Diacylglycerol Acyltransferase Inhibitors

• US 20090105273A1
• Filed: 05/01/2008
• Published: 04/23/2009
• Est. Priority Date: 05/22/2007
• Status: Active Grant

• Current Assignee: Madrigal Pharmaceuticals, Inc.
• Original Assignee: Madrigal Pharmaceuticals, Inc.
• Inventors: McDermott, Lee Aopstle, Yun, Weiya, Hamilton, Matthew Michael, Qian, Yimin, Bolin, David Robert, Firooznia, Fariborz, Tan, Jenny, Cheung, Adrian Wai-Hing
• Granted Patent: US 8,153,644 B2
• Time in Patent Office: Days
• US Class Current: 514/254.20
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: C07D 231/14 with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
• CPC Class Codes: C07D 249/06 with aryl radicals directly attached to ring atoms
• CPC Class Codes: C07D 263/34 with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
• CPC Class Codes: C07D 277/56 Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
• CPC Class Codes: C07D 307/68 Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
• CPC Class Codes: C07D 401/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 401/14 containing three or more hetero rings
• CPC Class Codes: C07D 403/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 405/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 409/14 containing three or more hetero rings
• CPC Class Codes: C07D 413/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 413/14 containing three or more hetero rings
• CPC Class Codes: C07D 417/14 containing three or more hetero rings

Abstract

Provided herein are compounds of the formula (I):

as well as pharmaceutically acceptable salts thereof, wherein the substituents are as those disclosed in the specification. These compounds, and the pharmaceutical compositions containing them, are useful for the treatment of diseases such as, for example, obesity, type II diabetes mellitus and metabolic syndrome.

Claims

1. A compound of formula (I):

wherein;

R₁ is phenyl or 5- or 6-membered heteroaryl, said phenyl and heteroaryl being unsubstituted or substituted with halogen, lower alkyl, alkoxy or O—

CF₃;

R₂ is halogen, lower alkyl, haloloweralkyl or alkoxy;

R₃ is nitrogen, oxygen or absent, said nitrogen being unsubstituted or substituted with lower alkyl;

R₄ is carbon, nitrogen, oxygen or absent, said carbon or nitrogen being unsubstituted or substituted with lower alkyl,

wherein both R₃ and R₄ are not absent;

R₅ is -loweralkyl,

-alkoxy,

-hydroxy,

-amine,

-lower alkyl amine,

-haloloweralkyl,

-lower alkoxy,

-lower alkenyloxy,

-cycloloweralkyl, unsubstituted or substituted with one to four substituents from lower

alkyl, hydroxy, halogen, —

C(O)OH, —

C(O)O-lower alkyl or —

C(O)O-lower alkyl-phenyl,

-5- or 6-membered heterocycloalkyl, unsubstituted or substituted, with one to four substituents from lower alkyl, hydroxy, halogen, —

SO₂-loweralkyl, —

C(O)OH, —

C(O)O-lower alkyl or —

C(O)O-lower alkyl-phenyl,

-5- or 6-membered aryl, unsubstituted or substituted with one to four substituents from lower alkyl, hydroxy, halogen, —

C(O)OH, —

C(O)O-lower alkyl or —

C(O)O-lower alkyl-phenyl,

-5- or 6-membered heteroaryl, unsubstituted or substituted with one to four substituents from lower alkyl, hydroxy, halogen, —

C(O)OH, C(O)O-lower alkyl or —

C(O)O-lower alkyl-phenyl,

—

(CH₂)_nC(O)OH,

—

CH₂C(lower alkyl)₂C(O)OH,

—

CH₂(cycloalkyl)C(O)OH,

-(cycloalkyl)C(O)OH,

—

CH₂C(CH₃)₃,

—

(CH₂)_n-cycloalkyl,

-cycloalkenyl,

-bicycloalkenyl-C(O)OH,

—

(CH₂)_n—

O-alkyl,

—

O—

C(═

C)-lower alkyl,

—

O—

(CH₂)_n-phenyl,

—

NSO₂-loweralkyl,

—

NSO₂-cycloalkyl,

—

NSO₂-aryl,

—

N-lower alkyl,

—

N-cycloalkyl, said cycloalkyl being unsubstituted or substituted with —

C(O)OH,

—

N-heterocycloalkyl,

—

N-aryl,

—

N—

(CH₂)_n-aryl,

—

N-heteroaryl, said heteroaryl being unsubstituted or substituted with alkyl,

—

N—

CH(lower alkyl)C(O)OH,

—

N-(cycloalkyl)C(O)OH,

—

N—

CH(lower alkyl)C(O)O-lower alkyl,

-phenyl-C(O)OH,

X is 5- or 6-membered aryl or 5- or 6-membered heteroaryl, said aryl or heteroaryl being unsubstituted or substituted with lower alkyl, halogen or cyano;

Y is phenyl, heteroaryl, cycloloweralkyl, or 5- or 6-membered heterocycloalkyl, —

N(CH₂)_n)N—

, said phenyl, cycloloweralkyl or heterocycloalkyl being unsubstituted or substituted with lower alkyl, halogen or cyano; and

n is 1, 2 or 3,

or pharmaceutically acceptable salts thereof,

2. The compound according to claim 1, wherein:

R₁ is phenyl, unsubstituted or substituted with halogen, lower alkyl, alkoxy or O—

CF₃;

R₂ is halogen, lower alkyl, haloloweralkyl or alkoxy;

R₃ is nitrogen, oxygen or absent, said nitrogen being unsubstituted or substituted with lower alkyl;

R₄ is carbon, nitrogen, oxygen or absent, said carbon or nitrogen being unsubstituted or substituted with lower alkyl;

wherein both R₃ and R₄ are not absent;

R₅ is -loweralkyl,

-alkoxy,

-hydroxy,

-amine,

-lower alkyl amine,

-haloloweralkyl,

-lower alkoxy,

-lower alkenyloxy,

-cycloloweralkyl, unsubstituted or substituted with one to four substituents from lower

alkyl, hydroxy, halogen, —

C(O)OH, —

C(O)O-lower alkyl or —

C(O)O-lower alkyl-phenyl,

-5- or 6-membered heterocycloalkyl, unsubstituted or substituted, with one to four substituents from lower alkyl, hydroxy, halogen, —

SO₂-loweralkyl, —

C(O)OH, —

C(O)O-lower alkyl or —

C(O)O-lower alkyl-phenyl,

-5- or 6-membered aryl, unsubstituted or substituted with one to four substituents from

lower alkyl, hydroxy, halogen, —

C(O)OH, —

C(O)O-lower alkyl or —

C(O)O-lower alkyl-phenyl,

-5- or 6-membered heteroaryl, unsubstituted or substituted with one to four substituents from lower alkyl, hydroxy, halogen, —

C(O)OH, C(O)O-lower alkyl or —

C(O)O-lower alkyl-phenyl,

—

(CH₂)_nC(O)OH,

—

CH₂C(lower alkyl)₂C(O)OH,

—

CH₂(cycloalkyl)C(O)OH,

-(cycloalkyl)C(O)OH,

—

CH₂C(CH₃)₃,

—

(CH₂)_n-cycloalkyl,

-cycloalkenyl,

-bicycloalkenyl-C(O)OH,

—

(CH₂)_n—

O-alkyl,

—

O—

C(═

C)-lower alkyl,

—

O—

(CH₂)_n-phenyl,

—

NSO₂-loweralkyl,

—

NSO₂-cycloalkyl,

—

NSO₂-aryl,

—

N-lower alkyl,

—

N-cycloalkyl, said cycloalkyl being unsubstituted or substituted with —

C(O)OH,

—

N-heterocycloalkyl,

—

N-aryl,

—

N—

(CH₂)_n-aryl,

—

N-heteroaryl, said heteroaryl being unsubstituted or substituted with alkyl,

—

N—

CH(lower alkyl)C(O)OH,

—

N-(cycloalkyl)C(O)OH,

—

N—

CH(lower alkyl)C(O)O-lower alkyl,

-phenyl-C(O)OH,

X is 5- or 6-membered aryl or 5- or 6-membered heteroaryl, said aryl or heteroaryl being unsubstituted or substituted with lower alkyl, halogen or cyano;

Y is phenyl, heteroaryl, cycloloweralkyl, or 5- or 6-membered heterocycloalkyl, —

N(CH₂)_n)N—

, said phenyl, cycloloweralkyl or heterocycloalkyl being unsubstituted or substituted with lower alkyl, halogen or cyano;

n is 1, 2 or 3.

3. The compound according to claim 1, wherein:

R₁ is 5- or 6-membered heteroaryl unsubstituted or substituted with halogen, lower alkyl, alkoxy or O—

CF₃;

R₂ is halogen, lower alkyl, haloloweralkyl or alkoxy;

R₃ is nitrogen, oxygen or absent, said nitrogen being unsubstituted or substituted with lower alkyl;

R₄ is carbon, nitrogen, oxygen or absent, said carbon or nitrogen being unsubstituted or substituted with lower alkyl;

wherein both R₃ and R₄ are not absent;

R₅ is -loweralkyl,

-alkoxy,

-hydroxy,

-amine,

-lower alkyl amine,

-haloloweralkyl,

-lower alkoxy,

-lower alkenyloxy,

-cycloloweralkyl, unsubstituted or substituted with one to four substituents from lower

alkyl, hydroxy, halogen, —

C(O)OH, —

C(O)O-lower alkyl or —

C(O)O-lower alkyl-phenyl,

-5- or 6-membered heterocycloalkyl, unsubstituted or substituted, with one to four substituents from lower alkyl, hydroxy, halogen, —

SO₂-loweralkyl, —

C(O)OH, —

C(O)O-lower alkyl or —

C(O)O-lower alkyl-phenyl,

-5- or 6-membered aryl, unsubstituted or substituted with one to four substituents from

lower alkyl, hydroxy, halogen, —

C(O)OH, —

C(O)O-lower alkyl or —

C(O)O-lower alkyl-phenyl,

-5- or 6-membered heteroaryl, unsubstituted or substituted with one to four substituents from lower alkyl, hydroxy, halogen, —

C(O)OH, C(O)O-lower alkyl or —

C(O)O-lower alkyl-phenyl,

—

(CH₂)_nC(O)OH,

—

CH₂C(lower alkyl)₂C(O)OH,

—

CH₂(cycloalkyl)C(O)OH,

-(cycloalkyl)C(O)OH,

—

CH₂C(CH₃)₃,

—

(CH₂)_n-cycloalkyl,

-cycloalkenyl,

-bicycloalkenyl-C(O)OH,

—

(CH₂)_n—

O-alkyl,

—

O—

C(═

C)-lower alkyl,

—

O—

(CH₂)_n-phenyl,

—

NSO₂-loweralkyl,

—

NSO₂-cycloalkyl,

—

NSO₂-aryl,

—

N-lower alkyl,

—

N-cycloalkyl, said cycloalkyl being unsubstituted or substituted with —

C(O)OH,

—

N-heterocycloalkyl,

—

N-aryl,

—

N—

(CH₂)_n-aryl,

—

N-heteroaryl, said heteroaryl being unsubstituted or substituted with alkyl,

—

N—

CH(lower alkyl)C(O)OH,

—

N-(cycloalkyl)C(O)OH,

—

N—

CH(lower alkyl)C(O)O-lower alkyl,

-phenyl-C(O)OH,

X is 5- or 6-membered aryl or 5- or 6-membered heteroaryl, said aryl or heteroaryl being unsubstituted or substituted with lower alkyl, halogen or cyano;

Y is phenyl, heteroaryl, cycloloweralkyl, or 5- or 6-membered heterocycloalkyl, —

N(CH₂)_n)N—

, said phenyl, cycloloweralkyl or heterocycloalkyl being unsubstituted or substituted with lower alkyl, halogen or cyano;

n is 1, 2 or 3.

4. The compound according to claim 1, wherein:

R₁ is phenyl or 5- or 6-membered heteroaryl, said phenyl and heteroaryl being unsubstituted or substituted with halogen, lower alkyl, alkoxy or O—

CF₃;

R₂ is halogen, lower alkyl, haloloweralkyl or alkoxy;

R₃ is nitrogen, oxygen or absent, said nitrogen being unsubstituted or substituted with lower alkyl;

R₄ is carbon, nitrogen, oxygen or absent, said carbon or nitrogen being unsubstituted or substituted with lower alkyl;

wherein both R₃ and R₄ are not absent;

R₅ is -loweralkyl,

-alkoxy,

-hydroxy,

-amine,

-lower alkyl amine,

-haloloweralkyl,

-lower alkoxy,

-lower alkenyloxy,

-cycloloweralkyl, unsubstituted or substituted with one to four substituents from lower

alkyl, hydroxy, halogen, —

C(O)OH, —

C(O)O-lower alkyl or —

C(O)O-lower alkyl-phenyl,

-5- or 6-membered heterocycloalkyl, unsubstituted or substituted, with one to four substituents from lower alkyl, hydroxy, halogen, —

SO₂-loweralkyl, —

C(O)OH, —

C(O)O-lower alkyl or —

C(O)O-lower alkyl-phenyl,

-5- or 6-membered aryl, unsubstituted or substituted with one to four substituents from

lower alkyl, hydroxy, halogen, —

C(O)OH, —

C(O)O-lower alkyl or —

C(O)O-lower alkyl-phenyl,

-5- or 6-membered heteroaryl, unsubstituted or substituted with one to four substituents from lower alkyl, hydroxy, halogen, —

C(O)OH, C(O)O-lower alkyl or —

C(O)O-lower alkyl-phenyl,

—

(CH₂)_nC(O)OH,

—

CH₂C(lower alkyl)₂C(O)OH,

—

CH₂(cycloalkyl)C(O)OH,

-(cycloalkyl)C(O)OH,

—

CH₂C(CH₃)₃,

—

(CH₂)_n-cycloalkyl,

-cycloalkenyl,

-bicycloalkenyl-C(O)OH,

—

(CH₂)_n—

O-alkyl,

—

O—

C(═

C)-lower alkyl,

—

O—

(CH₂)_n-phenyl,

—

NSO₂-loweralkyl,

—

NSO₂-cycloalkyl,

—

NSO₂-aryl,

—

N-lower alkyl,

—

N-cycloalkyl, said cycloalkyl being unsubstituted or substituted with —

C(O)OH,

—

N-heterocycloalkyl,

—

N-aryl,

—

N—

(CH₂)_n-aryl,

—

N-heteroaryl, said heteroaryl being unsubstituted or substituted with alkyl,

—

N—

CH(lower alkyl)C(O)OH,

—

N-(cycloalkyl)C(O)OH,

—

N—

CH(lower alkyl)C(O)O-lower alkyl,

-phenyl-C(O)OH,

X is 5- or 6-membered aryl, unsubstituted or substituted with lower alkyl, halogen or cyano;

Y is phenyl, heteroaryl, cycloloweralkyl, or 5- or 6-membered heterocycloalkyl, —

N(CH₂)_n)N—

, said phenyl, cycloloweralkyl or heterocycloalkyl being unsubstituted or substituted with lower alkyl, halogen or cyano;

n is 1, 2 or 3.

5. The compound according to claim 1, wherein:

R₁ is phenyl or 5- or 6-membered heteroaryl, said phenyl and heteroaryl being unsubstituted or substituted with halogen, lower alkyl, alkoxy or O—

CF₃;

R₂ is halogen, lower alkyl, haloloweralkyl or alkoxy;

R₃ is nitrogen, oxygen or absent, said nitrogen being unsubstituted or substituted with lower alkyl;

R₄ is carbon, nitrogen, oxygen or absent, said carbon or nitrogen being unsubstituted or substituted with lower alkyl;

wherein both R₃ and R₄ are not absent;

R₅ is -loweralkyl,

-alkoxy,

-hydroxy,

-amine,

-lower alkyl amine,

-haloloweralkyl,

-lower alkoxy,

-lower alkenyloxy,

-cycloloweralkyl, unsubstituted or substituted with one to four substituents from lower

alkyl, hydroxy, halogen, —

C(O)OH, —

C(O)O-lower alkyl or —

C(O)O-lower alkyl-phenyl,

-5- or 6-membered heterocycloalkyl, unsubstituted or substituted, with one to four substituents from lower alkyl, hydroxy, halogen, —

SO₂-loweralkyl, —

C(O)OH, —

C(O)O-lower alkyl or —

C(O)O-lower alkyl-phenyl,

-5- or 6-membered aryl, unsubstituted or substituted with one to four substituents from

lower alkyl, hydroxy, halogen, —

C(O)OH, —

C(O)O-lower alkyl or —

C(O)O-lower alkyl-phenyl,

-5- or 6-membered heteroaryl, unsubstituted or substituted with one to four substituents from lower alkyl, hydroxy, halogen, —

C(O)OH, C(O)O-lower alkyl or —

C(O)O-lower alkyl-phenyl,

—

(CH₂)_nC(O)OH,

—

CH₂C(lower alkyl)₂C(O)OH,

—

CH₂(cycloalkyl)C(O)OH,

-(cycloalkyl)C(O)OH,

—

CH₂C(CH₃)₃,

—

(CH₂)_n-cycloalkyl,

-cycloalkenyl,

-bicycloalkenyl-C(O)OH,

—

(CH₂)_n—

O-alkyl,

—

O—

C(═

C)-lower alkyl,

—

O—

(CH₂)_n-phenyl,

—

NSO₂-loweralkyl,

—

NSO₂-cycloalkyl,

—

NSO₂-aryl,

—

N-lower alkyl,

—

N-cycloalkyl, said cycloalkyl being unsubstituted or substituted with —

C(O)OH,

—

N-heterocycloalkyl,

—

N-aryl,

—

N—

(CH₂)_n-aryl,

—

N-heteroaryl, said heteroaryl being unsubstituted or substituted with alkyl,

—

N—

CH(lower alkyl)C(O)OH,

—

N-(cycloalkyl)C(O)OH,

—

N—

CH(lower alkyl)C(O)O-lower alkyl,

-phenyl-C(O)OH,

X is 5- or 6-membered heteroaryl, unsubstituted or substituted with lower alkyl, halogen or cyano;

Y is phenyl, heteroaryl, cycloloweralkyl, or 5- or 6-membered heterocycloalkyl, —

N(CH₂)_n)N—

, said phenyl, cycloloweralkyl or heterocycloalkyl being unsubstituted or substituted with lower alkyl, halogen or cyano;

n is 1, 2 or 3.

6. The compound according to claim 1, wherein:

R₁ is phenyl or 5- or 6-membered heteroaryl, said phenyl and heteroaryl being unsubstituted or substituted with halogen, lower alkyl, alkoxy or O—

CF₃;

R₂ is halogen, lower alkyl, haloloweralkyl or alkoxy;

R₃ is nitrogen, oxygen or absent, said nitrogen being unsubstituted or substituted with lower alkyl;

R₄ is carbon, nitrogen, oxygen or absent, said carbon or nitrogen being unsubstituted or substituted with lower alkyl;

wherein both R₃ and R₄ are not absent;

R₅ is -loweralkyl,

-alkoxy,

-hydroxy,

-amine,

-lower alkyl amine,

-haloloweralkyl,

-lower alkoxy,

-lower alkenyloxy,

-cycloloweralkyl, unsubstituted or substituted with one to four substituents from lower

alkyl, hydroxy, halogen, —

C(O)OH, —

C(O)O-lower alkyl or —

C(O)O-lower alkyl-phenyl,

-5- or 6-membered heterocycloalkyl, unsubstituted or substituted, with one to four substituents from lower alkyl, hydroxy, halogen, —

SO₂-loweralkyl, —

C(O)OH, —

C(O)O-lower alkyl or —

C(O)O-lower alkyl-phenyl,

-5- or 6-membered aryl, unsubstituted or substituted with one to four substituents from

lower alkyl, hydroxy, halogen, —

C(O)OH, —

C(O)O-lower alkyl or —

C(O)O-lower alkyl-phenyl,

-5- or 6-membered heteroaryl, unsubstituted or substituted with one to four substituents from lower alkyl, hydroxy, halogen, —

C(O)OH, C(O)O-lower alkyl or —

C(O)O-lower alkyl-phenyl,

—

(CH₂)_nC(O)OH,

—

CH₂C(lower alkyl)₂C(O)OH,

—

CH₂(cycloalkyl)C(O)OH,

-(cycloalkyl)C(O)OH,

—

CH₂C(CH₃)₃,

—

(CH₂)_n-cycloalkyl,

-cycloalkenyl,

-bicycloalkenyl-C(O)OH,

—

(CH₂)_n—

O-alkyl,

—

O—

C(═

C)-lower alkyl,

—

O—

(CH₂)_n-phenyl,

—

NSO₂-loweralkyl,

—

NSO₂-cycloalkyl,

—

NSO₂-aryl,

—

N-lower alkyl,

—

N-cycloalkyl, said cycloalkyl being unsubstituted or substituted with —

C(O)OH,

—

N-heterocycloalkyl,

—

N-aryl,

—

N—

(CH₂)_n-aryl,

—

N-heteroaryl, said heteroaryl being unsubstituted or substituted with alkyl,

—

N—

CH(lower alkyl)C(O)OH,

—

N-(cycloalkyl)C(O)OH,

—

N—

CH(lower alkyl)C(O)O-lower alkyl,

-phenyl-C(O)OH,

X is 5- or 6-membered aryl or 5- or 6-membered heteroaryl, said aryl or heteroaryl being unsubstituted or substituted with lower alkyl, halogen or cyano;

Y is phenyl, unsubstituted or substituted with lower alkyl, halogen or cyano; and

n is 1, 2 or 3.

7. The compound according to claim 1, wherein:

R₁ is phenyl or 5- or 6-membered heteroaryl, said phenyl and heteroaryl being unsubstituted or substituted with halogen, lower alkyl, alkoxy or O—

CF₃;

is halogen, lower alkyl, haloloweralkyl or alkoxy;

R₃ is nitrogen, oxygen or absent, said nitrogen being unsubstituted or substituted with lower alkyl;

R₄ is carbon, nitrogen, oxygen or absent, said carbon or nitrogen being unsubstituted or substituted with lower alkyl;

wherein both R₃ and R₄ are not absent;

R₅ is -loweralkyl,

-alkoxy,

-hydroxy,

-amine,

-lower alkyl amine,

-haloloweralkyl,

-lower alkoxy,

-lower alkenyloxy,

-cycloloweralkyl, unsubstituted or substituted with one to four substituents from lower

alkyl, hydroxy, halogen, —

C(O)OH, —

C(O)O-lower alkyl or —

C(O)O-lower alkyl-phenyl,

-5- or 6-membered heterocycloalkyl, unsubstituted or substituted, with one to four substituents from lower alkyl, hydroxy, halogen, —

SO₂-loweralkyl, —

C(O)OH, —

C(O)O-lower alkyl or —

C(O)O-lower alkyl-phenyl,

-5- or 6-membered aryl, unsubstituted or substituted with one to four substituents from

lower alkyl, hydroxy, halogen, —

C(O)OH, —

C(O)O-lower alkyl or —

C(O)O-lower alkyl-phenyl,

-5- or 6-membered heteroaryl, unsubstituted or substituted with one to four substituents from lower alkyl, hydroxy, halogen, —

C(O)OH, C(O)O-lower alkyl or —

C(O)O-lower alkyl-phenyl,

—

(CH₂)_nC(O)OH,

—

CH₂C(lower alkyl)₂C(O)OH,

—

CH₂(cycloalkyl)C(O)OH,

-(cycloalkyl)C(O)OH,

—

CH₂C(CH₃)₃,

—

(CH₂)_n-cycloalkyl,

-cycloalkenyl,

-bicycloalkenyl-C(O)OH,

—

(CH₂)_n—

O-alkyl,

—

O—

C(═

C)-lower alkyl,

—

O—

(CH₂)_n-phenyl,

—

NSO₂-loweralkyl,

—

NSO₂-cycloalkyl,

—

NSO₂-aryl,

—

N-lower alkyl,

—

N-cycloalkyl, said cycloalkyl being unsubstituted or substituted with —

C(O)OH,

—

N-heterocycloalkyl,

—

N-aryl,

—

N—

(CH₂)_n-aryl,

—

N-heteroaryl, said heteroaryl being unsubstituted or substituted with alkyl,

—

N—

CH(lower alkyl)C(O)OH,

—

N-(cycloalkyl)C(O)OH,

—

N—

CH(lower alkyl)C(O)O-lower alkyl,

-phenyl-C(O)OH,

X is 5- or 6-membered aryl or 5- or 6-membered heteroaryl, said aryl or heteroaryl being unsubstituted or substituted with lower alkyl, halogen or cyano;

Y is cycloloweralkyl or 5- or 6-membered heterocycloalkyl, said cycloloweralkyl or heterocycloalkyl being unsubstituted or substituted with lower alkyl, halogen or cyano; and

n is 1, 2 or 3.

8. The compound according to claim 1, wherein:

R₁ is phenyl, unsubstituted or substituted with halogen, lower alkyl, alkoxy or O—

CF₃; and

X is 5- or 6-membered aryl, unsubstituted or substituted with lower alkyl, halogen or cyano.

9. The compound according to claim 1, wherein:

R₁ is phenyl, unsubstituted or substituted with halogen, lower alkyl, alkoxy or O—

CF₃; and

X is 5- or 6-membered heteroaryl, unsubstituted or substituted with lower alkyl, halogen or cyano.

10. The compound according to claim 1, wherein:

R₁ is 5- or 6-membered heteroaryl, unsubstituted or substituted with halogen, lower alkyl, alkoxy or O—

CF₃; and

X is 5- or 6-membered aryl, unsubstituted or substituted with lower alkyl, halogen or cyano.

11. The compound according to claim 1, wherein:

R₁ is 5- or 6-membered heteroaryl, unsubstituted or substituted with halogen, lower alkyl, —

O-lower alkyl or O—

CF₃; and

X is 5- or 6-membered heteroaryl, unsubstituted or substituted with lower alkyl, halogen or cyano.

12. The compound according to claim 1, wherein:

R₁ is phenyl, unsubstituted or substituted with halogen, lower alkyl, alkoxy or O—

CF₃; and

Y is phenyl, unsubstituted or substituted with lower alkyl, halogen or cyano.

13. The compound according to claim 1, wherein:

R₁ is 5- or 6-membered heteroaryl, unsubstituted or substituted with halogen, lower alkyl, alkoxy or O—

CF₃; and

Y is phenyl, unsubstituted or substituted with lower alkyl, halogen or cyano.

14. The compound according to claim 1, wherein:

R₁ is phenyl, unsubstituted or substituted with halogen, lower alkyl, alkoxy or O—

CF₃; and

Y is cycloloweralkyl or 5- or 6-membered heterocycloalkyl, said cycloloweralkyl or heterocycloalkyl being unsubstituted or substituted with lower alkyl, halogen or cyano.

15. The compound according to claim 1, wherein:

R₁ is 5- or 6-membered heteroaryl, unsubstituted or substituted with halogen, lower alkyl, alkoxy or O—

CF₃; and

Y is cycloloweralkyl or 5- or 6-membered heterocycloalkyl, said cycloloweralkyl or heterocycloalkyl being unsubstituted or substituted with lower alkyl, halogen or cyano.

16. The compound according to claim 1, wherein:

X is 5- or 6-membered aryl, unsubstituted or substituted with lower alkyl, halogen or cyano; and

Y is phenyl, heteroaryl, cycloloweralkyl, or 5- or 6-membered heterocycloalkyl, —

N(CH₂)_n)N—

, said phenyl, cycloloweralkyl or heterocycloalkyl being unsubstituted or substituted with lower alkyl, halogen or cyano.

17. The compound according to claim 1, wherein:

X is 5- or 6-membered heteroaryl, unsubstituted or substituted with lower alkyl, halogen or cyano; and

Y is phenyl, heteroaryl, cycloloweralkyl, or 5- or 6-membered heterocycloalkyl, —

N(CH₂)_n)N—

, said phenyl, cycloloweralkyl or heterocycloalkyl being unsubstituted or substituted with lower alkyl, halogen or cyano.

18. The compound according to claim 1, wherein:

X is 5- or 6-membered aryl or 5- or 6-membered heteroaryl, said aryl or heteroaryl being unsubstituted or substituted with lower alkyl, halogen or cyano; and

Y is phenyl, unsubstituted or substituted with lower alkyl, halogen or cyano.

19. The compound according to claim 1, wherein:

X is 5- or 6-membered aryl or 5- or 6-membered heteroaryl, said aryl or heteroaryl being unsubstituted or substituted with lower alkyl, halogen or cyano; and

Y is cycloloweralkyl or 5- or 6-membered heterocycloalkyl, said cycloloweralkyl or heterocycloalkyl being unsubstituted or substituted with lower alkyl, halogen or cyano.

20. The compound according to claim 1, wherein R₁ is phenyl, unsubstituted or substituted with halogen.

21. The compound according to claim 1, wherein R₁ is pyridine, unsubstituted or substituted with halogen.

22. The compound according to claim 1, wherein R₂ is halogen, trifluoromethyl, trifluoroethyl, methyl, ethyl, propyl, methoxymethyl or methoxyethyl.

23. The compound according to claim 1, wherein R₅ is lower alkyl, alkoxy, hydroxy, lower alkyl amine;

cycloloweralkyl, unsubstituted or substituted with one to four substituents from loweralkyl, hydroxy, halogen, —

C(O)OH, —

C(O)O-lower alkyl or —

C(O)O-lower alkyl-phenyl;

5- or 6-membered heterocycloalkyl, unsubstituted or substituted, with one to four substituents from lower alkyl, hydroxy, halogen, —

SO₂-loweralkyl, —

C(O)OH, —

C(O)O-lower alkyl or —

C(O)O-lower alkyl-phenyl;

(CH₂)_nC(O)OH;

CH₂C(lower alkyl)₂C(O)OH;

CH₂(cycloalkyl)C(O)OH;

(cycloalkyl)C(O)OH;

NSO₂-loweralkyl;

N-lower alkyl;

N-cycloalkyl, said cycloalkyl being unsubstituted or substituted with —

C(O)OH;

N—

CH(lower alkyl)C(O)OH;

or —

N-(cycloalkyl)C(O)OH.

24. The compound according to claim 1, wherein X is phenyl, pyridine or pyrimidine.

25. The compound according to claim 1, wherein Y is phenyl, pyridine, piperazine, piperidine, pyrrolidine or cyclopentane.

26. The compound according to claim 1, wherein R₃ is nitrogen, unsubstituted or substituted with lower alkyl.

27. The compound according to claim 1, wherein R₄ is nitrogen, unsubstituted or substituted with lower alkyl.

28. The compound according to claim 1, wherein n is 1.

29. The compound according to claim 1, selected from the group consisting of:

(1R,2R)-2-{4′

-[(2-Phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-biphenyl-4-ylcarbamoyl}-cyclopentanecarboxylic acid, (1S,2S)-2-{4′

-[(2-Phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-biphenyl-4-ylcarbamoyl}-cyclopentanecarboxylic acid, (S)-3-(5-{[2-(2-Trifluoromethoxy-phenyl)-5-trifluoromethyl-oxazole-4-carbonyl]-amino}-pyrimidin-2-yloxy)-pyrrolidine-1-carboxylic acid ethyl ester, (S)-3-{5-[(2-Phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-pyridin-2-yloxy}-pyrrolidine-1-carboxylic acid ethyl ester, (S)-3-(4-{[2-(2-Trifluoromethoxy-phenyl)-5-trifluoromethyl-oxazole-4-carbonyl]-amino}-phenylamino)-pyrrolidine-1-carboxylic acid ethyl ester, 2-Phenyl-5-trifluoromethyl-oxazole-4-carboxylic acid [6-((S)-1-isobutyryl-pyrrolidin-3-ylamino)-pyridin-3-yl]-amide, 2,2-Dimethyl-3-{5′

-[(2-phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-3,4,5,6-tetrahydro-2H-[1,2′

]bipyridinyl-4-yl}-propionic acid, (S)-3-(5-{[2-(2-Trifluoromethoxy-phenyl)-5-trifluoromethyl-oxazole-4-carbonyl]-amino}-pyridin-2-ylamino)-pyrrolidine-1-carboxylic acid ethyl ester, (S)-3-{4-[(2-Phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-phenylamino}-pyrrolidine-1-carboxylic acid ethyl ester, and (S)-3-(5-{[2-(2-Trifluoromethoxy-phenyl)-5-trifluoromethyl-oxazole-4-carbonyl]-amino}-pyrimidin-2-ylamino)-pyrrolidine-1-carboxylic acid ethyl ester.

30. A pharmaceutical composition, comprising a therapeutically effective amount of a compound according to claim 1 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.

31. A method of treating obesity, type II diabetes, dyslipidemia or metabolic syndrome, comprising the step of administering a therapeutically effective amount of a compound according to claim 1 to a patient in need thereof.