Z is selected from:

indicates the point of attachment;

n is an integer selected from 1 -5;

m is 0 or 1 ;

Ri and R ₂ are independently selected from hydrogen or (CrCi ₂)-alkyl, or R- _\ and R ₂ can optionally form an unsubstituted or substituted (C ₃-C ₇) cycloalkyl ring;

R ₃ is hydrogen or (CrCi ₂)-alkyl;

R ₅ is selected from hydrogen, (CrCi ₂)-alkyl, CF ₃, (C ₃-C ₇)-cycloalkyl, aryl, or heterocyclyl; and

A is selected from (CrCi ₂)-alkyl, (C ₃-Ci ₂)-cycloalkyl, aryl or heterocyclyl; wherein,

(Ci-Ci ₂)-alkyl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (Ci-Ci ₂)-alkoxy, cyano, (C ₃-Ci ₂)-cycloalkyl, aryl or heterocyclyl; (C ₃-Ci ₂)-cycloalkyl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (CrCi ₂)-alkoxy, cyano, aryl or heterocyclyl;

aryl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (CrCi ₂)-alkoxy, cyano, (CrCi ₂)-alkyl, OCF ₃, CF ₃, (C ₃-Ci ₂)-cycloalkyl, aryl, aryloxy, heterocyclyl or O-heterocyclyl; or aryl may be fused with an unsubstituted or substituted 5 or 6-membered cycloalkyi ring optionally containing one or more heteroatoms selected from O, N or S;

with the proviso that A is not a methyl group.

In a ninth aspect, the present invention provides compounds of formula 1 represented by compounds of formula 1 b; wherein,

B is

wherein 1 and 2 are the points of attachment of B to phenyl and to Z respectively; Z is selected from:

indicates the point of attachment;

n is an integer selected from 1 -5;

m is 0 or 1 ;

Ri and R ₂ are independently selected from hydrogen or (CrCi ₂)-alkyl, or R- _\ and R ₂ can optionally form an unsubstituted or substituted (C ₃-C ₇) cycloalkyi ring;

R ₃ is hydrogen or (CrCi ₂)-alkyl;

R ₅ is selected from hydrogen, (CrCi ₂)-alkyl, CF ₃, (C ₃-C ₇)-cycloalkyl, aryl, or heterocyclyl; and

A is selected from (Ci-Ci ₂)-alkyl, (C ₃-Ci ₂)-cycloalkyl, aryl or heterocyclyl; wherein,

(Ci-Ci ₂)-alkyl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (Ci-Ci ₂)-alkoxy, cyano, (C ₃-Ci ₂)-cycloalkyl, aryl or heterocyclyl;

(C ₃-Ci ₂)-cycloalkyl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (Ci-Ci ₂)-alkoxy, cyano, aryl or heterocyclyl;

aryl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (Ci-Ci ₂)-alkoxy, cyano, (CrCi ₂)-alkyl, OCF ₃, CF ₃, (C ₃-Ci ₂)-cycloalkyl, aryl, aryloxy, heterocyclyl or O-heterocyclyl, or aryl may be fused with an unsubstituted or substituted 5 or 6-membered cycloalkyi ring optionally containing one or more heteroatoms selected from O, N or S;

with the proviso that A is not a methyl group.

In a tenth aspect, the present invention provides compounds of formula 1 represented by compounds of formula 1 b; wherein,

B is

wherein 1 and 2 are the points of attachment of B to phenyl and to Z respectively; Z is selected from:

indicates the point of attachment;

n is an integer selected from 1 -5;

m is 0 or 1 ;

Ri and R ₂ are independently selected from hydrogen or (CrCi ₂)-alkyl, or R- _\ and R ₂ can optionally form an unsubstituted or substituted (C ₃-C ₇) cycloalkyl ring;

R ₃ is hydrogen or (CrCi ₂)-alkyl;

R ₅ is selected from hydrogen, (CrCi ₂)-alkyl, CF ₃, (C ₃-C ₇)-cycloalkyl, aryl, or heterocyclyl; and

A is selected from (CrCi ₂)-alkyl, (C ₃-Ci ₂)-cycloalkyl, aryl or heterocyclyl; wherein,

(Ci-Ci ₂)-alkyl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (Ci-Ci ₂)-alkoxy, cyano, (C ₃-Ci ₂)-cycloalkyl, aryl or heterocyclyl; (C ₃-Ci ₂)-cycloalkyl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (CrCi ₂)-alkoxy, cyano, aryl or heterocyclyl;

aryl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (CrCi ₂)-alkoxy, cyano, (CrCi ₂)-alkyl, OCF ₃, CF ₃, (C ₃-Ci ₂)-cycloalkyl, aryl, aryloxy, heterocyclyl or O-heterocyclyl, or aryl may be fused with an unsubstituted or substituted 5 or 6-membered cycloalkyi ring optionally containing one or more heteroatoms selected from O, N and S;

with the proviso that A is not a methyl group.

In an eleventh aspect, the present invention provides compounds of formula 1 represented by compounds of

Formula 1 c

in all their stereoisomeric and tautomeric forms; and their pharmaceutically acceptable salts, solvates, polymorphs, prodrugs, carboxylic acid isosteres and N-oxides;

wherein,

Z is selected from:

indicates the point of attachment;

n is an integer selected from 1 -5;

m is 0 or 1 ;

Ri and R ₂ are independently selected from hydrogen or (CrCi ₂)-alkyl, or R- _\ and R ₂ can optionally form an unsubstituted or substituted (C ₃-C ₇) cycloalkyl ring;

R ₃ is hydrogen or (CrCi ₂)-alkyl;

R ₅ is selected from hydrogen, (CrCi ₂)-alkyl, CF ₃, (C ₃-C ₇)-cycloalkyl, aryl, or heterocyclyl;

B is a 5-membered heteroaryl ring represented by any one of the general structures (i) to (x);

wherein 1 and 2 are the points of attachment of B to phenyl and to Z respectively and R ₄ is selected from hydrogen, (Ci-Ci ₂)-alkyl or aryl; or B is a 6-membered heteroaryl ring containing 1 or 2 N-atoms, wherein the 6-membered heteroaryl ring may be unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (Ci-Ci ₂)-alkoxy, cyano, nitro, (Ci-Ci ₂)-alkyl, (C ₂-Ci ₂)-alkenyl, (C ₂-Ci ₂)-alkynyl, (C ₃-Ci ₂)- cycloalkyl, aryl, aryloxy, heterocyclyl or O-heterocyclyl; and

A is selected from (Ci-Ci ₂)-alkyl, (C ₃-Ci ₂)-cycloalkyl, aryl or heterocyclyl; wherein, (CrCi ₂)-alkyl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (CrCi ₂)-alkoxy, cyano, nitro, (C ₃-Ci ₂)-cycloalkyl, aryl, heterocyclyl, C(0)R _p, C(0)OR _p, NRpRq, C(0)NR _pR _q, SR _P, S(0)R _p or S0 ₂R _p;

aryl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (Ci-Ci ₂)-alkoxy, cyano, nitro, (Ci-Ci ₂)-alkyl, OCF ₃, CF ₃, (C ₂-Ci ₂)-alkenyl, (C ₂- Ci ₂)-alkynyl, (C ₃-Ci ₂)-cycloalkyl, aryl, aryloxy, heterocyclyl, O-heterocyclyl, C(0)R _p, C(0)OR _p, NRpRq, C(0)NRpR _q, SR _P, S(0)R _p or S0 ₂R _p; or aryl may be fused with an unsubstituted or substituted 5 or 6-membered cycloalkyl ring optionally containing one or more heteroatoms selected from O, N or S;

R _p and R _q are independently selected from hydrogen, (Ci-Ci ₂)-alkyl, aryl, aralkyi or heterocyclyl, or R _p and R _q together with the N to which they are attached optionally form a 3 to 7 membered ring;

with the proviso that A is not a methyl group.

In a twelfth aspect, the present invention provides compounds of formula 1 represented by compounds of formula 1 c, wherein,

B is

wherein 1 and 2 are the points of attachment of B to phenyl and to Z respectively;

Z is

indicates the point of attachment;

n is an integer selected from 1 -5;

m is 0 or 1 ;

Ri and R ₂ are independently selected from hydrogen or (CrCi ₂)-alkyl, or and R ₂ can optionally form an unsubstituted or substituted (C ₃-C ₇) cycloalkyl ring;

R ₃ is hydrogen or (CrCi ₂)-alkyl;

R ₅ is selected from hydrogen, (CrCi ₂)-alkyl, CF ₃, (C ₃-C ₇)-cycloalkyl, aryl or heterocyclyl; and

A is selected from (Ci-Ci ₂)-alkyl, (C ₃-Ci ₂)-cycloalkyl, aryl or heterocyclyl; wherein,

(Ci-Ci ₂)-alkyl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (Ci-Ci ₂)-alkoxy, cyano, (C ₃-Ci ₂)-cycloalkyl, aryl or heterocyclyl;

(C ₃-Ci ₂)-cycloalkyl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (Ci-Ci ₂)-alkoxy, cyano, aryl or heterocyclyl;

aryl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (Ci-Ci ₂)-alkoxy, cyano, (Ci-Ci ₂)-alkyl, OCF ₃, CF ₃, (C ₃-Ci ₂)-cycloalkyl, aryl, aryloxy, heterocyclyl or O-heterocyclyl; or aryl may be fused with an unsubstituted or substituted 5 or 6-membered cycloalkyi ring optionally containing one or more heteroatoms selected from O, N or S;

heterocyclyl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (CrCi ₂)-alkoxy, cyano, (CrCi ₂)-alkyl, (C ₃-Ci ₂)-cycloalkyl, aryl, aryloxy, heterocyclyl or O-heterocyclyl;

with the proviso that A is not a methyl group.

In an embodiment of the twelfth aspect, Z is indicates the point of attachment;

n is an integer selected from 1 -5;

Ri and R ₂ are independently selected from hydrogen or (Ci-Ci ₂)-alkyl, or R- _\ and R ₂ can optionally form an unsubstituted or substituted (C ₃-C ₇) cycloalkyi ring;

R ₃ is hydrogen or (Ci-Ci ₂)-alkyl; and B and A are as defined in the twelfth aspect, with the proviso that A is not a methyl group.

In another embodiment of the twelfth aspect, Z is

indicates the point of attachment;

n is an integer selected from 1 -5;

Ri and R ₂ are independently selected from hydrogen or (Ci-Ci ₂)-alkyl, or R- _\ and R ₂ can optionally form an unsubstituted or substituted (C ₃-C ₇) cycloalkyi ring;

R ₅ is selected from hydrogen, (Ci-Ci ₂)-alkyl, CF ₃, (C ₃-C ₇)-cycloalkyl, aryl, or heterocyclyl; and B and A are as defined in the twelfth aspect,

with the proviso that A is not a methyl group.

In another embodiment of the twelfth aspect, Z is

indicates the point of attachment; n is an integer selected from 1 -5;

Ri and R ₂ are independently selected from hydrogen or (CrCi ₂)-alkyl, or R- _\ and R ₂ optionally form an unsubstituted or substituted (C ₃-C ₇) cycloalkyi ring;

R ₅ is selected from hydrogen, (CrCi ₂)-alkyl, CF ₃, (C ₃-C ₇)-cycloalkyl, aryl, heterocyclyl; and B and A are as defined in the twelfth aspect,

with the proviso that A is not a methyl group.

In another embodiment of the twelfth aspect, Z is

indicates the point of attachment;

n is an integer selected from 1 -5;

Ri and R ₂ are independently selected from hydrogen or (Ci-Ci ₂)-alkyl, or R- _\ and R ₂ can optionally form an unsubstituted or substituted (C ₃-C ₇) cycloalkyi ring; and B and A are as defined in the twelfth aspect,

with the proviso that A is not a methyl group.

In another embodiment of the twelfth aspect, Z is

indicates the point of attachment;

m is 0 or 1 ;

Ri and R ₂ are independently selected from hydrogen or (Ci-Ci ₂)-alkyl, or R- _\ and R ₂ can optionally form an unsubstituted or substituted (C ₃-C ₇) cycloalkyi ring;

R ₃ is hydrogen or (Ci-Ci ₂)-alkyl; and B and A are as defined in the twelfth aspect, with the proviso that A is not a methyl group.

In another embodiment of the twelfth aspect, Z is

indicates the point of attachment;

with the proviso that A is not a methyl group.

In another embodiment of the twelfth aspect, Z is

indicates the point of attachment;

m is 0 or 1 ;

with the proviso that A is not a methyl group.

In another embodiment of the twelfth aspect, Z is

indicates the point of attachment;

m is 0 or 1 ;

with the proviso that A is not a methyl group.

In another embodiment of the twelfth aspect, Z is

indicates the point of attachment;

with the proviso that A is not a methyl group.

In another embodiment of the twelfth aspect, Z is

indicates the point of attachment;

m is 0 or 1 ;

with the proviso that A is not a methyl group.

In another embodiment of the twelfth aspect, Z is

indicates the point of attachment;

m is 0 or 1 ;

Ri and R ₂ are independently selected from hydrogen or (Ci-Ci ₂)-alkyl, or R- _\ and R ₂ can optionally form an unsubstituted or substituted (C ₃-C ₇) cycloalkyi ring;

R ₅ is selected from hydrogen, (Ci-Ci ₂)-alkyl, CF ₃, (C ₃-C ₇)-cycloalkyl, aryl, or heterocyclyl; and B and A are as defined in the twelfth aspect,

with the proviso that A is not a methyl group.

In another embodiment of th , Z is

indicates the point of attachment;

with the proviso that A is not a methyl group.

In another embodiment of th , Z is

indicates the point of attachment;

m is 0 or 1 ;

with the proviso that A is not a methyl group.

In another embodiment of the twelfth aspect, Z is

indicates the point of attachment;

m is 0 or 1 ;

Ri and R ₂ are independently selected from hydrogen or (Ci-Ci ₂)-alkyl, or R- _\ and R ₂ can optionally form an unsubstituted or substituted (C ₃-C ₇) cycloalkyi ring;

R ₃ is hydrogen or (Ci-Ci ₂)-alkyl; and B and A are as defined in the twelfth aspect, with the proviso that A is not a methyl group.

In another embodiment of the twelfth aspect, Z is

indicates the point of attachment;

m is 0 or 1 ;

Ri and R ₂ are independently selected from hydrogen or (Ci-Ci ₂)-alkyl, or R- _\ and R ₂ can optionally form an unsubstituted or substituted (C ₃-C ₇) cycloalkyi ring; R ₅ is selected from hydrogen, (CrCi ₂)-alkyl, CF ₃, (C ₃-C ₇)-cycloalkyl, aryl, or heterocyclyl; and B and A are as defined in the twelfth aspect,

with the proviso that A is not a methyl group.

In another embodiment of the twelfth as ect, Z is

indicates the point of attachment;

R ₅ is selected from hydrogen, (CrCi ₂)-alkyl, CF ₃, (C ₃-C ₇)-cycloalkyl, aryl, and heterocyclyl; and B and A are as defined in the twelfth aspect,

with the proviso that A is not a methyl group.

In another embodiment of the twelfth as ect, Z is

indicates the point of attachment;

m is 0 or 1 ;

Ri and R ₂ are independently selected from hydrogen or (CrCi ₂)-alkyl, or R- _\ and R ₂ can optionally form an unsubstituted or substituted (C ₃-C ₇) cycloalkyl ring;

R ₃ is hydrogen or (Ci-Ci ₂)-alkyl; and B and A are as defined in the twelfth aspect, with the proviso that A is not a methyl group.

In a thirteenth aspect, the present invention provides compounds of formula 1 represented by compounds of formula 1 c; wherein,

B is

wherein 1 and 2 are the points of attac ment of B to phenyl and to Z respectively;

Z is selected from:

indicates the point of attachment;

n is an integer selected from 1 -5;

m is 0 or 1 ;

Ri and R ₂ are independently selected from hydrogen or (CrCi ₂)-alkyl, or and R ₂ can optionally form an unsubstituted or substituted (C ₃-C ₇) cycloalkyl ring;

R ₃ is hydrogen or (CrCi ₂)-alkyl;

R ₅ is selected from hydrogen, (CrCi ₂)-alkyl, CF ₃, (C ₃-C ₇)-cycloalkyl, aryl, or heterocyclyl; and

A is selected from (Ci-Ci ₂)-alkyl, (C ₃-Ci ₂)-cycloalkyl, aryl or heterocyclyl; wherein,

(Ci-Ci ₂)-alkyl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (Ci-Ci ₂)-alkoxy, cyano, (C ₃-Ci ₂)-cycloalkyl, aryl or heterocyclyl;

(C ₃-Ci ₂)-cycloalkyl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (Ci-Ci ₂)-alkoxy, cyano, aryl or heterocyclyl;

aryl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (Ci-Ci ₂)-alkoxy, cyano, (Ci-Ci ₂)-alkyl, OCF ₃, CF ₃, (C ₃-Ci ₂)-cycloalkyl, aryl, aryloxy, heterocyclyl or O-heterocyclyl; or aryl may be fused with an unsubstituted or substituted 5 or 6-membered cycloalkyi ring optionally containing one or more heteroatoms selected from O, N or S;

heterocyclyl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (CrCi ₂)-alkoxy, cyano, (CrCi ₂)-alkyl, (C ₃-Ci ₂)-cycloalkyl, aryl, aryloxy, heterocyclyl or O-heterocyclyl;

with the proviso that A is not a methyl group.

In a fourteenth aspect, the present invention provides compounds of formula 1 represented by compounds of formula 1 c; wherein,

B is

wherein 1 and 2 are the points of attachment of B to phenyl and to Z respectively;

Z is selected from:

indicates the point of attachment;

n is an integer selected from 1 -5;

m is 0 or 1 : Ri and R ₂ are independently selected from hydrogen or (CrCi ₂)-alkyl, or R- _\ and R ₂ can optionally form an unsubstituted or substituted (C ₃-C ₇) cycloalkyi ring;

R ₃ is hydrogen or (CrCi ₂)-alkyl;

R ₅ is selected from hydrogen, (CrCi ₂)-alkyl, CF ₃, (C ₃-C ₇)-cycloalkyl, aryl, and heterocyclyl; and

A is selected from (Ci-Ci ₂)-alkyl, (C ₃-Ci ₂)-cycloalkyl, aryl or heterocyclyl; wherein,

(Ci-Ci ₂)-alkyl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (Ci-Ci ₂)-alkoxy, cyano, (C ₃-Ci ₂)-cycloalkyl, aryl or heterocyclyl;

(C ₃-Ci ₂)-cycloalkyl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (Ci-Ci ₂)-alkoxy, cyano, aryl or heterocyclyl;

aryl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (Ci-Ci ₂)-alkoxy, cyano, (Ci-Ci ₂)-alkyl, OCF ₃, CF ₃, (C ₃-Ci ₂)-cycloalkyl, aryl, aryloxy, heterocyclyl or O-heterocyclyl, or aryl may be fused with an unsubstituted or substituted 5 or 6-membered cycloalkyi ring optionally containing heteroatoms selected from O, N or S;

heterocyclyl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (Ci-Ci ₂)-alkoxy, cyano, (Ci-Ci ₂)-alkyl, (C ₃-Ci ₂)-cycloalkyl, aryl, aryloxy, heterocyclyl or O-heterocyclyl;

with the proviso that A is not a methyl group.

In a fifteenth aspect, the present invention provides compounds of formula 1 c; wherein,

B is

wherein 1 and 2 are the points of attachment of B to phenyl and to Z respectively;

Z is selected from:

indicates the point of attachment;

n is an integer selected from 1 -5;

m is 0 or 1 ;

Ri and R ₂ are independently selected from hydrogen or (CrCi ₂)-alkyl, or and R ₂ can optionally form an unsubstituted or substituted (C ₃-C ₇) cycloalkyl ring;

R ₃ is hydrogen or (CrCi ₂)-alkyl;

R ₅ is selected from hydrogen, (CrCi ₂)-alkyl, CF ₃, (C ₃-C ₇)-cycloalkyl, aryl, and heterocyclyl; and

A is selected from (Ci-Ci ₂)-alkyl, (C ₃-Ci ₂)-cycloalkyl, aryl or heterocyclyl; wherein,

(Ci-Ci ₂)-alkyl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (Ci-Ci ₂)-alkoxy, cyano, (C ₃-Ci ₂)-cycloalkyl, aryl or heterocyclyl;

(C ₃-Ci ₂)-cycloalkyl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (Ci-Ci ₂)-alkoxy, cyano, aryl or heterocyclyl;

aryl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (Ci-Ci ₂)-alkoxy, cyano, (Ci-Ci ₂)-alkyl, OCF ₃, CF ₃, (C ₃-Ci ₂)-cycloalkyl, aryl, aryloxy, heterocyclyl or O-heterocyclyl, or aryl may be fused with an unsubstituted or substituted 5 or 6-membered cycloalkyi ring optionally containing heteroatoms selected from O, N or S;

heterocyclyl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (CrCi ₂)-alkoxy, cyano, (CrCi ₂)-alkyl, (C ₃-Ci ₂)-cycloalkyl, aryl, aryloxy, heterocyclyl or O-heterocyclyl;

with the proviso that A is not a methyl group.

In a sixteenth aspect, the present invention provides compounds of formula 1 represented by compounds of

Formula 1 d

in all their stereoisomeric and tautomeric forms; and their pharmaceutically acceptable salts, solvates, polymorphs, prodrugs, carboxylic acid isosteres and N-oxides;

wherein,

Z is selected from:

indicates the point of attachment; n is an integer selected from 1 -5;

m is 0 or 1 ;

Ri and R ₂ are independently selected from hydrogen or (CrCi ₂)-alkyl, or and R ₂ can optionally form an unsubstituted or substituted (C ₃-C ₇) cycloalkyl ring;

R ₃ is hydrogen or (CrCi ₂)-alkyl;

R ₅ is selected from hydrogen, (CrCi ₂)-alkyl, CF ₃, (C ₃-C ₇)-cycloalkyl, aryl, and heterocyclyl;

B is a 5-membered heteroaryl ring represented by any one of the general structures (i) to (x);

wherein 1 and 2 are the points of attachment of B to phenyl and to Z respectively and R ₅ is selected from hydrogen, (Ci-Ci ₂)-alkyl or aryl; or B is a 6-membered heteroaryl ring containing 1 or 2 N-atoms, wherein the 6-membered heteroaryl ring may be unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (Ci-Ci ₂)-alkoxy, cyano, nitro, (Ci-Ci ₂)-alkyl, (C ₂-Ci ₂)-alkenyl, (C ₂-Ci ₂)-alkynyl, (C ₃-Ci ₂)- cycloalkyl, aryl, aryloxy, heterocyclyl and O-heterocyclyl; and

A is selected from (Ci-Ci ₂)-alkyl, (C ₃-Ci ₂)-cycloalkyl, aryl or heterocyclyl; wherein,

(Ci-Ci ₂)-alkyl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (Ci-Ci ₂)-alkoxy, cyano, (C ₃-Ci ₂)-cycloalkyl, aryl or heterocyclyl;

(C ₃-Ci ₂)-cycloalkyl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (Ci-Ci ₂)-alkoxy, cyano, aryl or heterocyclyl;

aryl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (Ci-Ci ₂)-alkoxy, cyano, (Ci-Ci ₂)-alkyl, OCF ₃, CF ₃, (C ₃-Ci ₂)-cycloalkyl, aryl, aryloxy, heterocyclyl or O-heterocyclyl, or aryl may be fused with an unsubstituted or substituted 5 or 6-membered cycloalkyi ring optionally containing heteroatoms selected from O, N or S;

heterocyclyl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (CrCi ₂)-alkoxy, cyano, (CrCi ₂)-alkyl, (C ₃-Ci ₂)-cycloalkyl, aryl, aryloxy, heterocyclyl or O-heterocyclyl;

with the proviso that A is not a methyl group.

In a seventeenth aspect, the present invention provides compounds of formula 1 represented by compounds

Formula 1 e

in all their stereoisomeric and tautomeric forms; and their pharmaceutically acceptable salts, solvates, polymorphs, prodrugs, carboxylic acid isosteres and N-oxides;

wherein,

Z is selected from:

indicates the point of attachment;

n is an integer selected from 1 -5;

m is 0 or 1 ; Ri and R ₂ are independently selected from hydrogen or (CrCi ₂)-alkyl, or R- _\ and R ₂ can optionally form an unsubstituted or substituted (C ₃-C ₇) cycloalkyl ring;

R ₃ is hydrogen or (CrCi ₂)-alkyl;

R ₅ is selected from hydrogen, (CrCi ₂)-alkyl, CF ₃, (C ₃-C ₇)-cycloalkyl, aryl, or heterocyclyl;

B is a 5-membered heteroaryl ring represented by any one of the general structures (i) to (x);

R ₆ is selected from hydrogen, methyl, cyano or nitro; and

A is selected from (Ci-Ci ₂)-alkyl, (C ₃-Ci ₂)-cycloalkyl, aryl or heterocyclyl; wherein,

(Ci-Ci ₂)-alkyl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (Ci-Ci ₂)-alkoxy, cyano, (C ₃-Ci ₂)-cycloalkyl, aryl or heterocyclyl;

(C ₃-Ci ₂)-cycloalkyl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (Ci-Ci ₂)-alkoxy, cyano, aryl or heterocyclyl;

aryl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (Ci-Ci ₂)-alkoxy, cyano, (Ci-Ci ₂)-alkyl, OCF ₃, CF ₃, (C ₃-Ci ₂)-cycloalkyl, aryl, aryloxy, heterocyclyl or O-heterocyclyl, or aryl may be fused with an unsubstituted or substituted 5 or 6-membered cycloalkyi ring optionally containing heteroatoms selected from O, N or S;

heterocyclyl is unsubstituted or substituted with one or more groups selected from halogen, hydroxy, (CrCi ₂)-alkoxy, cyano, (CrCi ₂)-alkyl, (C ₃-Ci ₂)-cycloalkyl, aryl, aryloxy, heterocyclyl or O-heterocyclyl;

with the proviso that A is not a methyl group.

In an eighteenth aspect, the present invention provides compounds of formula 1 , wherein in all the above aspects and/or embodiments A is an unsubstituted aryl or an aryl substituted with one or more groups selected from halogen, hydroxy, (C ₁-C ₁₂)- alkoxy, cyano, unsubstituted or substituted (Ci-Ci ₂)-alkyl, OCF ₃, CF ₃, unsubstituted or substituted (C ₃-Ci ₂)-cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted aryloxy, unsubstituted or substituted heterocyclyl, or O-heterocyclyl. In a nineteenth aspect, the present invention provides compounds of formula 1 , wherein in all the above aspects and/or embodiments A is an aryl group which may be fused with an unsubstituted or substituted 5 or 6-membered cycloalkyi ring optionally containing one or more heteroatoms selected from O, N or S. In a twentieth aspect, the present invention provides compounds of formula 1 , wherein in all the above aspects and/or embodiments A is an unsubstituted heterocyclyl or a heterocyclyl substituted with one or more groups selected from halogen, hydroxy, (Ci-Ci ₂)-alkoxy, cyano, unsubstituted or substituted (Ci-Ci ₂)-alkyl, unsubstituted or substituted (C ₃-Ci ₂)-cycloalkyl, unsubstituted or substituted aryl, unsubstituted or substituted aryloxy, heterocyclyl or O-heterocyclyl.

In a twenty first aspect, the present invention provides compounds of formula 1 , wherein in all the above aspects and/or embodiments A is an unsubstituted (C ₃-Ci ₂)- cycloalkyl or (C ₃-Ci ₂)-cycloalkyl substituted with one or more groups selected from halogen, hydroxy, unsubstituted or substituted (Ci-Ci ₂)-alkyl, (Ci-Ci ₂)-alkoxy, cyano, nitro, unsubstituted or substituted aryl, or unsubstituted or substituted heterocyclyl.

In a twenty second aspect, the present invention provides compounds of formula 1 , wherein in all the above aspects and/or embodiments A is an unsubstituted (C Ci ₂)- alkyl or (CrCi ₂)-alkyl substituted with one or more groups selected from halogen, hydroxy, (CrCi ₂)-alkoxy, cyano, unsubstituted or substituted (C ₃-Ci ₂)-cycloalkyl, unsubstituted or substituted aryl, or unsubstituted or substituted heterocyclyl; with the proviso that A is not a methyl group.

In an aspect, the present invention provides compounds of formula 1 , wherein m is 0.

In another aspect, the present invention provides compounds of formula 1 , wherein m is 1.

In an aspect, the present invention provides compounds of formula 1 , wherein n is 1 .

In another aspect, the present invention provides compounds of formula 1 , wherein n is 2.

In yet another aspect, the present invention provides compounds of formula 1 , wherein n is 3.

In a further aspect, the present invention provides compounds of formula 1 , wherein n is 4.

In a still further aspect, the present invention provides compounds of formula 1 , wherein n is 5.

In an aspect, the present invention provides compounds of formula 1 , wherein Ri and R ₂ are methyl groups.

In another aspect, the present invention provides compounds of formula 1 , wherein R ₃ is hydrogen.

In yet another aspect, the present invention provides compounds of formula 1 , wherein R ₃ is unsubstituted or substituted alkyl. In another aspect, the present invention provides compounds of formula D: wherein B and Z are as defined in formula 1 of the first aspect of the invention; for use as intermediates in the preparation of the compounds of formula 1 .

In one aspect, the present invention provides a process for the preparation of the compound of formula 1 represented by the compound of formula 1 a:

Formula 1 a

wherein A, B and Z are as defined in formula 1 ;

the steps comprising:

Step a) treating the compound of formula D:

wherein B and Z are as defined in formula 1 of any one of the aspects of the invention; with a compound of formula 8 (i):

A-N=C=0

8 (i)

wherein A is as defined in formula 1 of any one of the aspects of the invention;

in a solvent selected from THF or dichloromethane at room temperature for 2-16 h; or alternately, treating the comp

with the compound of formula 8 (ii):

A-NH ₂

8 (ii)

wherein A is as defined in formula 1 of any one of the aspects of the invention;

in presence of a coupling agent, carbonyl diimidazole in a suitable solvent such as THF at room temperature for about 24 h; and

Step b) hydrolysis of compounds of formula 1 a;

wherein Z is:

R ₃ is (Ci-Ci ₂)-alkyl;

by reaction with a suitable reagent such as aqueous LiOH in a suitable solvent such as THF or methanol or a mixture thereof, at room temperature for 2-16 h into the corresponding carboxylic acids of formula 1 a (R ₃ is H); and conversion of the carboxylic acids obtained into their corresponding pharmaceutically acceptable salts or optionally into their corresponding ester prodrugs.

The compound 8(i) used in step (a) of the above process is a commercially available compound (e.g. phenyl isocyanate).

In another aspect, the present invention provides a process for the preparation of the compound of formula 1 represented by the compound of formula 1 b:

Formula 1 b

wherein A, B and Z are as defined in formula 1 of of any one of the aspects of the invention;

the steps comprising:

Step a) treating the compound of formula D:

wherein B and Z are as defined in formula 1 ;with compound of formula 8 (iii):

A-N=C=S

8 (iii)

wherein A is as defined in formula 1 of any one of the aspects of the invention;

in a suitable solvent such as THF or dichloromethane at room temperature for 2-16 h; and

Step b) hydrolysis of compounds of formula 1 b;

wherein Z is:

R ₃ is (Ci-Ci ₂)-alkyl;

by reaction with a suitable reagent such as aqueous LiOH in a suitable solvent such as THF or methanol or a mixture thereof, at room temperature for 2-16 h into the corresponding carboxylic acids of formula 1 b (R ₃ is H); and conversion of the carboxylic acids obtained into their corresponding pharmaceutically acceptable salts or optionally into their corresponding ester prodrugs.

In a further aspect, the present invention provides a process for the preparation of the compound of formula 1 represented by the compound of formula 1 c:

Formula 1 c

wherein A, B and Z are as defined in formula 1 of of any one of the aspects of the invention;

the steps comprising:

Step a) treating the compound of formula D:

wherein B and Z are as defined in formula 1 ;with commercially available compound of formula 8 (iv):

A-C(0)-Cl

8 (iv)

wherein A is as defined in formula 1 of any one of the aspects of the invention;

in a suitable solvent such as dichloromethane or chloroform in a suitable base such as pyridine at room temperature for 1 -2 h;

or alternately, by reacting compound of formula D:

with commercially available compound of formula 8 (v):

A-COOR ₃

8(v)

wherein A and R ₃ are as defined in formula 1 of any one of the aspects of the invention; in a suitable solvent such as toluene and a coupling agent such as trimethylaluminium; and

Step b) hydrolysis of compounds of formula 1 c;

wherein Z is:

R ₃ is (Ci-Ci ₂)-alkyl;

by reaction with a suitable reagent such as aqueous LiOH in a suitable solvent such as THF or methanol or a mixture thereof, at room temperature for 2-16 h into the corresponding carboxylic acids of formula 1 c (R ₃ is H); and conversion of the carboxylic acids obtained into their corresponding pharmaceutically acceptable salts or optionally into their corresponding ester prodrugs.

In a still further aspect, the present invention provides a process for the preparation of the compound of formula 1 represented by the compound of formula 1 d:

Formula 1 d

wherein A, B and Z are as defined in formula 1 of any one of the aspects of the invention;

the steps comprising:

Step a) treating the compound of formula D:

wherein B and Z are as defined in formula 1 of any one of the aspects of the invention; with compound of formula 8 (vi):

A-SOs-CI

8 (vi)

wherein A is as defined in formula 1 ;

in a suitable solvent such as dichloromethane or chloroform in a suitable base such as pyridine at room temperature for 1 -2 h; and

Step b) hydrolysis of compounds of formula 1 d;

wherein Z is:

R ₃ is (Ci-Ci ₂)-alkyl;

by reaction with a suitable reagent such as aqueous LiOH in a suitable solvent such as THF or methanol or a mixture thereof, at room temperature for 2-16 h into the corresponding carboxylic acids of formula 1 d (R ₃ is H); and conversion of the carboxylic acids obtained into their corresponding pharmaceutically acceptable salts or optionally into their corresponding ester prodrugs.

In a still further aspect, the present invention provides a process for the preparation of the compound of formula 1 represented by the compound of formula 1 e:

Formula 1 e

wherein A, B, Z and R ₆ are as defined in formula 1 of any one of the aspects of the invention;

the steps comprising:

Step a) reacting the compound of formula 1 b:

Formula 1 b

with the compound of formula 8 (vii):

R ₆-NH ₂

8 (vii)

wherein R ₆ is as defined in formula 1 according to any one of the aspects of the invention;

in presence of HgO in a suitable solvent such as methanol at room temperature for 1 -3 h; and

Step b) hydrolysis of compounds of formula 1 e;

wherein Z is:

R ₃ is (Ci-Ci ₂)-alkyl;

by reaction with a suitable reagent such as aqueous LiOH in a suitable solvent such as THF or methanol or a mixture thereof, at room temperature for 2-16 h into the corresponding carboxylic acids of formula 1 e (R ₃ is H); and conversion of the carboxylic acids obtained into their corresponding pharmaceutically acceptable salts or optionally into their corresponding ester prodrugs.

In an aspect, the present invention provides compounds of formula 1 selected from:

Methyl 3-(5-(4-(3-(3-(trifluoromethyl)phenyl)ureido)phenyl)thiazol- 2-yl) propanoate;

3-(5-(4-(3-(3-(Trifluoromethyl)phenyl)ureido)phenyl)thiaz ol-2-yl)propanoic acid;

Methyl 3-(5-(4-(3-(2-chlorophenyl)ureido)phenyl)thiazol-2-yl)propan oate;

3-(5-(4-(3-(2-Chlorophenyl)ureido)phenyl)thiazol-2-yl)propan oic acid;

Methyl 3-(5-(4-(3-cyclohexylureido)phenyl)thiazol-2-yl)propanoate;

3-(5-(4-(3-Cyclohexylureido)phenyl)thiazol-2-yl)propanoic acid;

Methyl 3-(5-(4-(3-(4-chloro-2-phenoxyphenyl)ureido)phenyl)thiazol-2 -yl) propanoate; 3-(5-(4-(3-(4-Chloro-2-phenoxyphenyl)ureido)phenyl)thiazol-2 -yl)propanoic acid;

Methyl 3-(5-(4-(4-t-butylbenzamido)phenyl)thiazol-2-yl)propanoate;

3-(5-(4-(4-t-butylbenzamido)phenyl)thiazol-2-yl)propanoic acid;

Methyl 3-(5-(4-(4-pentylbenzamido)phenyl)thiazol-2-yl)propanoate;

3-(5-(4-(4-Pentylbenzamido)phenyl)thiazol-2-yl)propanoic acid;

Methyl 3-(5-(4-(3-ethoxy-5-(methoxymethyl)benzamido)phenyl)thiazol- 2-yl) propanoate;

3-(5-(4-(3-Ethoxy-5-(methoxymethyl)benzamido)phenyl)thiaz ol-2-yl)propanoic acid;

Methyl 3-(5-(4-(4-pentylbenzamido)phenyl)thiazol-2-yl)propanoate;

3-(5-(4-(2-Naphthamido)phenyl)thiazol-2-yl)propanoic acid;

Methyl 3-(5-(4-(4-butoxybenzamido)phenyl)thiazol-2-yl)propanoate;

3-(5-(4-(4-Butoxybenzamido)phenyl)thiazol-2-yl)propanoic acid;

Methyl 3-(5-(4-(2,4-dimethoxyphenylsulfonamido)phenyl)thiazol-2-yl) propanoate;

3-(5-(4-(2,4-Dimethoxyphenylsulfonamido)phenyl)thiazol-2-yl) propanoic acid;

Methyl 3-(5-(4-(3-(2-chlorophenyl)ureido)phenyl)thiazol-2-yl)-2,2-d imethyl propanoate;

3-(5-(4-(3-(2-Chlorophenyl)ureido)phenyl)thiazol-2-yl)-2, 2-dimethylpropanoic acid;

Methyl 2,2-dimethyl-3-(5-(4-(3-(4-(trifluoromethyl)phenyl)ureido)ph enyl) thiazol -2- yl)propanoate;

2,2-Dimethyl-3-(5-(4-(3-(4-(trifluoromethyl)phenyl)ureido)ph enyl)thiazol-2-yl) propanoic acid;

Methyl 2,2-dimethyl-3-(5-(4-(3-(4-(trifluoromethyl)phenyl)ureido)ph enyl) thiazol-2- yl)propanoate;

3-(5-(4-(3-(4-Fluorophenyl)ureido)phenyl)thiazol-2-yl)-2,2-d imethylpropanoic acid; Methyl 3-(5-(4-(3-(4-methoxyphenyl)ureido)phenyl)thiazol-2-yl)-2,2- dimethyl propanoate;

3-(5-(4-(3-(4-Methoxyphenyl)ureido)phenyl)thiazol-2-yl)-2,2- dimethyl propanoic acid; Methyl 3-(5-(4-(3-cyclohexylureido)phenyl)thiazol-2-yl)-2,2-dimethy l propanoate;

3-(5-(4-(3-Cyclohexylureido)phenyl)thiazol-2-yl)-2,2-dime thylpropanoic acid;

Methyl 3-(5-(4-(3-(4-chloro-2-phenoxyphenyl)ureido)phenyl)thiazol-2 -yl)-2,2- dimethylpropanoate;

3-(5-(4-(3-(4-Chloro-2-phenoxyphenyl)ureido)phenyl)thiazol-2 -yl)-2,2-dimethylpropanoic acid;

Methyl 3-(5-(4-(4-tert-butylbenzamido)phenyl)thiazol-2-yl)-2,2-dime thyl propanoate;

3-(5-(4-(4-t-Butylbenzamido)phenyl)thiazol-2-yl)-2,2-dime thylpropanoic acid;

Methyl 3-(5-(4-biphenyl-4-ylcarboxamidophenyl)thiazol-2-yl)-2,2-dim ethyl propanoate; 3- (5-(4-Biphenyl-4-ylcarboxamidophenyl)thiazol-2-yl)-2,2-dimet hylpropanoic acid; Methyl 4-(5-(4-(3-(3-(trifluoromethyl)phenyl)ureido)phenyl)thiazol- 2-yl) butanoate;

4- (5-(4-(3-(3-(Trifluoromethyl)phenyl)ureido)phenyl)thiazol-2- yl)butanoic acid;

Methyl 4-(5-(4-(3-(2-chlorophenyl)ureido)phenyl)thiazol-2-yl)butano ate;

4-(5-(4-(3-(2-Chlorophenyl)ureido)phenyl)thiazol-2-yl)but anoic acid;

Methyl 4-(5-(4-(3-(3,4-dimethylphenyl)ureido)phenyl)thiazol-2-yl)bu tanoate;

4-(5-(4-(3-(3,4-Dimethylphenyl)ureido)phenyl)thiazol-2-yl)bu tanoic acid;

Methyl 4-(5-(4-(3-(4-chloro-2-phenoxyphenyl)ureido)phenyl)thiazol-2 -yl) butanoate;

4-(5-(4-(3-(4-Chloro-2-phenoxyphenyl)ureido)phenyl)thiazo l-2-yl)butanoic acid;

Methyl 4-(5-(4-(4-t-butylbenzamido)phenyl)thiazol-2-yl)butanoate;

4-(5-(4-(4-t-Butylbenzamido)phenyl)thiazol-2-yl)butanoic acid;

Methyl 4-(5-(4-(4-pentylbenzamido)phenyl)thiazol-2-yl)butanoate;

4-(5-(4-(4-Pentylbenzamido)phenyl)thiazol-2-yl)butanoic acid;

Methyl 4-(5-(4-biphenyl-4-ylcarboxamidophenyl)thiazol-2-yl)butanoat e;

4-(5-(4-Biphenyl-4-ylcarboxamidophenyl)thiazol-2-yl)butanoic acid;

Methyl 4-(5-(4-(2,4-dimethoxyphenylsulfonamido)phenyl)thiazol-2-yl) butanoate;

4-(5-(4-(2,4-Dimethoxyphenylsulfonamido)phenyl)thiazol-2-yl) butanoic acid;

Methyl 3,3-dimethyl-4-(5-(4-(3-(3-(trifluoromethyl)phenyl)ureido)ph enyl) thiazol-2- yl)butanoate;

3,3-Dimethyl-4-(5-(4-(3-(3-(trifluoromethyl)phenyl)ureido)ph enyl)thiazol-2-yl) butanoic acid;

Methyl 4-(5-(4-(3-(2-chlorophenyl)ureido)phenyl)thiazol-2-yl)-3,3-d imethyl butanoate; 4-(5-(4-(3-(2-Chlorophenyl)ureido)phenyl)thiazol-2-yl)-3,3-d imethylbutanoic acid; Methyl 4-(5-(4-(3-(4-chloro-2-phenoxyphenyl)ureido)phenyl)thiazol-2 -yl)-3,3- dimethylbutanoate;

4-(5-(4-(3-(4-Chloro-2-phenoxyphenyl)ureido)phenyl)thiazol-2 -yl)-3,3-dimethyl butanoic acid;

Methyl 4-(5-(4-(4-tert-butylbenzamido)phenyl)thiazol-2-yl)-3,3-dime thyl butanoate; 4-(5-(4-(4-t-Butylbenzamido)phenyl)thiazol-2-yl)-3,3-dimethy lbutanoic acid;

Methyl 4-(5-(4-biphenyl-4-ylcarboxamidophenyl)thiazol-2-yl)-3,3-dim ethyl butanoate; 4-(5-(4-Biphenyl-4-ylcarboxamidophenyl)thiazol-2-yl)-3,3-dim ethylbutanoic acid;

Methyl 3,3-dimethyl-4-(5-(4-(4-pentylbenzamido)phenyl)thiazol-2-yl) butanoate;

3,3-Dimethyl-4-(5-(4-(4-pentylbenzamido)phenyl)thiazol-2- yl)butanoic acid; Methyl 4-(5-(4-(2,4-dimethoxyphenylsulfonamido)phenyl)thiazol-2-yl) -3,3- dimethylbutanoate;

4-(5-(4-(2,4-Dimethoxyphenylsulfonamido)phenyl)thiazol-2-yl) -3,3-dimethylbutanoic acid;

Methyl 2,2-dimethyl-4-(5-(4-(3-(3-(trifluoromethyl)phenyl)ureido)ph enyl) thiazol-2- yl)butanoate;

2,2-Dimethyl-4-(5-(4-(3-(3-(trifluoromethyl)phenyl)ureido)ph enyl)thiazol-2-yl) butanoic acid;

Methyl 4-(5-(4-(3-(2-chlorophenyl)ureido)phenyl)thiazol-2-yl)-2,2-d imethyl butanoate; 4-(5-(4-(3-(2-Chlorophenyl)ureido)phenyl)thiazol-2-yl)-2,2-d imethylbutanoic acid;

Methyl 4-(5-(4-(3-(4-chloro-2-phenoxyphenyl)ureido)phenyl)thiazol-2 -yl)-2,2- dimethylbutanoate;

4-(5-(4-(3-(4-Chloro-2-phenoxyphenyl)ureido)phenyl)thiazol-2 -yl)-2,2-dimethylbutanoic acid;

Methyl 4-(5-(4-(3-cyclohexylureido)phenyl)thiazol-2-yl)-2,2-dimethy l butanoate;

4-(5-(4-(3-Cyclohexylureido)phenyl)thiazol-2-yl)-2,2-dime thylbutanoic acid;

Methyl 4-(5-(4-(3-(4-fluorophenyl)ureido)phenyl)thiazol-2-yl) y-2,2-dimethyl butanoate; 4-(5-(4-(3-(2-Chlorophenyl)ureido)phenyl)thiazol-2-yl)-2,2-d imethylbutanoic acid;

Methyl 4-(5-(4-(3-(4-methoxyphenyl)ureido)phenyl)thiazol-2-yl)-2,2- dimethyl butanoate; 4-(5-(4-(3-(4-Methoxyphenyl)ureido)phenyl)thiazol-2-yl)-2,2- dimethyl butanoic acid; Methyl 4-(5-(4-(3-(4-isopropylphenyl)ureido)phenyl)thiazol-2-yl)-2, 2-dimethyl butanoate; 4-(5-(4-(3-(4-lsopropylphenyl)ureido)phenyl)thiazol-2-yl)-2, 2-dimethyl butanoic acid; Methyl 4-(5-(4-(3-(2,4-difluorophenyl)ureido)phenyl)thiazol-2-yl)-2 ,2-dimethylbutanoate; 4-(5-(4-(3-(2,4-Difluorophenyl)ureido)phenyl)thiazol-2-yl)-2 ,2-dimethyl butanoic acid; Methyl 4-(5-(4-(3-(2-fluorophenyl)ureido)phenyl)thiazol-2-yl)-2,2-d imethyl butanoate; 4-(4-(4-(3-(2-Fluorophenyl)ureido)phenyl)-3H-pyrrol-2-yl)-2, 2-dimethyl butanoic acid; Methyl 4-(5-(4-(4-t-butylbenzamido)phenyl)thiazol-2-yl)-2,2-dimethy l butanoate;

4-(5-(4-(4-t-butylbenzamido)phenyl)thiazol-2-yl)-2,2-dime thylbutanoic acid;

Methyl 4-(5-(4-biphenyl-4-ylcarboxamidophenyl)thiazol-2-yl)-2,2-dim ethyl butanoate; 4-(5-(4-Biphenyl-4-ylcarboxamidophenyl)thiazol-2-yl)-2,2-dim ethylbutanoic acid;

Methyl 2,2-dimethyl-4-(5-(4-(4-(oxazol-5-yl)benzamido)phenyl)thiazo l-2-yl) butanoate; 2,2-Dimethyl-4-(5-(4-(4-(oxazol-5-yl)benzamido)phenyl)thiazo l-2-yl)butanoic acid;

Methyl 2,2-dimethyl-4-(5-(4-(4-phenylthiazole-2-carboxamido)phenyl) thiazol-2-yl) butanoate; 2,2-Dimethyl-4-(5-(4-(4-phenylthiazole-2-carboxamido)phenyl) thiazol-2-yl) butanoic acid;

Methyl 3-(5-(4-(3-(2-chlorophenyl)ureido)phenyl)oxazol-2-yl)-2,2-di methyl propanoate; 3-(5-(4-(3-(2-Chlorophenyl)ureido)phenyl)oxazol-2-yl)-2,2-di methylpropanoic acid; Methyl 2,2-dimethyl-3-(5-(4-(3-(4-(trifluoromethyl)phenyl)ureido)ph enyl) oxazol-2- yl)propanoate;

2,2-Dimethyl-3-(5-(4-(3-(4-(trifluoromethyl)phenyl)ureido)ph enyl)oxazol-2-yl) propanoic acid;

Methyl 3-(5-(4-(3-(4-fluorophenyl)ureido)phenyl)oxazol-2-yl)-2,2-di methyl propanoate; 3-(5-(4-(3-(4-Fluorophenyl)ureido)phenyl)oxazol-2-yl)-2,2-di methylpropanoic acid; Methyl 3-(5-(4-(3-(4-methoxyphenyl)ureido)phenyl)oxazol-2-yl)-2,2-d imethyl propanoate;

3-(5-(4-(3-(4-Methoxyphenyl)ureido)phenyl)oxazol-2-yl)-2,2-d imethyl propanoic acid; Methyl 3-(5-(4-(3-(4-chloro-2-phenoxyphenyl)ureido)phenyl)oxazol-2- yl)-2,2- dimethylpropanoate;

3-(5-(4-(3-(4-Chloro-2-phenoxyphenyl)ureido)phenyl)oxazol-2- yl)-2,2-dimethyl propanoic acid;

Methyl 3-(5-(4-(4-t-butylbenzamido)phenyl)oxazol-2-yl)-2,2-dimethyl propanoate;

3-(5-(4-(4-t-Butylbenzamido)phenyl)oxazol-2-yl)-2,2-dimet hylpropanoic acid;

Methyl 3-(5-(4-biphenyl-4-ylcarboxamidophenyl)oxazol-2-yl)-2,2-dime thyl propanoate;

3- (5-(4-Biphenyl-4-ylcarboxamidophenyl)oxazol-2-yl)-2,2-dimeth ylpropanoic acid; Methyl 4-(5-(4-(3-(3-(trifluoromethyl)phenyl)ureido)phenyl)thiazol- 2-yl)

cyclohexanecarboxylate;

4- (5-(4-(3-(3-(Trifluoromethyl)phenyl)ureido)phenyl)thiazol-2- yl)cyclohexane carboxylic acid;

Methyl 4-(5-(4-(3-p-tolylureido)phenyl)thiazol-2-yl)cyclohexanecarb oxylate;

4-(5-(4-(3-p-Tolylureido)phenyl)thiazol-2-yl)cyclohexanec arboxylic acid;

Methyl 4-(5-(4-(3-(2,4-difluorophenyl)ureido)phenyl)thiazol-2yl)cyc lohexane carboxylate;

4-(5-(4-(3-(2,4-Difluorophenyl)ureido)phenyl)thiazol-2-yl)cy clohexane carboxylic acid; Methyl 4-(5-(4-(3-(2-fluorophenyl)ureido)phenyl)thiazol-2-yl)cycloh exane carboxylate; 4-(5-(4-(3-(2-Fluorophenyl)ureido)phenyl)thiazol-2-yl)cycloh exanecarboxylic acid; Methyl 4-(5-(4-(3-cyclohexylureido)phenyl)thiazol-2-yl)cyclohexane carboxylate;

4-(5-(4-(3-Cyclohexylureido)phenyl)thiazol-2-yl)cyclohexa necarboxylic acid; Methyl 4-(5-(4-(3-(3-chlorophenyl)ureido)phenyl)thiazol-2-yl)cycloh exane carboxylate; 4-(5-(4-(3-(3-Chlorophenyl)ureido)phenyl)thiazol-2-yl)cycloh exanecarboxylic acid; Methyl 4-(5-(4-(3-(4-chlorophenyl)ureido)phenyl)thiazol-2-yl)cycloh exane carboxylate; 4-(5-(4-(3-(4-Chlorophenyl)ureido)phenyl)thiazol-2-yl)cycloh exanecarboxylic acid; Methyl 4-(5-(4-(3-(2-chloro-4-(trifluoromethyl)phenyl)ureido)phenyl )thiazol-2-yl) cyclohexanecarboxylate;

4-(5-(4-(3-(2-Chloro-4-(trifluoromethyl)phenyl)ureido)phenyl )thiazol-2-yl)

cyclohexanecarboxylic acid;

Methyl 4-(5-(4-(3-(2-chloro-5-methylphenyl)ureido)phenyl)thiazol-2- yl) cyclo hexanecarboxylate;

4-(5-(4-(3-(2-Chloro-5-methylphenyl)ureido)phenyl)thiazol-2- yl)cyclohexane carboxylic acid;

Methyl 4-(5-(4-(3-(3-chloro-2-fluorophenyl)ureido)phenyl)thiazol-2- yl)cyclo

hexanecarboxylate;

4-(5-(4-(3-(3-Chloro-2-fluorophenyl)ureido)phenyl)thiazol-2- yl)cyclohexane carboxylic acid;

Methyl 4-(5-(4-(3-(4-methoxy-2-methylphenyl)ureido)phenyl)thiazol-2 -yl)

cyclohexanecarboxylate;

4-(5-(4-(3-(4-Methoxy-2-methylphenyl)ureido)phenyl)thiazol-2 -yl)cyclo

hexanecarboxylic acid;

Methyl 4-(5-(4-(3-benzo[d][1 ,3]dioxol-5-ylureido)phenyl)thiazol-2-yl)cyclo

hexanecarboxylate;

4-(5-(4-(3-Benzo[d][1 ,3]dioxol-5-ylureido)phenyl)thiazol-2-yl)cyclohexane carboxylic acid;

Methyl 4-(5-(4-(3-(2-chloro-6-(trifluoromethyl)phenyl)ureido)phenyl )thiazol-2- yl)cyclohexanecarboxylate;

4-(5-(4-(3-(2-Chloro-6-(trifluoromethyl)phenyl)ureido)phenyl )thiazol-2-yl)

cyclohexanecarboxylic acid;

Methyl 4-(5-(4-(3-(4-chloro-2-(trifluoromethyl)phenyl)ureido)phenyl )thiazol-2- yl)cyclohexanecarboxylate;

4-(5-(4-(3-(4-Chloro-2-(trifluoromethyl)phenyl)ureido)phenyl )thiazol-2-yl)

cyclohexanecarboxylic acid;

Methyl 4-(5-(4-(3-(2-chloro-6-methylphenyl)ureido)phenyl)thiazol-2- yl) cyclo hexanecarboxylate; 4-(5-(4-(3-(2-Chloro-6-methylphenyl)ureido)phenyl)thiazol-2- yl)cyclohexane carboxylic acid;

Methyl 4-(5-(4-(3-(5-chloro-2-methylphenyl)ureido)phenyl)thiazol-2- yl) cyclo hexanecarboxylate;

4-(5-(4-(3-(5-Chloro-2-methylphenyl)ureido)phenyl)thiazol-2- yl)cyclohexane carboxylic acid;

Methyl 4-(5-(4-(3-(2-(trifluoromethyl)phenyl)ureido)phenyl)thiazol- 2-yl)cyclo hexanecarboxylate;

4-(5-(4-(3-(2-(Trifluoromethyl)phenyl)ureido)phenyl)thiazol- 2-yl)cyclohexane carboxylic acid;

Methyl 4-(5-(4-(3-(2-(trifluoromethoxy)phenyl)ureido)phenyl)thiazol -2-yl)

cyclohexanecarboxylate;

4-(5-(4-(3-(2-(Trifluoromethoxy)phenyl)ureido)phenyl)thiazol -2-yl)cyclohexane carboxylic acid;

Methyl 4-(5-(4-(3-(4-phenoxyphenyl)ureido)phenyl)thiazol-2-yl)cyclo hexane carboxylate;

4-(5-(4-(3-(4-Phenoxyphenyl)ureido)phenyl)thiazol-2-yl)cyclo hexane carboxylic acid; Methyl 4-(5-(4-(3-(4-chloro-2-fluorophenyl)ureido)phenyl)thiazol-2- yl)cyclo

hexanecarboxylate;

4-(5-(4-(3-(4-Chloro-2-fluorophenyl)ureido)phenyl)thiazol-2- yl)cyclohexane carboxylic acid;

Methyl 4-(5-(4-(3-(2-fluoro-5-methylphenyl)ureido)phenyl)thiazol-2- yl)cyclo

hexanecarboxylate;

4-(5-(4-(3-(2-Fluoro-5-methylphenyl)ureido)phenyl)thiazol-2- yl)cyclohexane carboxylic acid;

Methyl 4-(5-(4-(3-(2-fluoro-6-(trifluoromethyl)phenyl)ureido)phenyl )thiazol-2- yl)cyclohexanecarboxylate;

4-(5-(4-(3-(2-Fluoro-6-(trifluoromethyl)phenyl)ureido)phenyl )thiazol-2-yl)

cyclohexanecarboxylic acid;

Methyl 4-(5-(4-(3-(3-fluorophenyl)ureido)phenyl)thiazol-2-yl)cycloh exane carboxylate; 4-(5-(4-(3-(3-Fluorophenyl)ureido)phenyl)thiazol-2-yl)cycloh exanecarboxylic acid; Methyl 4-(5-(4-(3-(3,4-difluorophenyl)ureido)phenyl)thiazol-2-yl)cy clohexane carboxylate;

4-(5-(4-(3-(3,4-Difluorophenyl)ureido)phenyl)thiazol-2-yl)cy clohexane carboxylic acid; Methyl 4-(5-(4-(3-(3,5-difluorophenyl)ureido)phenyl)thiazol-2-yl)cy clohexane

carboxylate;

4-(5-(4-(3-(3,5-Difluorophenyl)ureido)phenyl)thiazol-2-yl)cy clohexane carboxylic acid; Methyl 4-(5-(4-(3-(2,6-difluorophenyl)ureido)phenyl)thiazol-2-yl)cy clohexane

carboxylate;

4-(5-(4-(3-(2,6-Difluorophenyl)ureido)phenyl)thiazol-2-yl)cy clohexane carboxylic acid; Methyl 4-(5-(4-(3-(2,3,4-trifluorophenyl)ureido)phenyl)thiazol-2-yl )cyclo

hexanecarboxylate;

4-(5-(4-(3-(2,3,4-Trifluorophenyl)ureido)phenyl)thiazol-2-yl )cyclohexane carboxylic acid; Methyl 4-(5-(4-(3-(2-chlorophenyl)ureido)phenyl)thiazol-2-yl)cycloh exane carboxylate; 4-(5-(4-(3-(2-Chlorophenyl)ureido)phenyl)thiazol-2-yl)cycloh exanecarboxylic

acid;

Methyl 4-(5-(4-(3-(4-chloro-2-phenoxyphenyl)ureido)phenyl)thiazol-2 -yl)

cyclohexanecarboxylate;

4-(5-(4-(3-(4-Chloro-2-phenoxyphenyl)ureido)phenyl)thiazol-2 -yl)cyclohexane carboxylic acid;

Methyl 4-(5-(4-(3-phenylureido)phenyl)thiazol-2-yl)cyclohexanecarbo xylate;

4-(5-(4-(3-Phenylureido)phenyl)thiazol-2-yl)cyclohexaneca rboxylic acid;

Methyl 4-(5-(4-(4-t-butylbenzamido)phenyl)thiazol-2-yl)cyclohexane carboxylate;

4-(5-(4-(4-t-Butylbenzamido)phenyl)thiazol-2-yl)cyclohexa necarboxylic acid;

Methyl 4-(5-(4-(2-chlorobenzamido)phenyl)thiazol-2-yl) cyclohexane carboxylate;

4-(5-(4-(2-Chlorobenzamido)phenyl)thiazol-2-yl)cyclohexan ecarboxylic acid;

Methyl 4-(5-(4-(5-phenyloxazole-2-carboxamido)phenyl)thiazol-2-yl) cyclohexane carboxylate;

4-(5-(4-(5-Phenyloxazole-2-carboxamido)phenyl)thiazol-2-yl)c yclohexane carboxylic acid;

Methyl 4-(5-(4-(3-(4-methoxyphenyl)thioureido)phenyl)thiazol-2-yl) cyclo

hexanecarboxylate;

Methyl 4-(5-(4-(3-(4-chlorophenyl)thioureido)phenyl)thiazol-2-yl)cy clo

hexanecarboxylate;

Methyl 4-(5-(4-(3-(2-chlorophenyl)ureido)phenyl)oxazol-2-yl)cyclohe xane carboxylate;

4-(5-(4-(3-(2-Chlorophenyl)ureido)phenyl)oxazol-2-yl)cycl ohexanecarboxylic

acid;

Methyl 4-(5-(4-(3-phenylureido)phenyl)oxazol-2-yl)cyclohexanecarbox ylate; 4-(5-(4-(3-Phenylureido)phenyl)oxazol-2-yl)cyclohexanecarbox ylic acid;

Methyl 4-(5-(4-(3-(3-chlorophenyl)ureido)phenyl)oxazol-2-yl)cyclohe xane carboxylate;

4-(5-(4-(3-(3-Chlorophenyl)ureido)phenyl)oxazol-2-yl)cycl ohexanecarboxylic acid;

Methyl 4-(5-(4-(3-(2-methoxyphenyl)ureido)phenyl)oxazol-2-yl) cyclohexane carboxylate;

4-(5-(4-(3-(2-Methoxyphenyl)ureido)phenyl)oxazol-2-yl)cycloh exane carboxylic acid; Methyl 4-(5-(4-(2-chlorobenzamido)phenyl)oxazol-2-yl)cyclohexane carboxylate; 4-(5-(4-(2-Chlorobenzamido)phenyl)oxazol-2-yl)cyclohexanecar boxylic acid;

Methyl 4-(5-(4-(4-t-butylbenzamido)phenyl)oxazol-2-yl)cyclohexane carboxylate; 4-(5-(4-(4-t-Butylbenzamido)phenyl)oxazol-2-yl)cyclohexaneca rboxylic acid;

(1 r,4r)-Methyl 4-(3-(4-(3-(2-chlorophenyl)ureido)phenyl)-1 ,2,4-oxadiazol-5-yl) cyclohexanecarboxylate;

(1 r,4r)-4-(3-(4-(3-(2-Chlorophenyl)ureido)phenyl)-1 ,2,4-oxadiazol-5-yl)cyclo hexanecarboxylic acid;

(1 r,4r)-Methyl 4-(3-(4-(3-(2,4-difluorophenyl)ureido)phenyl)-1 ,2,4-oxadiazol-5-yl) cyclohexanecarboxylate;

(1 r,4r)-4-(3-(4-(3-(2,4-Difluorophenyl)ureido)phenyl)-1 ,2,4-oxadiazol-5-yl)

cyclohexanecarboxylic acid;

(1 r,4r)-Methyl 4-(3-(4-(3-p-tolylureido)phenyl)-1 ,2,4-oxadiazol-5-yl)cyclo hexane carboxylate;

(1 r,4r)-4-(3-(4-(3-p-Tolylureido)phenyl)-1 ,2,4-oxadiazol-5-yl)cyclohexane carboxylic acid;

(1 r,4r)-Methyl 4-(3-(4-(3-(3-chlorophenyl)ureido)phenyl)-1 ,2,4-oxadiazol-5-yl) cyclo hexanecarboxylate;

(1 r,4r)-4-(3-(4-(3-(3-Chlorophenyl)ureido)phenyl)-1 ,2,4-oxadiazol-5-yl)cyclo hexanecarboxylic acid;

(1 r,4r)-Methyl 4-(3-(4-(3-(4-chloro-2-phenoxyphenyl)ureido)phenyl)-1 ,2,4-oxadiazol-5- yl)cyclohexanecarboxylate;

(1 r,4r)-4-(3-(4-(3-(4-Chloro-2-phenoxyphenyl)ureido)phenyl)-1 ,2,4-oxadiazol-5-yl) cyclohexanecarboxylic acid;

(1 r,4r)-Methyl 4-(3-(4-(4-tert-butylbenzamido)phenyl)-1 ,2,4-oxadiazol-5-yl)

cyclohexanecarboxylate; (1 r,4r)-4-(3-(4-(4-t-Butylbenzamido)phenyl)-1 ,2,4-oxadiazol-5-yl)cyclohexane carboxylic acid;

(1 r,4r)-Methyl 4-(3-(4-biphenyl-4-ylcarboxamidophenyl)-1 ,2,4-oxadiazol-5-yl) cyclohexanecarboxylate;

(1 r,4r)-4-(3-(4-Biphenyl-4-ylcarboxamidophenyl)-1 ,2,4-oxadiazol-5-yl)cyclo

hexanecarboxylic acid;

(1 r,4r)-Methyl 4-(3-(4-(4-(trifluoromethoxy)benzamido)phenyl)-1 ,2,4-oxadiazol -5- yl)cyclohexanecarboxylate;

(1 r,4r)-4-(3-(4-(4-(Trifluoromethoxy)benzamido)phenyl)-1 ,2,4-oxadiazol-5-yl) cyclohexanecarboxylic acid;

Methyl 4-(5-(4-(3-(3,5-difluorophenyl)ureido)phenyl)thiazol-2-yl)-2 ,2-dimethylbutanoate; 4-(5-(4-(3-(3,5-Difluorophenyl)ureido)phenyl)thiazol-2-yl)-2 ,2-dimethylbutanoic acid; Sodium salt of 4-(5-(4-(3-(3,5-difluorophenyl)ureido)phenyl)thiazol-2-yl)-2 ,2- dimethylbutanoate;

Methyl 2,2-dimethyl-4-(5-(4-(3-(2,4,5-trifluorophenyl)ureido)phenyl )thiazol-2-yl) butanoate;

2,2-Dimethyl-4-(5-(4-(3-(2,4,5-trifluorophenyl)ureido)phenyl )thiazol-2-yl)butanoic acid; Sodium salt of 2,2-dimethyl-4-(5-(4-(3-(2,4,5-trifluorophenyl)ureido)phenyl ) thiazol-2- yl)butanoate;

Methyl 2,2-dimethyl-4-(5-(4-(piperidine-1 -carboxamido)phenyl)thiazol-2-yl) butanoate; 2,2-Dimethyl-4-(5-(4-(piperidine-1 -carboxamido)phenyl)thiazol-2-yl)butanoic acid; Methyl 2,2-dimethyl-4-(5-(4-(morpholine-4-carboxamido)phenyl)thiazo l-2-yl) butanoate; 2,2-Dimethyl-4-(5-(4-(morpholine-4-carboxamido)phenyl)thiazo l-2-yl)butanoic acid; Methyl 2,2-dimethyl-4-(5-(4-(4-methylpiperazine-1 -carboxamido)phenyl)thiazol-2- yl)butanoate;

2,2-Dimethyl-4-(5-(4-(4-methylpiperazine-1 -carboxamido)phenyl)thiazol-2-yl) butanoic acid hydrochloride;

Methyl 4-(5-(4-(3-(2,3-dihydrobenzo[b][1 ,4]dioxin-6-yl)ureido)phenyl)thiazol-2-yl)-2,2- dimethylbutanoate;

4-(5-(4-(3-(2,3-Dihydrobenzo[b][1 ,4]dioxin-6-yl)ureido)phenyl)thiazol-2-yl)-2,2- dimethylbutanoic acid;

Methyl 4-(5-(4-(3-(1 H-tetrazol-5-yl)ureido)phenyl)thiazol-2-yl)-2,2-dimethyl butanoate; 4-(5-(4-(3-(1 H-Tetrazol-5-yl)ureido)phenyl)thiazol-2-yl)-2,2-dimethylbuta noic acid; Methyl 4-(5-(4-(3-(2-methoxyethyl)ureido)phenyl)thiazol-2-yl)-2,2-d imethyl butanoate; 4-(5-(4-(3-(2-Methoxyethyl)ureido)phenyl)thiazol-2-yl)-2,2-d imethylbutanoic acid;

Methyl 4-(5-(4-(3-(2,3-dihydro-1 H-inden-2-yl)ureido)phenyl)thiazol-2-yl)-2,2- dimethylbutanoate;

4-(5-(4-(3-(2,3-Dihydro-1 H-inden-2-yl)ureido)phenyl)thiazol-2-yl)-2,2-dimethyl butanoic acid;

Methyl 4-(5-(4-(3-cyclohexyl-3-methylureido)phenyl)thiazol-2-yl)-2, 2-dimethyl butanoate;

4-(5-(4-(3-Cyclohexyl-3-methylureido)phenyl)thiazol-2-yl)-2, 2-dimethylbutanoic acid; Methyl 2,2-dimethyl-4-(5-(4-(3-(3,4,5-trifluorophenyl)ureido)phenyl )thiazol-2-yl) butanoate;

2,2-Dimethyl-4-(5-(4-(3-(3,4,5-trifluorophenyl)ureido)phenyl )thiazol-2-yl)butanoic acid; Sodium salt of 2,2-dimethyl-4-(5-(4-(3-(3,4,5-trifluorophenyl) ureido) phenyl) thiazol-2- yl)butanoate;

Methyl 2,2-dimethyl-4-(5-(4-(3-(2-(piperidin-1 -yl)ethyl)ureido)phenyl)thiazol-2-yl) butanoate;

2,2-Dimethyl-4-(5-(4-(3-(2-(piperidin-1 -yl)ethyl)ureido)phenyl)thiazol-2-yl) butanoic acid; Methyl 4-(5-(4-(3-benzylureido)phenyl)thiazol-2-yl)-2,2-dimethylbut anoate;

4-(5-(4-(3-Benzylureido)phenyl)thiazol-2-yl)-2,2-dimethyl butanoic acid;

Methyl 4-(5-(4-(4,4-difluoropiperidine-1 -carboxamido)phenyl)thiazol-2-yl)-2,2- dimethylbutanoate;

4-(5-(4-(4,4-Difluoropiperidine-1 -carboxamido)phenyl)thiazol-2-yl)-2,2-dimethylbutanoic acid;

Methyl 2,2-dimethyl-4-(5-(4-(4-phenylpiperidine-1 -carboxamido)phenyl)thiazol-2- yl)butanoate;

2,2-Dimethyl-4-(5-(4-(4-phenylpiperidine-1 -carboxamido)phenyl)thiazol-2-yl) butanoic acid;

Methyl 2,2-dimethyl-4-(5-(4-(4-phenylpiperidine-1 -carboxamido)phenyl)thiazol-2- yl)butanoate;

4-(5-(4-(3-(4-Cyanobenzyl)ureido)phenyl)thiazol-2-yl)-2,2-di methylbutanoic acid;

Methyl 4-(5-(4-(3-(2-fluorophenyl)thioureido)phenyl)thiazol-2-yl)-2 ,2-dimethyl butanoate; 4-(5-(4-(3-(2-Fluorophenyl)thioureido)phenyl)thiazol-2-yl)-2 ,2-dimethylbutanoic acid; Methyl 4-(5-(4-(3-(2-fluorophenyl)guanidino)phenyl)thiazol-2-yl)-2, 2-dimethyl butanoate; 4-(5-(4-(3-(2-Fluorophenyl)guanidino)phenyl)thiazol-2-yl)-2, 2-dimethylbutanoic acid; Methyl 4-(5-(4-(3-(2-fluorophenyl)-2-methylguanidino)phenyl)thiazol -2-yl)-2,2- dimethylbutanoate;

4-(5-(4-(3-(2-Fluorophenyl)-2-methylguanidino)phenyl)thiazol -2-yl)-2,2-dimethylbutanoic acid;

Methyl 4-(5-(4-(2-cyano-3-(2-fluorophenyl)guanidino)phenyl)thiazol- 2-yl)-2,2- dimethylbutanoate;

4-(5-(4-(2-Cyano-3-(2-fluorophenyl)guanidino)phenyl)thiazol- 2-yl)-2,2-dimethyl butanoic acid;