IP Library Granted Patent US 8,835,428
Granted Patent B2
US 8,835,428 · App. 13/034,192 · Granted Sep 16, 2014

Diacylglycerol acyltransferase inhibitors

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Quick Facts
Patent No.
US 8,835,428
App. No.
13/034,192
Granted
Sep 16, 2014
Kind
B2
Abstract

The present invention relates to isoxazole, thiazole and oxidiazole derivatives, processes for their preparation, pharmaceutical compositions containing them and their use as medicaments, in particular to the use of these compounds in the prevention and treatment of diseases or disorders mediated by diacylglycerol acyltransferase (DGAT), particularly DGAT1.

Claims (561)

1. A compound of formula (I),

wherein,

--- dotted line represents the variable attachment of -L 1 -R A to the specified carbon atoms of the phenyl ring,

R A is cycloalkyl, alkylaryl, aryl, heteroaryl or heterocycle; wherein each of cycloalkyl, alkylaryl, aryl, heteroaryl and heterocycle is optionally substituted;

R x is H, halogen or alkyl;

R 1 and R 2 are independently selected from H, alkyl, alkenyl, alkynyl, cycloalkyl, alkylcycloalkyl, aryl, alkylaryl, alkylheteroaryl, heterocycle and heteroaryl;

L 1 is —O—, —NR 3 (CR 4 R 5 ) a NR 3 —, —(CR 4 R 5 ) b NR 3 —, —SO 2 NH—or —SO 2 NHCONH—;

R 3 is H, —COR 1 , —COOR 1 , —CONR 1 R 2 , alkyl, alkenyl, alkynyl, cycloalkyl or alkylcycloalkyl;

R 4 and R 5 are independently selected from H, —OR 6 , —COOR 6 , —CONR 6 R 7 , alkyl, alkenyl, alkynyl, cycloalkyl, alkylcycloalkyl, aryl, heteroaryl, alkylaryl, alkylheteroaryl and alkytheterocycle;

or R 4 and R 5 together are ═O, ═S or ═NR 8 ;

R 6 and R 7 are independently selected from H, alkyl, cycloalkyl and heterocycle;

Y is

wherein,

L 2 is —C(═O)—NR Z —, —C(═S)—NR Z —, —C(═NR 8 )—NR Z —, —C(SR 9 )═N—, —C(═O), —C(═S) or —SO 2 NR Z —;

R Z is H, or alkyl;

R 8 is H, —OR 9 , —COR 9 , —COOR 9 , —CONR 6 R 7 , —SO 2 R 9 or —SO 2 NR 6 R 7 ;

R 9 is absent or is selected from H or alkyl;

R B is —(CR 10 R 11 ) c — or —(NR 12 )(CR 10 R 11 ) c ; wherein c is an integer from 1 to 3;

or OR 9 , C(O), R B and L 2 ; or R B and L 2 ; or R B , C(O) and OR 9 together form a 5 to 7-membered ring selected from heteroaryl and heterocycle;

R 10 , R 11 , and R 12 are independently selected from: H, aryl, C 1 -C 6 alkyl optionally substituted with OH or C 1 -C 4 alkoxy; or (C 1 -C 6 )alkylaryl optionally substituted with OH;

or R 12 and R 10 or R 11 together with the respective N and C atoms to which they are attached, form a 3 to 6 membered heterocyclic or heteroaryl ring;

or R 12 and R 11 of —(CR 10 R 11 ) c wherein c is an integer 1 together with the C atom to which they are attached form a 3 to 6-membered cycloalkyl ring;

or R 10 and R 11 of —(CR 10 R 11 ) c wherein c is an integer 1 together with the C atom to which they are attached form alkenylene;

R Y is —H, halogen, —CN, OH, alkyl or unsubstituted aryl;

with the proviso that when L 1 is —(CR 4 R 5 ) b NR 3 —, L 2 is —C(═O)—NR Z — is and R B is —(CR 10 R 11 ) c , then (a) c is the integer 1; and (b) R A is heteroaryl or heterocycle, wherein the heteroaryl or heterocycle is selected from indolyl, isoindolyl, indolizinyl, benzofuranyl, benzothienyl, quinolinyl, isoquinolinyl, benzopyranyl, indazolyl, benzimidazolyl, benzothiazolyl, coumarinyl, benzoisothiazolyl, benzodioxolyl, benzoxazolyl, benzoisoxazolyl, quinoxalinyl, quinazolinyl, phthalazinyl, pteridinyl, cinnolinyl, chromonyl, pyrrolopyridyl, furopyridinyl, purinyl, benzothiadiazolyl, benzooxadiazolyl, benzotriazolyl, acridinyl, benzothiadiazolyl, benzotriazinyl, carbazolyl, dibenzofuranyl, dibenzothienyl, phenanthridinyl and xanthenyl; and wherein the heteroaryl or heterocycle is optionally substituted with one or more groups selected from halogen, oxo, thio, nitro, —CN, —OR 1 , —S(═O) m R 1 , —S(═O) 1-2 NR 1 R 2 , —OCOR 1 , —SCOR 1 , —NR 1 R 2 , —NR 1 COR 2 , —NR 1 COOR 2 , —NR 1 SOR 2 , —NR 1 SO 2 R 2 , —NR 1 CONR 1 R 2 , —COR 1 , —COOR 1 , —CONR 1 R 2 , alkyl, alkenyl, alkynyl, cycloalkyl, alkylcycloalkyl, aryl, alkylaryl, heterocyclyl, alkylheterocyclyl, heteroaryl and alkylheteroaryl; wherein R 1 and R 2 are independently selected from H, alkyl, alkenyl, alkynyl, cycloalkyl, alkylcycloalkyl, aryl, alkylaryl, heterocyclyl, alkytheterocyclyl, heteroaryl and alkylheteroaryl;

a is an integer from 1 to 5;

b is 0 or an integer from 1 to 5;

m is 0 or an integer from 1 to 2;

p is an integer from 1 to 4;

* indicates the point of attachment;

or a stereoisomer, a tautomer or a pharmaceutically acceptable salt thereof.

2. A compound according to claim 1 having formula (Iaa),

wherein,

--- dotted line represents the variable attachment of -L 1 -R A to the specified carbon atoms of the phenyl ring,

R A is cycloalkyl, aryl, alkylaryl, heteroaryl or heterocycle; wherein each of cycloalkyl, aryl, alkylaryl, heteroaryl and heterocycle is optionally substituted;

R X is H, halogen or alkyl;

R Y is selected from H, halogen, —CN, OH, alkyl or unsubstituted aryl;

L 1 is —O—, —NR 3 (CR 4 R 5 ) a NR 3 —, —(CR 4 R 5 ) b NR 3 —, —SO 2 NH—, or —SO 2 NHCONH—;

L 2 is —C(═O), —C(═O)—NR Z —, —C(═S)—NR Z —, —C(═NR 8 )—NR Z —, —C(SR 9 )═N— or —SO 2 NR Z —;

R B is —(CR 10 R 11 ) c — or —(NR 12 )(CR 10 R 11 ) c , wherein c is an integer from 1 to 3;

R 9 is absent or is selected from H or alkyl;

or R B , C(O), OR 9 and L 2 ; or R B and L 2 ; or R B , C(O) and OR 9 together form a 5 to 7-membered ring selected from heteroaryl and heterocycle;

R 1 and R 2 are independently selected from H, alkyl, alkenyl, alkynyl, cycloalkyl, alkylcycloalkyl, aryl, alkylaryl, alkylheteroaryl, heterocycle and heteroaryl;

R 3 is —H, —COR 1 , —COOR 1 , —CONR 1 R 2 , alkyl, alkenyl, alkynyl, cycloalkyl or alkylcycloalkyl;

R 4 and R 5 are independently selected from —H, —OR 6 , —COOR 6 , —CONR 6 R 7 , alkyl, alkenyl, alkynyl, cycloalkyl, alkylcycloalkyl, aryl, heteroaryl, alkylaryl, alkylheteroaryl and alkytheterocycle;

or R 4 and R 5 together are ═O, ═S or ═NR 8 ;

R 6 and R 7 are independently selected from H, alkyl, cycloalkyl and heterocycle;

R Z is —H, or alkyl;

R 8 is —H, —OR 9 , —COR 9 , —COOR 9 , —CONR 6 R 7 , —SO 2 R 9 or —SO 2 NR 6 R 7 ;

R 10 , R 11 and R 12 are independently selected from H, aryl, C 1 -C 6 alkyl optionally substituted with OH or C 1 -C 4 alkoxy; or (C 1 -C 6 )alkylaryl optionally substituted with OH;

or R 12 and R 10 or R 11 together with the respective N and C atoms to which they are attached, form a 3 to 6-membered, heteroaryl or heterocyclic ring;

or R 10 and R 11 of —(CR 10 R 11 ) c wherein c is the integer 1, together with the C atom to which they are attached form a 3 to 6-membered cycloalkyl ring;

or R 10 and R 11 of —(CR 10 R 11 ) c wherein c is the integer 1 together with the C atom to which they are attached form alkenylene;

a is an integer from 1 to 5;

b is 0 or an integer from 1 to 5;

m is 0 or an integer from 1 to 2;

p is an integer from 1 to 4;

with the proviso that When L 2 is —C(═O)—NR Z —, L 1 is —(CR 4 R 5 ) b NR 3 —, and R B is —(CR 10 R 11 ) c then (a) c is the integer 1; and (b) R A is heteroaryl or heterocycle, wherein the heteroaryl or heterocycle is selected from indolyl, isoindolyl, indolizinyl, benzofuranyl, benzothienyl, quinolinyl, isoquinolinyl, benzopyranyl, indazolyl, benzimidazolyl, benzothiazolyl, benzoisothiazolyl, benzodioxolyl, benzoxazolyl, benzoisoxazolyl, quinoxalinyl, quinazolinyl, phthalazinyl, pteridinyl, cinnolinyl, chromonyl, coumarinyl, pyrrolopyridyl, furopyridinyl, purinyl, benzothiadiazolyl, benzooxadiazolyl, benzotriazolyl, benzothiadiazolyl, benzotriazinyl, carbazolyl, dibenzofuranyl, dibenzothienyl, acridinyl, phenanthridinyl and xanthenyl; and wherein the heteroaryl or heterocycle is optionally substituted with one or more groups selected from halogen, oxo, thio, nitro, —CN, —OR 1 , —S(═O) m R 1 , —S(═O) 1-2 NR 1 R 2 , —OCOR 1 , —SCOR 1 , —NR 1 R 2 , —NR 1 COR 2 , —NR 1 COOR 2 , —NR 1 SOR 2 , —NR 1 SO 2 R 2 , —NR 1 CONR 1 R 2 , —COR 1 , —COOR 1 , —CONR 1 R 2 , alkyl, alkenyl, alkynyl, cycloalkyl, alkylcycloalkyl, aryl, alkylaryl, heterocyelyl, alkylheterocyclyl, heteroaryl and alkylheteroaryl; wherein R 1 and R 2 are independently selected from H, alkyl, alkenyl, alkynyl, cycloalkyl, alkylcycloalkyl, aryl, alkylaryl, heterocyclyl, alkylheterocyclyl, heteroaryl and alkylheteroaryl;

or a stereoisomer, a tautomer or a pharmaceutically acceptable salt thereof.

3. A compound according to claim 2 , having formula (Iab),

wherein,

R A is cycloalkyl, alkylaryl, aryl, heteroaryl or heterocycle; wherein each of cycloalkyl, alkylaryl, aryl, heteroaryl and heterocycle is optionally substituted;

R X is H, halogen or alkyl;

R Y is selected from H, halogen, —CN, OH, alkyl, or unsubstituted aryl;

R 1 and R 2 are independently selected from H, alkyl, alkenyl, alkynyl, cycloalkyl, alkylcycloalkyl, aryl, alkylaryl, alkylheteroaryl, heterocycle and heteroaryl;

L 1 is —O—, —NR 3 (CR 4 R 5 ) a NR 3 —, —(CR 4 R 5 ) b NR 3 —, —SO 2 NH— or —SO 2 NHCONH—;

R 3 is H, —COR 1 , —COOR 1 , —CONR 1 R 2 , alkyl, alkenyl, alkynyl, cycloalkyl or alkylcycloalkyl;

R 4 and R 5 are independently selected from H, —OR 6 , —COOR 6 , —CONR 6 R 7 , alkyl, alkenyl, alkynyl, cycloalkyl, alkylcycloalkyl, aryl, heteroaryl, alkylaryl, alkylheteroaryl and alkytheterocycle;

or R 4 and R 5 together are ═O or ═S or ═NR 8 ;

R 6 and R 7 are independently selected from H, alkyl, cycloalkyl and heterocycle;

L 2 is —C(═O)—, —C(═O)—NR Z —, —C(═S)—NR Z —, —C(═NR 8 )—NR Z , —C(SR 9 )═N— or —SO 2 NR Z —,

R Z is H or alkyl;

R 8 is H, —OR 9 , —COR 9 , —COOR 9 , —CONR 6 R 7 , —SO 2 R 9 or —SO 2 NR 6 R 7 ;

R 9 is absent or is selected from H or alkyl;

R B is —(CR 10 R 11 ) c — or —(NR 12 )(CR 10 R 11 ) c ; wherein c is an integer from 1 to 3;

or R B , C(O), OR 9 and L 2 ; or R B and L 2 ; or R B , C(O) and OR 9 , together form a 5 to 7-membered ring selected from heteroaryl or heterocycle;

R 10 , R 11 and R 12 are independently selected from: H, aryl, C 1 -C 6 alkyl optionally substituted with OH or C 1 -C 4 alkoxy; or (C 1 -C 6 )alkylaryl optionally substituted with OH;

or R 12 and R 10 or R 11 , together with the respective N and C atoms to which they are attached, form a 3 to 6-membered heteroaryl or heterocyclic ring;

or R 10 and R 11 of —(CR 10 R 11 ) c wherein c is the integer 1, together with the C atony to which they are attached form a 3 to 6-membered cycloalkyl ring;

or R 10 and R 11 of —(CR 10 R 11 ) c wherein c is the integer 1 together with the C atom to which they are attached form alkenylene;

a is the integer 1;

b is 0 or an integer from 1 to 5;

m is 0 or the integer 1 or 2;

p is an integer from 1 to 4;

with the proviso that when L 2 is —C(═O)—NR Z —, L 1 is —(CR 4 R 5 ) b NR 3 —, and R B is —(CR 10 R 11 ) c , then (a) c is the integer 1 and (b) R A is heteroaryl or heterocycle, wherein the heteroaryl or heterocycle is selected from indolyl, isoindolyl, indolizinyl, benzofuranyl, benzothienyl, quinolinyl, isoquinolinyl, benzopyranyl, indazolyl, benzimidazolyl, benzothiazolyl, benzoisothiazolyl, benzodioxolyl, benzoxazolyl, benzoisoxazolyl, quinoxalinyl, quinazolinyl, phthalazinyl, pteridinyl, cinnolinyl, chromonyl, coumarinyl, pyrrolopyridyl, furopyridinyl, purinyl, benzothiadiazolyl, benzooxadiazolyl, benzotriazolyl, benzothiadiazolyl, benzotriazinyl, carbazolyl, dibenzofuranyl, dibenzothienyl, acridinyl, phenanthridinyl and xanthenyl; and wherein the heteroaryl or heterocycle is optionally substituted with one or more groups selected from halogen, oxo, thio, nitro, —CN, —OR 1 , —S(═O) m R 1 , —S(═O) 1-2 NR 1 R 2 , —OCOR 1 , —SCOR 1 , —NR 1 R 2 , —NR 1 COR 2 , —NR 1 COOR 2 , —NR 1 SOR 2 , —NR 1 SO 2 R 2 , —NR 1 CONR 1 R 2 , —COR 1 , —COOR 1 , —CONR 1 R 2 , alkyl, alkenyl, alkynyl, cycloalkyl, alkylcycloalkyl, aryl, alkylaryl, heterocyclyl, alkylheterocyclyl, heteroaryl and alkylheteroaryl; wherein R 1 and R 2 are independently selected from H, alkyl, alkenyl, alkynyl, cycloalkyl, alkylcycloalkyl, aryl, alkylaryl, heterocyclyl, alkylheterocyclyl, heteroaryl and alkylheteroaryl;

or a stereoisomer, a tautomer or a pharmaceutically acceptable salt thereof.

4. A compound according to claim 2 , having formula (Iac),

wherein,

R A is cycloalkyl, aryl, heteroaryl or heterocycle; wherein each of cycloalkyl, aryl, heteroaryl and heterocycle is optionally substituted;

R X and R Y are independently selected from H, halogen, —CN, —OR 1 , —S(═O) m R 1 , —OCOR 1 , —SCOR 1 , —NR 1 R 2 , —NR 1 COR 2 , —NR 1 COOR 2 , —NR 1 SO 2 R 2 , —NR 1 CONR 2 , —COR 1 , —COOR 1 , —CONR 1 R 2 , alkyl, alkenyl, alkynyl, cycloalkyl, alkylcycloalkyl, aryl, alkylaryl, alkylheteroaryl or heteroaryl;

R 1 and R 2 are independently selected from H, alkyl, alkenyl, alkynyl, cycloalkyl, alkylcycloalkyl, aryl, alkylaryl, alkylheteroaryl, heterocycle and heteroaryl;

L 2 is —C(═O)—NR Z —, —C(═S)—NR Z —, —C(═NR 8 )—NR Z — or —SO 2 NR Z —;

R Z is —H, —COR 1 , —COOR 1 , —CONR 1 R 2 , alkyl, alkenyl, alkynyl, cycloalkyl or alkylcycloalkyl;

R 8 is H, —OR 9 , —COR 9 , —COOR 9 , —CONR 6 R 7 , —SO 2 R 9 or —SO 2 NR 6 R 7 ;

R 6 and R 7 are independently selected from H, alkyl, cycloalkyl and heterocycle;

R 3 is H, —COR 1 , —COOR 1 , —CONR 1 R 2 , alkyl, alkenyl, alkynyl, cycloalkyl or alkylcycloalkyl;

R 9 is absent or is selected from H, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, alkylcycloalkyl, alkylaryl, alkylheteroaryl, heterocycle and heteroaryl;

R B is —(CR 10 R 11 ) c — or —(NR 12 )(CR 10 R 11 ) c ; wherein c is an integer from 1 to 3;

or R B , C(O), OR 9 and L 2 ; or R B and L 2 ; or R B C(O) and OR 9 , together form a 5 to 7-membered ring selected from cycloalkyl, aryl, heteroaryl and heterocycle;

R 10 , R 11 and R 12 are independently selected from H or the groups alkyl, alkenyl, alkynyl, cycloalkyl, alkylcycloalkyl, aryl, alkylaryl, alkylheteroaryl, heterocycle and heteroaryl;

or R 12 and R 10 or R 11 together with the respective N and C atoms to which they are attached, form a 3 to 6 membered heterocyclic or heteroaryl ring;

or R 10 and R 11 of —(CR 10 R 11 ) c wherein c is the integer 1, together with the C atom to which they are attached form a 3 to 6-membered cycloalkyl ring;

m is 0 or an integer from 1 to 2;

p is an integer from 1 to 4;

with the proviso that when L 2 is —C(═O)—NR Z — and R B is —(CR 10 R 11 ) c , then (i) c is the integer 1 and (ii) R A is heteroaryl or heterocycle, wherein the heteroaryl or heterocycle is selected from indolyl, isoindolyl, indolizinyl, benzofuranyl, benzothienyl, quinolinyl, isoquinolinyl, benzopyranyl, indazolyl, benzimidazolyl, benzothiazolyl, benzoisothiazolyl, benzodioxolyl, benzoxazolyl, benzoisoxazolyl, quinoxalinyl, quinazolinyl, phthalazinyl, pteridinyl, cinnolinyl, chromonyl, coumarinyl, pyrrolopyridyl, furopyridinyl, purinyl, benzothiadiazolyl, benzooxadiazolyl, benzotriazolyl, benzothiadiazolyl, benzotriazinyl, carbazolyl, dibenzofuranyl, dibenzothienyl, acridinyl, phenanthridinyl and xanthenyl; and wherein the heteroaryl or heterocycle is optionally substituted with one or more groups selected from halogen, oxo, thio, nitro, —CN, —OR 1 , —S(═O) m R 1 , —S(═O) 1-2 NR 1 R 2 , —OCOR 1 , —SCOR 1 , —NR 1 R 2 , —NR 1 COR 2 , —NR 1 COOR 2 , —NR 1 SOR 2 , —NR 1 SO 2 R 2 , —NR 1 CONR 2 R 2 , —COR 1 , —COOR 1 , —CONR 1 R 2 , alkyl, alkenyl, alkynyl, cycloalkyl, alkylcycloalkyl, aryl, alkylaryl, heterocyclyl, alkylheterocyclyl, heteroaryl and alkylheteroaryl; Wherein R 1 and R 2 are independently selected from H, alkyl, alkenyl, alkynyl, cycloalkyl, alkylcycloalkyl, aryl, alkylaryl, heterocyclyl, alkylheterocyclyl, heteroaryl and alkylheteroaryl;

or a stereoisomer or a tautomer thereof or a pharmaceutically acceptable salt or a pharmaceutically acceptable solvate thereof.

5. A compound according to claim 2 having formula (Iae),

wherein,

R A is cycloalkyl, alkylaryl, aryl, heteroaryl or heterocycle; wherein each of cycloalkyl, alkylaryl, aryl, heteroaryl and heterocycle is optionally substituted;

R X is H, halogen or alkyl;

R Y is selected from H, halogen, —CN, OH, alkyl, or unsubstituted aryl;

R 1 and R 2 are independently selected from H, alkyl, alkenyl, alkynyl, cycloalkyl, alkylcycloalkyl, aryl, alkylaryl, alkylheteroaryl, heterocycle and heteroaryl;

R 3 is H, —COR 1 , —COOR 1 , —CONR 1 R 2 , alkyl, alkenyl, alkynyl, cycloalkyl or alkylcycloalkyl;

L 2 is —C(═O)—, —C(═O)—NR Z —, —C(═S)—NR Z —, —C(═NR 8 )—NR Z —, —C(SR 9 )═N— or —SO 2 NR Z —;

R Z is H;

R 8 is H, —OR 9 , —COR 9 , —COOR 9 , —CONR 6 R 7 , —SO 2 R 9 or —SO 2 NR 6 R 7 ;

R 6 and R 7 are independently selected from H, alkyl, cycloalkyl and heterocycle;

R 9 is H or alkyl;

R B is —(CR 10 R 11 ) c — or —(NR 12 )( CR 10 R 11 ) c ; wherein c is an integer from 1 to 3;

R 10 , R 11 and R 12 are independently selected from

H,

aryl,

C 1 -C 6 alkyl optionally substituted With OH or C 1 -C 4 alkoxy, or

(C 1 -C 6 )alkylaryl optionally substituted with OH;

or R 12 and R 10 or R 11 together with the respective N and C atoms to which they are attached, form a 3 to 6 membered heterocyclic or heteroaryl ring;

or R 10 and R 11 of —(CR 10 R 11 ) c wherein c is the integer 1, together with the C atom to which they are attached form a 3 to 6-membered cycloalkyl ring;

or R 10 and R 11 of —(CR 10 R 11 ) c wherein c is the integer 1 together with the C atom to which they are attached form alkenylene;

m is 0 or the integer 1 or 2;

p is an integer from 1 to 4;

or a stereoisomer, a tautomer or a pharmaceutically acceptable salt thereof.

6. A compound according to claim 2 , having formula (Iaf),

wherein,

R A is cycloalkyl, alkylaryl, aryl, heteroaryl or heterocycle; wherein the cycloalkyl, alkylaryl, aryl, heteroaryl or heterocyclyl is optionally substituted with one or more groups, which may be the same or different, selected from halogen, —CN, —COOR 1 , —OR 1 , —S(═O) m R 1 , alkyl, haloalkyl, cycloalkyl, aryl and heteroaryl;

R X is H, halogen or alkyl;

R Y is selected from H, halogen, —CN, OH or alkyl;

R 1 and R 2 are independently selected from H, alkyl, alkenyl, alkynyl, cycloalkyl or aryl;

R 3 is H or alkyl;

L 2 is —C(═O)—, —C(═O)—NR Z , —C(═S)—NR Z —, —C(═NR 8 _—NR Z —, —C(SR 9 )═N— or —SO 2 NR Z —;

R Z is H or alkyl;

R 8 is H, —OR 9 , —COR 9 , —COOR 9 , —CONR 6 R 7 , —SO 2 R 9 or —SO 2 NR 6 R 7 ;

R 6 and R 7 are independently selected from H, alkyl, cycloalkyl and heterocycle;

R 9 is H or alkyl;

R B is —(CR 10 R 11 ) c — or —(NR 12 )(CR 10 R 11 ) c ; wherein c is an integer from 1 to 3;

R 10 , R 11 and R 12 are independently selected from

H,

aryl,

C 1 -C 6 alkyl optionally substituted with OH or C 1 -C 4 alkoxy, or

(C 1 -C 6 )alkylaryl optionally substituted with OH;

or R 12 and R 10 or R 11 together with the respective N and C atoms to which they are attached, form a 3 to 6 membered heterocyclic or heteroaryl ring;

or R 10 and R 11 of —(CR 10 R 11 ) c wherein c is an integer 1, together with the C atom to which they are attached form a 3 to 6-membered cycloalkyl ring;

or R 10 and R 11 of —(CR 10 R 11 ) c wherein c is the integer 1 together with the C atom to which they are attached form alkenylene;

m is 0 or the integer 1 or 2;

p is an integer from 1 to 4;

or a stcrcoisomer, a tautomer or a pharmaceutically acceptable salt thereof.

7. A compound according claim 2 , having formula (Iah),

wherein,

R A is cycloalkyl, alkylaryl, aryl, heteroaryl or heterocycle; wherein the cycloalkyl, alkylaryl, aryl, heteroaryl or heterocycle is optionally substituted with one or more groups, which may be the same or different, selected from halogen, cyano, —COOR 1 , —OR 1 , —S(═O) m R 1 , alkyl, haloalkyl, cycloalkyl, aryl and heteroaryl; wherein R 1 is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl or aryl;

R X is H, halogen or alkyl;

R Y is selected from H, halogen, —CN, OH, alkyl or unsubstituted aryl;

L 1 is —NH(C═O)NH—, —NH— or —(CO)NR 3 ; wherein R 3 is H or alkyl;

L 2 is —C(═O), —C(═O)—NR Z —, —C(═S)—NR Z —, —C(═NR 8 )—NR Z —, —C(SR 9 )═N— or —SO 2 NR Z —;

R Z is H or alkyl; R 8 is —OR 9 ; wherein R 9 is absent or is selected from H and alkyl;

R B is —(CR 10 R 11 ) c ; or —(NR 12 )(CR 10 R 11 ) c ; wherein c is an integer from 1 to 3;

or R B , C(O), OR 9 and L 2 ; or R B and L 2 ; or R B , C(O) and OR 9 , together form a 5 to 7-membered ring selected from heteroaryl or heterocycle; wherein the heteroaryl or heterocycle is optionally substituted with one or more groups selected from halogen, —CN, —OR 1 , —S(═O) m R 1 , —OCOR 1 , —SCOR 1 , —NR 1 NR 2 , —NR 1 COR 2 , —NR 1 COOR 2 , —NR 1 SO 2 R 2 , —NR 1 CONR 2 , —COR 1 , —COOR 1 , —CONR 1 R 2 , alkyl, alkenyl, alkynyl, cycloalkyl and alkylcycloalkyl;

wherein R 2 is selected from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl or aryl;

R 10 , R 11 and R 12 are independently selected from H, alkyl, and aryl, wherein the alkyl or aryl is optionally substituted with OH or —C 1 -C 4 alkoxy;

or R 12 and R 10 or R 11 together with the respective N and C atoms to which they are attached, together form a heterocyclic ring such as pyrrolidine ring;

or R 10 and R 11 of —CR 10 R 11 together with the C atom to which they are attached form a 3 to 6-membered cycloalkyl ring such as cyclopentyl ring;

or R 10 and R 11 of —(CR 10 R 11 ) c wherein c is the integer 1 together with the C atom to which they are attached form alkenylene;

m is 0 or the integer 1 or 2;

p is an integer from 1 to 4;

with the proviso that when L 1 is —NH—, L 2 is —C(═O)—NR Z — and

R B is —CR 10 R 11 then R A is heteroaryl or heterocycle selected from indolyl, isoindolyl, indolizinyl, benzofuranyl, benzothienyl, quinolinyl, isoquinolinyl, benzopyranyl, indazolyl, benzimidazolyl, benzothiazolyl, benzoisothiazolyl, benzodioxolyl, benzoxazolyl, benzoisoxazolyl, quinoxalinyl, quinazolinyl, phthalazinyl, pteridinyl, cinnolinyl, chromonyl, coumarinyl, pyrrolopyridyl, furopyridinyl, purinyl, benzothiadiazolyl, benzooxadiazolyl, benzotriazolyl, benzothiadiazolyl, benzotriazinyl, carbazolyl, dibenzoluranyl, dibenzothienyl, acridinyl, phenanthridinyl and xanthenyl; and wherein the heteroaryl or heterocycle is optionally substituted with one or more groups selected from halogen, oxo, thio, nitro, —CN, —OR 1 , —S(═O) m R 1 , —S(═O) 1-2 NR 1 R 2 , —OCOR 1 , —SCOR 1 , —NR 1 R 2 , —NR 1 COR 2 , —NR 1 COOR 2 , —NR 1 SOR 2 , —NR 1 SO 2 R 2 , —NR 1 CONR 1 R 2 , —COR 1 , —COOR 1 , —CONR 1 R 2 , alkyl, alkenyl, alkynyl, cycloalkyl, alkylcycloalkyl, aryl, alkylaryl, heterocyclyl, alkylheterocyclyl, heteroaryl and alkylheteroaryl; wherein R 1 and R 2 are independently selected from H, alkyl, alkenyl, alkynyl, cycloalkyl, alkylcycloalkyl, aryl, alkylaryl, heterocyclyl, alkylheterocyclyl, heteroaryl and alkylheteroaryl;

or a stereoisomer, a tautomer or a pharmaceutically acceptable salt thereof.

8. A compound according claim 2 , having formula (Iai),

wherein,

R A is cycloalkyl, alkylaryl, aryl, heteroaryl or heterocycle; wherein the cycloalkyl, alkylaryl, aryl, heteroaryl or heterocycle are optionally substituted with one or more groups, which may be the same or different, selected from cyano, halogen, —OR 1 , —COOR 1 , —S(═O) m R 1 , alkyl, haloalkyl, cycloalkyl, aryl and heteroaryl; R 1 is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl or aryl;

R X is H, halogen or alkyl;

R Y is H, halogen, —CN, OH, alkyl or unsubstituted aryl;

L 1 is —NH(C═O)NH—, —NH— or —(CO)NR 3 —, wherein R 3 is H or alkyl;

L 2 is —C(═O)—, —C(═O)—NR Z —, —C(═S)—NR Z —, —C(═NR 8 )—NR Z —, —C(SR 9 )═N— or —SO 2 NR Z —;

R Z is H or alkyl; R 8 is —OR 9 ; wherein R 9 is absent or is selected from H or alkyl;

R B is —(CR 10 R 11 ) c or —(NR 12 )(CR 10 R 11 ) c ; wherein c is an integer from 1 to 3;

or R B , C(O), OR 9 and L 2 ; or R B and L 2 ; or R B , C(O) and OR 9 , together form a 5 to 7-membered ring selected from heteroaryl or heterocycle; wherein the cycloalkyl, aryl, heteroaryl or heterocycle is optionally substituted with one or more groups selected from halogen, —CN, —OR 1 , —S(═O) m R 1 , —OCOR 1 , —SCOR 1 , —NR 1 R 2 , —NR 1 COR 2 , —NR 1 COOR 2 , —NR 1 SO 2 R 2 , —NR 1 CONR 2 , —COR 1 , —COOR 1 , —CONR 1 R 2 , alkyl, alkenyl, alkynyl, cycloalkyl and alkylcycloalkyl;

wherein R 2 is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl or aryl;

R 10 , R 11 and R 12 are independently selected from H, alkyl and aryl, wherein the alkyl or aryl is optionally substituted with OH or C 1 -C 4 alkoxy;

or R 12 and R 10 or R 11 together with the respective N and C atoms to which they are attached, together form a heterocyclic ring such as pyrrolidine ring;

or R 10 and R 11 of —CR 10 R 11 together with the C atom to which they are attached form a 3 to 6-membered cycloalkyl ring such as cyclopentyl ring;

or R 10 and R 11 of —(CR 10 R 11 ) c wherein c is the integer 1 together with the C atom to which they are attached form alkenylene;

m is 0 or the integer 1 or 2;

p is an integer from 1 to 4;

with the proviso that when L 1 is —NH—, L 2 is —C(═O)—NR Z — and R B is —CR 10 R 11 then R A is heteroaryl or heterocycle selected from indolyl, isoindolyl, indolizinyl, benzofuranyl, benzothienyl, quinolinyl, isoquinolinyl, benzopyranyl, indazolyl, benzimidazolyl, benzothiazolyl, benzoisothiazolyl, benzodioxolyl, benzoxazolyl, benzoisoxazolyl, quinoxalinyl, quinazolinyl, phthalazinyl, pteridinyl, cinnolinyl, chromonyl, coumarinyl, pyrrolopyridyl, furopyridinyl, purinyl, benzothiadiazolyl, benzooxadiazolyl, benzotriazolyl, benzothiadiazolyl, benzotriazinyl, carbazolyl, dibenzofuranyl, dibenzothienyl, acridinyl, phenanthridinyl and xanthenyl: and wherein the heteroaryl or heterocycle is optionally substituted with one or more groupS selected from halogen, oxo, thio, nitro, —CN, —OR 1 , —S(═O) m R 1 , —S(═O) 1-2 NR 1 R 2 , —OCOR 1 , —SCOR 1 , —NR 1 R 2 , —NR 1 COR 2 , —NR 1 COOR 2 , —NR 1 SOR 2 , —NR 1 SO 2 R 2 , —NR 1 CONR 1 R 2 , —COR 1 , —COOR 1 , —CONR 1 R 2 , alkyl, alkenyl, alkynyl, cycloalkyl, alkylcycloalkyl, aryl, alkylaryl, heterocyclyl, alkylheterocyclyl, heteroaryl and alkylheteroaryl; wherein R 1 and R 2 are independently selected from H, alkyl, alkenyl, alkynyl, cycloalkyl, alkylcycloalkyl, aryl, alkylaryl, heterocyclyl, alkylheterocyclyl, heteroaryl and alkylheteroaryl;

or a stereoisomer, a tautomer or a pharmaceutically acceptable salt thereof.

9. A compound according to claim 2 , having formula (Iaj),

wherein

R A is alkylaryl, aryl or heteroaryl; wherein the alkylaryl, aryl or heteroaryl is optionally substituted with one or more groups, which may be the same or different, selected from halogen, OR 1 , alkyl and haloalkyl; wherein R 1 is hydrogen or alkyl;

R X and R Y are hydrogen;

L 1 is —O—, —NR 3 (C═S)NR 3 —, —SO 2 NHCONH, —SO 2 NH—, —NR 3 (CO) 2 NR 3 —, wherein R 3 is H or alkyl;

L 2 is —C(═O)—, —C(═O)—NR Z —, —C(═S)—NR Z —, —C(═NR 8 )—NR Z —SO 2 NR Z —;

R Z is H; R 8 is —OR 9 , wherein R 9 is H or alkyl;

R B is —CR 10 R 11 ; or —(NR 12 )(CR 10 R 11 ) c ; wherein c is an integer from 1 to 3;

R 10 , R 11 and R 12 are independently selected from H and alkyl;

or R 12 and R 10 or R 11 together with the respective N and C atoms to which they are attached, together form a heterocyclic ring such as pyrrolidine ring;

m is 0 or the integer 1 or 2;

p is an integer from 1 to 4;

or a stereoisomer or a tautomer thereof or a pharmaceutically acceptable salt or a pharmaceutically acceptable solvate thereof.

10. A compound according to claim 1 selected from:

(S)-2-({3-[4-(6-Fluoro-benzothiazol-2-ylamino)-phenyl]-isoxazole-5-carbonyl}-amino)-3-methyl-butyric acid methyl ester;

(S)-2-({3-[4-(6-Fluoro-benzothiazol-2-ylamino)-phenyl]-isoxazole-5-carbothioyl}-amino)-3-methyl-butyric acid methyl ester;

(S)-2-({3-[4-(6-Fluoro-benzothiazol-2-ylamino)-phenyl]-N-hydroxy-isoxazole-5-carboximidoyl}-amino)-3-methyl-butyric acid methyl ester;

(S)-2-({3-[4-(6-Fluoro-benzothiazol-2-ylamino)-phenyl]-N-hydroxy-isoxazole-5-carboximidoyl}-amino)-3-methyl-butyric acid;

(S)-2-({3[4-(6-Fluoro-benzothiazol-2-ylamino)-phenyl]-isoxazole-5-carbonyl}-amino)-3-hydroxy-propionic acid methyl ester;

(S)-2-({3-[4-(6-Fluoro-benzothiazol-2-ylamino)-phenyl]-isoxazole-5-carbonyl}-amino)-3-hydroxy-propionic acid;

(S)-2-{3-[4-(6-Fluoro-benzothiazol-2-ylamino)-phenyl]-isoxazol-5-yl}-4,5-dihydro-thiazole-4-carboxylic acid methyl ester;

(S)-2-({3-[4-(6-Fluoro-benzothiazol-2-ylamino)-phenyl]-isoxazole-5-carbonyl}amino)-3-methoxy-propionic acid methyl ester;

(S)-2-({3-[4-(6-Fluoro-benzothiazol-2-ylamino)-phenyl]-isoxazole-5-carbonyl}-amino)-3-methoxy-propionic acid;

(S)-2-({3-[4-(6-Fluoro-benzothiazol-2-ylamino)-phenyl]-isoxazole-5-carbothioyl}-amino)-3-methoxy-propionic acid methyl ester;

(S)-2-({3-[4-(6-Fluoro-benzothiazol-2-ylamino)-phenyl]-isoxazole-5-carbothioyl}-amino)-3-methoxy-propionic acid;

(S)-2-({3-[4-(6-Fluoro-benzothiazol-2-ylamino)-phenyl]-N-hydroxy-isoxazole-5-carboximidoyl}-amino)-3-methoxy-propionic acid methyl ester;

(S)-2-({3-[4-(6-Fluoro-benzothiazol-2-ylamino)-phenyl]-N-hydroxy-isoxazole-5-carboximidoyl}-amino)-3-methoxy-propionic acid;

(S)-1-{3-[4-(6-Fluoro-benzothiazol-2-ylamino)-phenyl]-isoxazole-5-carbonyl}-pyrrolidine-2-carboxylic acid methyl ester;

(S)-1-{3-[4-(6-Fluoro-benzothiazol-2-ylamino)-phenyl]-isoxazole-5-carbonyl}-pyrrolidine-2-carboxylic acid;

(S)-2-({3-[3-(6-Fluoro-berizothiazol-2-ylamino)-phenyl]-isoxazole-5-carbonyl}-amino)-3-methyl-butyric acid methyl ester;

(S)-2-({3-[3-(6-Fluoro-benzothiazol-2-ylamino)-phenyl]-isoxazole-5-carbonyl}-amino)-3-methyl-butyric acid;

(S)-2-({3-[3-(6-Fluoro-benzothiazol-2-ylamino)-phenyl]-isoxazole-5-carbothioyl}-amino)-3-methyl-butyric acid methyl ester;

(S)-2-({3-[3-(6-Fluoro-benzothiazol-2-ylamino)-phenyl]-isoxazole-5-carbothioyl}-amino)-3-methyl-butyric acid;

(S)-2-({3-[3-(6-Fluoro-benzothiazol-2-ylamino)-phenyl]-N-hydroxy-isoxazole-5-carboximidoyl}-amino)-3-methyl-butyric acid methyl ester;

(S)-2-({3-[3-(6-Fluoro-benzothiazol-2-ylamino)-phenyl]-N-hydroxy-isoxazole-5-carboximidoyl}-amino)-3-methyl-butyric acid;

(S)-2-({3-[3-(6-Fluoro-benzothiazol-2-ylamino)-phenyl]-isoxazole-5-carbonyl}-amino)-3-methoxy-propionic acid methyl ester;

(S)-2-({3-[3-(6-Fluoro-benzothiazol-2-ylamino)-phenyl]isoxazole-5-carbonyl}-amino)-3-methoxy-propionic acid;

(S)-2-({3-[3-(6-Fluoro-benzothiazol-2-ylamino)-phenyl]-isoxazole-5-carbothioyl}-amino)-3-methoxy-propionic acid methyl ester;

(S)-2-({3-[3-(6-Fluoro-benzothiazol-2-ylamino)-phenyl]isoxazole-5-carbothioyl}-amino)-3-methoxy-propionic acid;

(S)-2-({3-[3-(6-Fluoro-benzothiazol-2-ylamino)-phenyl]-N-hydroxy-isoxazole-5-carboximidoyl}-amino)-3-methoxy-propionic acid methyl ester;

(S)-2-({3-[3-(6-Fluoro-benzothiazol-2-ylamino)-phenyl]-N-hydroxy-isoxazole-5-carboximidoyl}-amino)-3-methoxy-propionic acid;

(S)-1-{3-[3-(6-Fluoro-benzothiazol-2-ylamino)-phenyl]-isoxazole-5-carbonyl}-pyrrolidine-2-carboxylic acid methyl ester;

(S)-1-{3-[3-(6-Fluoro-benzothiazol-2-ylamino)-phenyl]-isoxazole-5-carbonyl}-pyrrolidine-2-carboxylic acid;

(S)-1-{3-[3-(6-Fluoro-benzothiazol-2-ylamino)-phenyl]-isoxazole-5-carbothioyl}-pyrrolidine-2-carboxylic acid methyl ester;

(S)-1-{3-[3-(6-Fluoro-benzothiazol-2-ylamino)-phenyl]-isoxazole-5-carbothioyl}-pyrrolidine-2-carboxylic acid;

(R)-2-({3-[4-(6-Fluoro-benzothiazol-2-ylamino)-phenyl]-isoxazole-5-carbonyl}-amino)-3-methyl-butyric acid methyl ester;

(R)-2-({3-[4-(6-Fluoro-benzothiazol-2-ylamino)-phenyl]-isoxazole-5-carbothioyl}-amino)-3-methyl-butyric acid methyl ester;

(R)-2-({3-[4-(6-Fluoro-benzothiazol-2-ylamino)-phenyl]-N-hydroxy-isoxazole-5-carboximidoyl}-amino)-3-methyl-butyric acid methyl ester;

(R)-2-({3-[4-(6-Fluoro-benzothiazol-2-ylamino)-phenyl]-N-hydroxy-isoxazole-5-carboximidoyl}-amino)-3-methyl-butyric acid;

(R)-2-({3-[4-(6-Fluoro-benzothiazol-2-ylamino)-phenyl]-isoxazole-5-carbonyl}-amino)-3-methyl-butyric acid;

(R)-2-({3-[4-(6-Fluoro-benzothiazol-2-ylamino)-phenyl]-isoxazole-5-carbothioy}-amino)-3-methyl-butyric acid;

(S)-2-({3-[4-(6-Fluoro-benzothiazol-2-ylamino)-phenyl]-isoxazole-5-carbonyl}-amino)-3-methyl-butyric acid;

(S)-2-({3-[4-(6-Fluoro-benzothiazol-2-ylamino)-phenyl]-isoxazole-5-carbothioyl}-amino)-3-methyl-butyric acid;

(S)-2-({3-[4-(6-Fluoro-benzothiazol-2-ylamino)-phenyl]-isoxazole-5-carbonyl}-amino)-4-methyl-pentanoic acid methyl ester;

(S)-2-({3-[4-(6-Fluoro-benzothiazol-2-ylamino)-phenyl]-isoxazole-5-carbonyl}-amino)-4-methyl-pentanoic acid;

(S)-2-({3-[4-(6-Fluoro-benzothiazol-2-ylamino)-phenyl]-isoxazole-5-carbothioyl}-amino)-4-methyl-pentanoic acid methyl ester;

(S)-2-({3-[4-(6-Fluoro-benzothiazol-2-ylamino)-phenyl]-isoxazole-5-carbothioyl}-amino)-4-methyl-pentanoic acid;

(S)-2-({3-[4-(6-Fluoro-benzothiazol-2-ylamino)-phenyl]-N-hydroxy-isoxazole-5-carboximidoyl}-amino)-4-methyl-pentanoic acid methyl ester;

(S)-2-({3-[4-(6-Fluoro-benzothiazol-2-ylamino)-phenyl]-N-hydroxy-isoxazole-5-carboximidoyl}-amino)-4-methyl-pentanoic acid;

(S)-({3-[4-(6-Fluoro-benzothiazol-2-ylamino)-phenyl]-isoxazole-5-carbonyl}-amino)-phenyl-acetic acid methyl ester;

(S)-({3-[4-(6-Fluoro-benzothiazol-2-ylamino)-phenyl]-isoxazole-5-carbonyl}-amino)-phenyl-acetic acid;

(S)-({3-[4-(6-Fluoro-benzothiazol-2-ylamino)-phenyl]-isoxazole-5-carbothioyl}amino)-phenyl-acetic acid methyl ester;

(S)-({3-[4-(6-Fluoro-benzothiazol-2-ylamino)-phenyl]-isoxazole-5-carbothioyl}-amino)-phenyl-acetic acid;

(S)-({3-[4-(6-Fluoro-benzothiazol-2-ylamino)-phenyl]-N-hydroxy-isoxazole-5-carboximidoyl}-amino)-phenyl-acetic acid methyl ester;

(S)-({3-[4-(6-Fluoro-benzothiazol-2-ylamino)-phenyl]-N-hydroxy-isoxazole-5-carboximidoyl}-amino)-phenyl-acetic acid;

({3-[4-(6-Fluoro-benzothiazol-2-ylamino)-phenyl]-isoxazole-5-carbonyl}-amino)-acetic acid methyl ester;

({3-[4-(6-Fluoro-benzothiazol-2-ylamino)-phenyl]-isoxazole-5-carbonyl}-amino)-acetic acid;

({3-[4-(6-Fluoro-benzothiazol-2-ylamino)-phenyl]-isoxazole-5-carbothioyl}-amino)-acetic acid methyl ester:

({3-[4-(6-Fluoro-benzothiazol-2-ylamino)-phenyl]-isoxazole-5-carbothioyl}-amino)-acetic acid;

1-({3-[4-(6-Fluoro-benzothiazol-2-ylamino)-phenyl]-isoxazole-5-carbonyl}-amino)-cyclopentanecarboxylic acid methyl ester;

1-({3-[4-(6-Fluoro-benzothiazol-2-ylamino)-phenyl]-isaxazole-5-carbonyl}-amino)-cyclopentanecarboxylic acid;

1-({3-[4-(6-Fluoro-benzothiazol-2-ylamino)-phenyl]-isaxazole-5-carbothioyl}-amino)-cyclopentanecarboxylic acid methyl ester;

1-({3-[4-(6-Fluoro-benzothiazol-2-ylamino)-phenyl]-isoxazole-5-carbothioyl}-amino)-cyclopentanecarboxylic acid;

1-({3-[4-(6-Fluoro-benzothiazol-2-ylamino)-phenyl]-N-hydroxy-isoxazole-5-carboximidoyl}-amino)-cyclopentanecarboxylic acid;

7-{3-[4-(6-Fluoro-benzothiazol-2-ylamino)-phenyl]-isoxazole-5-yl}-9-oxa-6,8-diaza-spiro[4,5]dec-7-en-10-one;

(S)-2-({3-[4-(6-Fluoro-benzothiazol-2-ylamino)-phenyl]-5-phenyl-isoxazole-4-carbonyl}-amino)-3-methyl-butyric acid methyl ester;

(S)-2-({3-[4-(6-Fluoro-benzothiazol-2-ylamino)-phenyl]-5-phenyl-isaxazole-4-carbonyl}-amino)-3-methyl-butyric acid;

(S)-2-({3-[4-(6-Fluoro-benzothiazol-2-ylamino)-phenyl]-5-phenyl-isoxazole-4-carbonyl}-amino)-3-methoxy-propionic acid methyl ester;

(S)-2-({3-[4-(6-Fluoro-benzothiazol-2-ylamino)-phenyl]-5-phenyl-isoxazole-4-carbonyl}-amino)-3-methoxy-propionic acid;

(S)-2-({3-[4-(6-Fluoro-benzothiazol-2-ylamino)-phenyl]-5-phenyl-isoxazole-4-carbothioyl}-amino)-3-methyl-butyric acid methyl ester;

(S)-2-({3-[4-(6-Fluoro-benzothiazol-2-ylamino)-phenyl]-5-phenyl-isoxazole-4-carbothioyl}-amino)-3-methyl-butyric acid;

(S)-2-({3-[4-(6-Fluoro-benzothiazol-2-ylamino)-phenyl]-5-phenyl-isoxazole-4-carbothioyl}-amino)-3-methoxy-propionic acid methyl ester;

(S)-2-({3-[4-(6-Fluoro-benzothiazol-2-ylamino)-phenyl]-5-phenyl-isoxazole-4-carbothioyl}-amino)-3-methoxy-propionic acid;

(S)-3-Methyl-2-({3-[4-(3-phenyl-ureido)-phenyl]-isoxazole-5-carbonyl}-amino)-butyric acid methyl ester;

(S)-3-Methyl-2-({3[4-(3-phenyl-ureido)-phenyl]-isoxazole-5-carbonyl}-amino)-butyric acid;

(S)-3-Methyl-2-({3-[4-(3-phenyl-ureido)-phenyl]-isoxazole-5-carbonyl}-amino)-pentanoic acid methyl ester;

(S)-3-Methyl-2-({3-[4-(3-phenyl-ureido)-phenyl]-isoxazole-5-carbonyl}-amino)-pentanoic acid;

(S)-2-({3-[4-(3-cyclohexyl-ureido)-phenyl]-isoxazole-5-carbonyl}-amino)-3-methyl-butyric acid methyl ester;

(S)-2-({3-[4-(3-cyclohexyl-ureido)-phenyl]-isoxazole-5-carbonyl}-amino-3-methyl-butyric acid;

(S)-2-({3-[4-(3-cyclohexyl-ureido)-phenyl]-isoxazole-5-carbonyl}amino)-4-methyl-pentanoic acid methyl ester;

(S)-2-({3-[4-(3-cyclohexyl-ureido)-phenyl]-isoxazole-5-carbonyl}-amino)-4-methyl-pentanoic acid;

(S)-2-[(3-{4-[3-(4-Fluoro-phenyl)-ureido]-phenyl}-isoxazole-5-carbonyl)-amino]-3-methyl-butyric acid methyl ester:

(S)-2-[(3-{4-[3-(4-Fluoro-phenyl)-ureido]-phenyl}-isoxazole-5-carbonyl)-amino]-3-methyl-butyric acid;

(S)-2-[3-{4-[3-(4-Fluoro-phenyl)-ureido]-phenyl}-isoxazole-5-carbonyl)-amino]-4-methyl-pentanoic acid methyl ester;

(S)-2-[(3-{4-[3-(4-Fluoro-phenyl)-ureido]-phenyl}-isoxazole-5-carbonyl)-amino]-4-methyl-pentanoic acid;

(S)-3-Methyl-2-({4-phenyl-3-[4-(3-phenyl-ureido)-phenyl]-isoxazole-5-carbonyl}-amino)-butyric acid methyl ester;

(S)-3-Methyl-2-({4-phenyl-3-[4-(3-phenyl-ureido)-phenyl]-isoxazole-5-carbonyl}-amino)-butyric acid;

(S)-4-Methyl-2-({4-phenyl-3-[4-(3-phenyl-ureido)-phenyl]-isoxazole-5-carbonyl}-amino)-pentanoic acid methyl ester;

(S)-4-Methyl-2-({4-phenyl-3-[4-(3-phenyl-ureido)-phenyl]-isoxazole-5-carbonyl}-amino)-pentanoic acid;

(S)-2-[(3-{4-[3-(4-Fluoro-phenyl)-ureido]-phenyl}-4-phenyl-isoxazole-5-carbonyl)-amino]-3-methyl-butyric acid methyl ester;

(S)-2-[(3-{4-[3-(4-Fluoro-phenyl)-ureido]-phenyl}-4-phenyl-isoxazole-5-carbonyl)-amino]-3-methyl-butyric acid;

(S)-2-({3-[4-(6-Fluoro-benzothiazol-2-ylamino)-phenyl]-4-phenyl-isoxazole-5-carbonyl}-amino)-4-methyl-pentanoic acid methyl ester;

(S)-2-({3-[4-(6-Fluoro-benzothiazol-2-ylamino)-phenyl]-4-phenyl-isoxazole-5-carbonyl}-amino)-4-methyl-pentanoic acid;

(S)-2-[3-{3-Fluoro-4-[3-(4-fluoro-phenyl)-ureido]-phenyl}-isoxazole-5-carbonyl)-amino]-3-methyl-butyric acid methyl ester;

(S)-2-[3-{3-Fluoro-4-[3-(4-fluoro-phenyl)-ureido]-phenyl}-isoxazole-5-carbonyl)-amino]-3-methyl-butyric acid;

2-(3-(4-(3(2,6-Difluorophenyl)ureido)-3-methylphenyl)isoxazole-5-carboxamido)-3-methylbutanoic acid:

Methyl 2-(3(4-(3-(2,6-difluorophenyl)ureido)-3-methylphenyl)isoxazole-5-carboxamido)-4-methylpentanoate;

2-(3-(4-(3-(2,6-Difluorophenyl)ureido)-3-methylphenyl)isoxazole-5-carboxamido)-4-methylpentanoic acid;

Methyl 2-(3-(4-(3-(2,6-dffluorophenyl)ureido)-3-methylphenyl)isoxazole-5-carboxamido)propanoate;

2-(3-(4-(3-(2,6-Difluorophenyl)ureido)-3-methylphenyl)isoxazole-5-carboxamido)propanoic acid:

2-(3-(4-(3-(2,4-Difluorophenyl)ureido)-3-methylphenyl)isoxazole-5-carboxamido)-3-methylbutanoic acid; and

2-[(3-{4-[3-(2-Fluoro-phenyl)ureido]-phenyl}-isoxazole-5-carbonyl)-amino]-3-methyl-butyric acid methyl ester:

2-(3-(4-(3-(2-Fluorophenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoic acid;

Methyl 2-(3-(4-(3-benzylureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoate;

2-(3-(4-(3-Benzylureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoic acid:

Methyl 2-(3-(4-(3-benzylureido)phenyl)isoxazole-5-carboxamido)-4-methylpentanoate;

2-(3-(4-(3-Benzylureido)phenyl)isoxazole-5-carboxamido)-4-methyl pentanoic acid;

Methyl 2-(3-(4-(3-(2,4-difluorophenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoate;

2-(3-(3-(2,4-Difluorophenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoic acid:

Methyl 2-(3-(4-(3-(2,4-difluorophenyl)ureido)phenyl)isoxazole-5-carboxamido)-4-methylpentanoate;

2-(3-(4-(3-(2,4-Difluorophenyl)ureido)phenyl)isoxazole-5-carboxamido)-4-methylpentanoic acid;

Methyl 2-(3-(4-(3-(4-fluorophenyl)ureido)phenyl)isoxazole-5-carboxamido)propanoate;

2-(3-(4-(3-(4-Fluorophenyl)ureido)phenyl)isoxazole-5-carboxamido)propanoic acid ;

Methyl 2-(3-(4-(3-(4-fluorophenyl)ureido)phenyl)isoxazole-5-carboxamido)-2-methylpropanoate;

2-(3-(4-(3-(4-fluorophenyl)ureido)phenyl)isoxazole-5-carboxamido)-2-methylpropnoic acid;

Methyl 1-(3-(4-(3-(4-fluorophenyl)ureido)phenyl)isoxazole-5-carboxamido)cyclopentanecarboxylate;

1-(3-(4-(3-(4-Fluorophenyl)ureido)phenyl)isoxazole-5-carboxamido)cyelopentanecarboxylic acid:

Methyl 2-methyl-2-(3-(4-(3-phenylureido)phenyl)isoxazole-5-carboxamido)propanoate;

2-methyl-2-(3-(4-(3-phenylureido)phenyl)isoxazole-5-carboxamido) propanoic acid;

Methyl 2-(3-(4-(3-(2,6-difluorophenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoate;

2-(3-(4-(3-(2,6-difluorophenyl)ureido)phenyl)isoxazole-5-carboxamido 3-methylbutanoic acid;

Methyl 3-methyl-2-(3-(4-(3-p-tolylureido)phenyl)isoxazole-5-carboxamido)butanoate;

3-Methyl-2-(3-(4-(3-p-tolylureido)phenyl)isoxazole-5-carboxamido)butanoic acid;

Methyl 2-(3-(4-(3-(4-methoxyphenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoate;

2-(3-(4-(3-(4-methoxyphenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoic acid;

(S)-methyl 2-(3-(4-(3-(3,4-difluorophenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoate;

(S)-2-(3-(4-(3-(3,4-difluorophenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoic acid;

Methyl 2-(3-(5-(3-(4-fluorophenyl)ureido)-2-methylphenyl)isoxazole-5-carboxamido)-4-methylpentanoate;

2-(3-(5-(3-(4-fluorophenyl)ureido)-2-methylphenyl)isoxazole-5-carboxamido)-4-methylpentanoic acid;

Methyl 2-(3-(4-(3-(4-fluorophenyl)ureido)-2-methylphenyl)isoxazole-5-carboxamido)-3-methylbutanoate;

2-(3-(4-(3-(4-fluorophenyl)ureido)-2-methylphenyl)isoxazote-5-carboxamido)-3-methylbutanoic acid;

Methyl 2-(3-(4-(3-(2-fluorophenyl)ureido)-2-methylphenyl)isoxazole-5-carboxamido)-3-methylbutanoate;

2-(3-(4-(3-(2-Fluorophenyl)ureido)-2-methylphenyl)isoxazole-5-carboxamido)-3-methylbutanoic acid;

Methyl 2-(3-(4-(3-(2,4-difluorophenyl)ureido)-2-methylphenyl)isoxazole-5-carboxamido)-3-methylbutanoate;

2-(3-(4-(3-(2,4-difluorophenyl)ureido)-2-methylphenyl)isoxazole-5-carboxamido)-3-methylbutanoic acid;

Methyl 2-(3-(4-(3-(2,4-difluorophenyl)ureido)-2-methylphenyl)isoxazole-5-carboxamido)-4-methylpentanoate;

2-(3-(4-(3-(2,4-difluorophenyl)ureido)-2-methylphenyl)isoxazole-5-carboxamido)-4-methylpentanoic acid;

(S)-Methyl 2-(3-(4-(3-(2,4-Difluorophenyl)ureido)-2-fluorophenyl)isoxazole-5-carboxamido)-3-methylbutanoate;

(S)-2-(3-(4-(3-(2,4-difluorophenyl)ureido)-2-fluorophenyl)isoxazole-5-carboxamido)-3-methylbutanoic acid;

(S)-methyl 2-(3-(2-fluoro-4-(3-(2-fluorophenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoate;

(S)-2-(3-(2-Fluoro-4-(3-(2-fluorophenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoic acid:

(S)-Methyl 2-(3-(2-fluoro-4-(3-(4-fluorophenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoate;

(S)-2-(3-(2-fluoro-4-(3-(4-fluorophenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoic acid;

Methyl 2-(3-(3-fluoro-4-(3-(2-fluorophenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoate;

2-(3-(3-fluoro-4-(3-(2-fluorophenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoic acid;

Methyl 2-(3-(4-(3-(2,4-difluorophenyl)ureido)-3-fluorophenyl)isoxazole-5-carboxamido)-3-ethylbutanoate;

2-(3-(4-(3-(2,4-Difluorophenyl)ureido) 3 fluorophenyl)isoxazole 5 -carboxamido)-3-methylbutanoic acid:

Methyl 2-(3-(4-(3-(3-fluorophenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoate;

2-(3-(4-(3-(3-fluorophenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoic acid;

Methyl 3-methyl-2-(3-(4-(3-o-tolylureido)phenyl)isoxazole-5-carboxamido)butanoate;

3-methyl-2-(3-(4-(3-o-tolylureido)phenyl)isoxazole-5-carboxamido)butanoic acid;

Methyl 2-(3-(4-(3-(2-fluoro-5-methylphenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoate;

2-(3-(4-(3-(2-fluoro-5-methylphenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoic acid;

Methyl 2-(3-(4-(3-(4-butylphenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoate;

2-(3-(4-(3-(4-butylphenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoic acid;

Methyl 2-(3-(4-(3-(3,5-difluorophenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoate;

2-(3-(4-(3 (3,5-difluorophenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoic acid:

Methyl 2-(3-(4-(3-(3-chloro-4-fluorophenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoate;

2-(3-(4-(3-(3-chloro-4-fluorophenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoic acid:

(S)-methyl 3-methyl-2-(3-(4-(3-(2-(trifluoromethyl)phenyl)ureido)phenyl)isoxazole-5-carboxamido)butanoate;

(S)-3-methyl-2-(3-(4-(3-(2-(trifluoromethyl)phenyl)ureido)phenyl)isoxazole-5-carboxamido)butanoic acid;

(S)-Methyl 2-(3-(4-(3-(2,5-dimethoxyphenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoate;

(S)-2-(3-(4-(3-(2,5-Dimethoxyphenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoic acid;

(S)-2-(3-(4-(3-(3,5-difluorophenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoic acid:

(S)-methyl 2-(3-(4-(3-(2,4-dimethoxyphenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoate;

(S)-2-(3-(4-(3-(2,4-dimethoxyphenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoic acid;

(S)-methyl 2-(3-(4-(3-(2,4-dimethylphenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoate;

(S)-2-(3-(4-(3-(2,4-dimethylphenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoic acid;

(S)-methyl 2-(3-(4-(3-(3,4-dimethylphenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoate;

(S)-2-(3-(4-(3-(3,4-dimethylphenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoic acid:

(S)-Methyl 2-(3-(4-(3-(2-chloro-6-methylphenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoatc;

(S)-2-(3-(4-(3-(2-Chloro-6-methylphenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoic acid;

(S)-Methyl 2-(3-(4-(3-benzo[d][1,3]dioxol-5-ylureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoate;

(S)-2-(3-(4-(3-benzo[d][1.3]dioxol-5-ylureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoic acid;

(S)-methyl 2-(3-(4-(3-(4-chlorophenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoate;

(S)-2-(3-(4-(3-(4-Chlorophenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoic acid;

(S)-methyl 2-(3-(4-(3-(2,3-dihydro-1H-inden-5-yl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoate;

(S)-2-(3-(4-(3-(2,3-dihydro-1H-inden-5-yl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoic acid;

(S)-methyl 2-(3-(4-(3-(3-chloro-2-fluorophenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoate;

(S)-2-(3-(4-(3-(3-chloro-2-fluorophenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoic acid;

(S)-methyl 2-(3-(4-(3-(2-methoxyphenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoate;

(S)-2-(3-(4-(3-(2-methoxyphenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoic acid;

(S)-methyl 3-methyl-2-(3-(4-(3-(4-(trifluoromethoxy)phenyl)ureido)phenyl)isoxazole-5-carboxamido)butanoate;

(S)-3-methyl-2-(3-(4-(3-(4-trifluoromethoxy)phenyl)ureido)phenyl)isoxazole-5-carboxamido)butanoic acid;

(S)-methyl 2-(3-(4-(3-(2-chloro-5-methylphenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoate;

(S)-2-(3-(4-(3-(2-chloro-5-methylphenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoic acid;

(S)-Methyl 3-methyl-2-(3-(4-(3-(2,3,4-trifluorophenyl)ureido)pbenyl)isoxazole-5-carboxamido)butanoate;

(S)-3-Methyl-2-(3-(4-(3-(2,3,4-trifluorophenyl)ureido)phenyl)isoxazole-5-carboxamido)butanoic acid;

(S)-methyl 2-(3-(4-(3-(4-chloro-2-fluorophenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoate;

(S)-2-(3-(4-(3-(4-chloro-2-fluorophenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoic acid;

(S)-methyl 2-(3-(4-(3-(5-chloro-2-methylphenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoate;

(S)-2-(3-(4-(3-(5-chloro-2-methylphenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoic acid;

(S)-Methyl 3-methyl-2-(3-(4-(3-(4-(methylthio)phenyl)ureido)phenyl)isoxazole-5-carboxamido)butanoate;

(S)-3-methyl-2-(3-(4-(3-(4-(methylthio)phenyl)ureido)phenyl)isoxazole-5-carboxamido)butanoic acid;

(S)-methyl 2-(3 -(4(3 -(2,5 -difluorophenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoate;

(S)-2-(3-(4-(3-(2,5-difluorophenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoic acid;

(S)-methyl 2-(3-(4-(3-(4-chloro-2-phenoxyphenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoate;

(S)-2-(3-(4-(3-(4-chloro-2-phenoxyphenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoic acid;

(S)-methyl 3-methyl-2-(3-(4-(3-(2-(trifluoromethoxy)phenyl)ureido)phenyl)isoxazole-5-carboxamido)butanoate;

(S)-3-methyl-2-(3-(4-(3-(2-(trifluoromethoxy)phenyl)ureido)phenyl)isoxazole-5-carboxamido)butanoic acid;

(S)-methyl 2-(3-(4-(3-(3,5-dimethylphenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoate;

(S)-2-(3-(4-(3-(3,5-dimethylphenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoic acid;

(S)-methyl 2-(3-(4-(3-(6-chloropyridin-3-yl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoate;

(S)-2-(3-(4-(3-(6-chloropyridin-3-yl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoic acid;

(S)-methyl 2-(3-(4-(3-(3-chlorophenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoate;

(S)-2-(3-(4-(3-(3-chlorphenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoic acid;

(S)-methyl 2-(3-(4-(3-(2-chloro-5-(trifluoromethyl)phenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoate;

(S)-2-(3-(4-(3-(2-chloro-5-(trifluoromethyl)phenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoic acid;

(S)-Methyl 2-(3-(4-(3-(4-fluoro-2-(trifluoromethyl)phenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoate;

(S)-2-(3-(4-(3-(4-fluoro-2-(trifluoromethyl)phenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoic acid;

(S)-methyl 2-(3-(4-(3-(4-chloro-2-(trifluoromethyl)phenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoate;

(S)-2-(3-(4-(3-(4-chloro-2-(trifluoromethyl)phenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoic acid;

(R)-methyl 2-(3-(4-(3-(2-cyanophenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoate;

(R)-2-(3-(4-(3-(3-cyanophenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoic acid;

(R)-methyl 2-(3-(4-(3-(4-cyanophenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoate;

(R)-2-(3-(4-(3-(4-Cyanophenyl)ureido)phenyl)isoxazole-5-carboxamido-3-methylbutanoic acid;

(R)-Methyl 2-(3-(4-(3-(2-chlorophenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoate;

(R)-2-(3-(4-(3-(2-Chlorophenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoic acid;

(R)-Methyl 2-(3-(4-(3-(2-fluorophenyl)ureido)phenyl)isoxazole-5-carbothioamido)-3-methylbutanoate;

(R)-Methyl 3-methyl-2-(3-(4-(3-p-tolylureido)phenyl)isoxazole-5-carbothioamido) butanoate;

(R,Z)-Methyl 2-(ethylthio(3-(4-(3-(2-fluorophenyl)ureido)phenyl)isoxazol-5-yl)methyleneamino)-3-methylbutanoate;

(R,Z)-Methyl 2-(ethylthio(3-(4-(3-p-tolylureido)phenyl)isoxazol-5- methyleneamimo)-3-methylbutanoate;

(R,E)-2-(3-(4-(3-(2-Fluorophenyl)ureido)phenyl)-N′-hydroxyisoxazole-5-caboximidamido)-3-methylbutanoic acid;

(S)-Methyl 2-(3-(4-(3-(4-isopropylphenyl)ureido)phenyl)isoxazole-5-carboxamide)-3-methylbutanoate;

(S)-2-(3-(4-(3-(4-Isopropylphenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoic acid;

(S)-Methyl 2-(3-(4-(3-(2-fluoro-6-(trifluoromethyl)phenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoate;

(S)-2-(3-(4-(3-(2-Fluoro-6-(trifluoromethyl)phenyl)ureido)phenyl)ismazole-5-carboxamido)-3-methylbutanoic acid;

(S)-Methyl 2-(3-(4-(3-(2-chloro-4-(trifluoromethyl)phenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoate;

(S)-2-(3-(4-(3-(2-Chloro-4-(trifluoromethyl)phenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoic acid;

(S)-Methyl 2-(3-(4-(3-(2-chloro-6-(trifluoromethyl)phenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoate;

(S)-2-(3-(4-(3-(2-Chloro-6-(trifluoromethyl)phenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoic acid;

(S)-Methyl 2-(3-(4-(3-(5-chloro-2-phenoxyphenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoate;

(S)-2-(3-(4-(3-(5-Chloro-2-phenoxyphenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoic acid;

(S)-Methyl 3-methyl-2-(3-(4-(3-(2-phenoxyphenyl)ureido)phenyl)isoxazole-5-carboxamido)butanoate;

(S)-3-Methyl-2-(3-(4-(3-(2-phenoxyphenyl)ureido)phenyl)isoxazole-5-carboxamido)butanoic acid;

(S)-Methyl 3-methyl-2-(3-(4-(3(4-phenoxyphenyl)ureido)phenyl)isoxazole-5-carboxamido)butanoate;

(S)-3-Methyl-2-(3-(4-(3-(4-phenoxyphenyl)ureido)phenyl)isoxazole-5-carboxamido)butanoic acid;

Methyl 2-(3-(3-(4-(3-(2-fluorophenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-phenyl propanoate;

2-(3-(4-(3-(2-Fluorophenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-phenylpropanoic acid;

Methyl 3-phenyl-2-(3-(4-(3-p-tolylureido)phenyl)isoxazole-5-carboxamido)propanoate;

3-Phenyl-2-(3-(4-(3-p-tolylureido)phenyl)isoxazole-5-carboxamido)propanoic acid;

Methyl 2-(3-(4-(3-(2,4-difluorophenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-phenylpropanoate;

2-(3-(4-(3-(2,4-Difuorophenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-phenylpropanoic acid;

Methyl 2-(3-(4-(3-(3-chloro4-methylphenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoate;

2-(3-(4-(3-(3-Chloro-4-methylphenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoic acid;

Ethyl 2-(3-(4-(3-(3-fluoro-4-methylphenyl)ureido)phenyl)isoxazole-5-carboxamido-3-methylbutanoate;

2-(3-(4-(3-(3-Fluoro-4-methylphenyl)ureido)phenyl)pisoxazole-5-carboxamido)-3-methylbutanoic acid;

Methyl 2-(3-(4-(3-(5-fluoro-2-methylphenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoate;

2-(3-(4-(3-(5-Fluoro-2-methylphenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoic acid;

Methyl 4-(3-(4-(3-(2-fluorophenyl)ureido)phenyl)isoxazole-5-carboxamido)butanoate;

4-(3-(4-(3-(2-Fluorophenyl)ureido)phenyl)isoxazole-5-carboxamido)butanoic acid;

Methyl 4-(3-(4-(3-p-tolylureido)phenyl)isoxazole-5-carboxamido)butanoate;

4-(3-(4-(3-p-Tolylureido)phenyl)isoxazole-5-carboxamido)butanoic acid;

(R)-Methyl 2-(3-(4-(3-(2-fluorophenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoate;

(R)-2-(3-(4-(3-(2-Fluorophenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoic acid;

(R)-Methyl 1-(3-(4-(3-(2-fluorophenyl)ureido)phenyl)isoxazole-5-carbonyl)pyrrolidine-2-carboxylate;

(R)-1-(3-(4-(3-(2-Fluorophenyl)ureido)phenyl)isoxazole-5-carbonyl)pyrrolidine-2-carboxylic acid;

(S)-Methyl 1-(3-(4-(3-(2-fluorophenyl)ureido)phenyl)isoxazole-5-carbonyl)pyrrolidine-2-carboxylate;

(S)-1-(3-(4-(3-(2-Fluorophenyl)ureido)phenyl)isoxazole-5-carbonyl)pyrrolidine-2-carboxylic acid;

Methyl 3-methyl-2-(3-(4-(3-(o-tolylsultbnyl)ureido)phenyl)isoxazole-5-carboxamido)butanoate;

3-Methyl-2-(3-(4-(3-(o-tolylsulfonyl)ureido)phenyl)isoxazole-5-carboxamido)butanoic acid;

(S)-Methyl 3-methyl-2-(3-(4-(3-m-tolylureido)phenyl)isoxazole-5-carboxamido)butanoate;

(S)-3-Methyl-2-(3-(4-(3-m-tolylureido)phenyl)isoxazole-5-carboxamido)butanoic acid;

(S)-methyl 2-(3-(4-(3-(3-fluorophenyl)thioureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoate;

(S)-2-(3-(4-(3-(3-Fluorophenyl)thioureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoic acid;

(S)-Methyl 2-(3-(4-(3-(2-fluorophenyl)thioureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoate;

(S)-2-(3-(4-(3-(2-Fluorophenyl)thioureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoic acid;

(S)-Methyl 3-methyl-2-(3-(4-(3-p-tolylthioureido)phenyl)isoxazole-5-carboxamido)butanoate;

(S)-Methyl 3-(4-hydroxyphenyl)-2-(3-(4-(3-p-tolylureido)phenyl)isoxazole-5-carboxamido)propanoate;

(S)-3-(4-Hydroxyphenyl)-2-(3-(4-(3-p-tolylureido)phenyl)isoxazole-5-carboxamido)propanoic acid;

(S)-Methyl 2-(3-(4-(3-(2-fluorophenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-(4-hydroxyphenyl)propanoate;

Methyl 3-methyl-2-(3-(4-(3-(4-(trifluoromethyl)phenyl)ureido)phenyl)isoxazole-5-carboxamido)butanoate;

3-Methyl-2-(3-(4-(3-(4-(trifluoromethyl)phenyl)ureido)phenyl)isoxazole-5-carboxamido)butanoie acid;

Methyl 3-methyl-2-(3-(4-(3-(3-(trifluoromethyl)phenyl)ureido)phenyl)isoxazole-5-carboxamido)butanoate;

3-Methyl-2-(3-(4-(3-(3-(trifluoromethyl)phenyl)ureido)phenyl)isaxazole-5-carboxamido)butanoic acid;

Methyl 3-methyl-2-(3-(4-(3-pyridin-2-ylureido)phenyl)isoxazole-5-carboxamido)butanoate;

3-methyl-2-(3-(4-(3-pyridin-2-ylureido)phenyl)isoxazole-5-carboxamido)butanoic acid;

2-({3-[4-(3-{4-[5-(1-Methoxycarbonyl-2-methy-propylcarbamoyl)-isoxazol-3-yl]-phenyl}-ureido)-phenyl]-isoxazol-5-carbonyl}-amino)-3-methyl-butyric acid methyl ester;

2-({3-[4-(3-{4-[5-(1-Carboxy-2-methyl-propylcarbamoyl)-isoxazol-3-yl]-phenyl}-ureido)-phenyl]-isoxazol-5-carbonyl}-amino)-3-methyl-butyric acid;

Methyl 4-(3-(4-(5-(1-methoxy-3-methyl-1-oxobutan-2-ylcarbamoyl)isoxazol-3-yl)phenyl)ureido)benzoate;

Methyl 2-(3-(4-(3-(4-fluoro-2-methylphenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoate;

2-(3-(4-(3-(4-fluoro-2-methylphenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoic acid;

Methyl 2-(3-(4-(3-(2-chloro-4-(trifluoromehoxy)phenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoate;

2-(3-(4-(3-(2-chloro-4-(trifluoromethoxy)phenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoic acid;

Ethyl 2-(3-(4-(3-(3-chloro-4-(trifluoromethoxy)phenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoate;

(3-(4-(3-(3-chloro-4-(trifluoromethoxy)phenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoic acid;

Methyl 2-(3-(4-(3-biphenyl-2-ylureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoate;

2-(3-(4-(3-biphenyl-2-ylureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoic acid;

Methyl 2-(3-(4-(3-(4-cyclohexylphenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoate;

2-(3-(4-(3-(4-cyclohexylphenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoic acid;

Methyl 3-methyl-2-(3-(4-(3-(2-methyl-4-(trifluoromethoxy)phenyl)ureido)phenyl)isoxazole-5-carboxamido)butanoate;

3-methyl-2-(3-(4-(3-(2-methyl-4-(trifluoromethoxy)phenyl)ureido)phenyl)isoxazole-5-carboxamido)butanoic acid;

Methyl 2-(3-(4-(4-tert-butylbenzamido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoate;

2-(3-(4-(4-tert-butylbenzamido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoic acid;

(S)-Methyl 2-(3-(4-(3-(2-fluorophenyl)ureido)phenyl)isoxazole-5-carbamido)-3-hydroxypropanoate;

(S)-2-(3-(4-(3-(2-Fluorophenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-hydroxypropanoic acid;

(S)-tert-butyl 2-(3-(4-(3-(2-fluorophenyl)ureido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoate;

Methyl 2-(3-(4-(3-(2-fluorophenyl)ureido)phenyl)isoxazole-5-carboxamido)acrylate;

2-(3-(4-(3-(2-Fluorophenyl)ureido)phenyl)isoxazole-5-carboxamido)acrylic acid;

Methyl 2-(3-(4-(3-p-tolylureido)phenyl)isoxazole-5-carboxamido)acrylate;

2-(3-(4-(3-p-tolylureido)phenyl)isoxazole-5-carboxamido)acrylic acid;

(S)-Methyl 2-(3-(4-(3-(2-fluorophenyl)ureido)phenyl)-N-methylisoxazole-5-carboxamido)-3-methylbutanoate;

(S)-2-(3-(4-(3-(2-fluorophenyl)ureido)phenyl)-N-methylisoxazole-5-carboxamido)-3-methylbutanoic acid;

(S)-methyl 2-(3-(4-(3-(4-fluorophenyl)ureido)phenyl)-N-methylisoxazole-5-carboxamido-3-methylbutanoate;

(S)-2-(3-(4-(3-(4-fluorophenyl)ureido)phenyl)-N-methylisoxazole-5-carboxamido)-3-methylbutanoic acid;

(S)-Methyl 3-methyl-2-(N-methyl-3-(4-(3-(3-(trifluoromethyl)phenyl)ureido)phenyl)isoxazole-5-carboxamido)butanoate;

(S)-3-methyl-2-(N-methyl-3-(4-(3-(3-(trifluoromethyl)phenyl)ureido)phenyl)isoxazole-5-carboxamido)butanoic acid;

(S)-methyl 2-(3-(4-(3-cyclohexylureido)phenyl)-N-methylisoxazole-5-carboxamido)-3-methylbutanoate;

(S)-2-(3-(4-(3-cyclohexylureido)phenyl)-N-methylisoxazole-5-carboxamido)-3-methylbutanoic acid;

(S)-methyl 2-(3-(4-(3-(2-chlorophenyl)ureido)phenyl)-N-mcthylisoxazole-5-carboxamido)-3-methylbutanoate;

(S)-2-(3-(4-(3-(2-chlorophenyl)ureido)phenyl)-N-methylisoxazole-5-carboxamido)-3-methylbutanoic acid:

(R)-methyl 2-(3-(4-(2-fluorophenylsulfonamido)phenyl)isoxazole-5-carboxamido)-3-Methylbutanoate;

(R)-Methyl 2-(3-(4-(2,6-difluorophenylsulfonamido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoate;

(R)-Methyl 3-methyl-2-(3-(4-(4-(trifluoromethyl)phenylsulfonamido)phenyl)isoxazole-5-carboxamido)butanoate;

(R)-3-Methyl-2-(3-(4-(4-(trifluoromethyl)phenylsulfonamido)phenyl)isoxazole-5-carboxamido)butanoic acid;

(R)-2-(3 -(4-(2,6-Difluorophenylsulfonamido)phenyl)isoxazole-5-carboxamido)-3-methyibutanoic acid;

(R)-2-(3-(4-(3,5-Difluorophenylsulfonamido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoic acid;

Methyl 2-(3-(4-(benzyloxy)phenyl)isoxazole-5-carboxamido)-3-methylbutanoate;

2-(3-(4-(Benzyloxy)phenyl)isoxazole-5-carboxamido)-3-methylbutanoic acid;

Methyl 2-(3-(4-(4-fluorobenzyloxy)phenyl)isoxazole-5-carboxamido)-3-methylbutanoate;

2-(3-(4-(Benzyloxy)phenyl)isoxazole-5-carboxamido)-3-methylbutanoic acid;

Methyl 3-methyl-2-(3-(4-(3-(trifluoromethyl)benzyloxy)phenyl)isoxazole-5-carboxamido)butanoate;

3-Methyl-2-(3-(4-(3-(trifluoromethyl)benzyloxy)phenyl)isoxazole-5-carboxamido)butanoic acid;

Methyl 3-methyl-2-(3-(4-(4-(trifluoromethyl)benzyloxy)phenyl)isoxazole-5-carboxamido)butanoate;

3-methyl-2-(3-(4-(4-(trifluoromethyl)benzyloxy)phenyl)isoxazole-5-carboxamido)butanoic acid;

Methyl 3-methyl-2-(3-(4-(2-(trifluoromethyl)benzyloxy)phenyl)isoxazole-5-carboxamido)butanoate;

3-methyl-2-(3-(4-(2-(trifluoromethyl)benzyloxy)phenyl)isoxazole-5-carboxamido)butanoic acid;

Methyl 2-(3-(4-(2,4-difluorobenzyloxy)phenyl)isoxazole-5-carboxamido)-3-methylbutanoate;

2-(3-(4-(2,4-Difluorobenzyloxy)phenyl)isoxazole-5-carboxamido)-3-methylbutanoic acid;

Methyl 1-(3-(4-(benzyloxy)phenyl)isoxazole-5-carbonyl)pyrrolidine-2-carboxylate;

Methyl 2-(3-(4-(6-fluorobenzo[d]thiazol-2-yloxy)phenyl)isoxazole-5-carboxamido)-3-methylbutanoate;

2-(3-(4-(6-fluorobenzo[d]thiazol-2-yloxy)phenyl)isoxazole-5-carboxamido)-3-methylbutanoic acid;

Methyl 3-methyl-2-(3-(4-(2-oxo-2-(3-(trifluoromethyl)phenylamino)acetamido)phenyl)isoxazole-5-carboxamido)butanoate;

3-Methyl-2-(3-(4-(2-oxo-2-(3-(trifluoromethyl)phenylamino)acetamido)phenyl)isoxazole-5-carboxamido)butanoic acid;

Methyl 2-(3-(4-(2-(2,4-difluorophenylamino)-2-oxoacetamido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoate;

2-(3-(4-(2-(2,4-difluorophenylamino)-2-oxoacetamido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoic acid;

Methyl 2-(3-(4-((R)-2-hydroxy-2-phenylacetamido)phenyl)isoxazole-5-carboxamido)-3-methylbutanoate;

2-(3-(4-((R)-2-hydroxy-2-phenylacetamido)phenyl)isoxazole-5-carboxamido)-3-methyl butanoic acid; or

a stereoisomer, a tautomer or a pharmaceutically acceptable salt thereof.

11. A pharmaceutical composition, comprising a therapeutically effective amount of a compound of formula (I) according to claim 1 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient or carrier.

12. A method for the treatment of diseases mediated by DGAT-1, comprising administering to a mammal in need thereof a therapeutically effective amount of a compound of formula (I) according to claim 1 or a pharmaceutically acceptable salt or a pharmaceutically acceptable solvate thereof.

13. A process for the preparation of a compound of formula (Ivi),

which comprises,

reacting a compound of formula (Iv)

 with a compound of formula R Z NH—R B —COOR 9 in a solvent such as dimethyl formamide and in presence of a base such as triethylamine and a coupling agent such as N-Hydroxybenzotriazole and N,N′-dicyclohexylcarbodiimide, wherein Y 1 is selected from

 R A , L 1 , R X , R Y , R Z , R B , R 9 and p are as defined for formula (I) according to claims 1 , T is —O— or —S— and * indicates point of attachment to phenyl ring;

optionally, converting the resulting compound into a pharmaceutically acceptable salt.

14. A process for the preparation of a compound of formula (Ixix)

which comprises

reacting a compound of formula (Ixviii)

 with a compound of formula R A —N═C═O or with a compound of formula R A —NH 2 in presence of a coupling agent such as carbonyl diimidazole, wherein R A , R X , R Z , R B , R 9 , and p are as defined for formula (I) according to claim 1 and Y 1 is selected from

 wherein R Y is as defined for formula (I) in claim 1 and * indicates point of attachment to phenyl ring;

optionally, converting the resulting compound into a pharmaceutically acceptable salt.

15. A process for the preparation of a compound of formula (Iiii)

which comprises,

reacting a compound formula 2a

 i) with a compound of formula R A (CR 4 R 5 ) b -L g or ii) by reductive alkylation of a compound of formula (2a) using a compound of formula R A (CR 4 R 5 ) b-1 —CHO, wherein R A , L 1 , R X and p are as defined for formula (I) according to claim 1 ; R p is a suitable protecting group selected from methyl, ethyl, tert-butyl, benzyl, p-methoxybenzyl and Y 1 is selected from

 wherein R Y is as defined for formula (I) in claim 1 and * indicates point of attachment to phenyl ring.

Assignments (3)
CHANGE OF NAME Recorded Nov 21, 2012
From: PIRAMAL HEALTHCARE LIMITED
To: PIRAMAL ENTERPRISES LIMITED
Reel/Frame 029337/0729 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 20, 2012
From: PIRAMAL LIFE SCIENCES LIMITED
To: PIRAMAL HEALTHCARE LIMITED
Reel/Frame 028599/0103 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 26, 2011
From: GANGOPADHYAY, ASHOK KUMAR; KADAM, KISHORKUMAR SHIVAJIRAO; JADHAV, RAVINDRA DNYANDEV; MISTRY, HITESH; SHARMA, RAJIV
To: PIRAMAL LIFE SCIENCES LTD
Reel/Frame 026179/0662 →