Diacylglycerol Acyltransferase Inhibitors
First Claim
Patent Images
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 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,-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,
5 Assignments
0 Petitions
Accused Products
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.
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Citations
31 Claims
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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; andn is 1, 2 or 3, or pharmaceutically acceptable salts thereof,
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2. The compound according to claim 1, wherein:
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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.
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3. The compound according to claim 1, wherein:
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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.
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4. The compound according to claim 1, wherein:
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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.
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5. The compound according to claim 1, wherein:
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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.
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6. The compound according to claim 1, wherein:
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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.
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7. The compound according to claim 1, wherein:
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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.
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8. The compound according to claim 1, wherein:
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R1 is phenyl, unsubstituted or substituted with halogen, lower alkyl, alkoxy or O—
CF3; andX is 5- or 6-membered aryl, unsubstituted or substituted with lower alkyl, halogen or cyano.
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9. The compound according to claim 1, wherein:
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R1 is phenyl, unsubstituted or substituted with halogen, lower alkyl, alkoxy or O—
CF3; andX is 5- or 6-membered heteroaryl, unsubstituted or substituted with lower alkyl, halogen or cyano.
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10. The compound according to claim 1, wherein:
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R1 is 5- or 6-membered heteroaryl, unsubstituted or substituted with halogen, lower alkyl, alkoxy or O—
CF3; andX is 5- or 6-membered aryl, unsubstituted or substituted with lower alkyl, halogen or cyano.
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11. The compound according to claim 1, wherein:
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R1 is 5- or 6-membered heteroaryl, unsubstituted or substituted with halogen, lower alkyl, —
O-lower alkyl or O—
CF3; andX is 5- or 6-membered heteroaryl, unsubstituted or substituted with lower alkyl, halogen or cyano.
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12. The compound according to claim 1, wherein:
-
R1 is phenyl, unsubstituted or substituted with halogen, lower alkyl, alkoxy or O—
CF3; andY is phenyl, unsubstituted or substituted with lower alkyl, halogen or cyano.
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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; andY is phenyl, unsubstituted or substituted with lower alkyl, halogen or cyano.
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14. The compound according to claim 1, wherein:
-
R1 is phenyl, unsubstituted or substituted with halogen, lower alkyl, alkoxy or O—
CF3; andY is cycloloweralkyl or 5- or 6-membered heterocycloalkyl, said cycloloweralkyl or heterocycloalkyl being unsubstituted or substituted with lower alkyl, halogen or cyano.
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15. The compound according to claim 1, wherein:
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R1 is 5- or 6-membered heteroaryl, unsubstituted or substituted with halogen, lower alkyl, alkoxy or O—
CF3; andY is cycloloweralkyl or 5- or 6-membered heterocycloalkyl, said cycloloweralkyl or heterocycloalkyl being unsubstituted or substituted with lower alkyl, halogen or cyano.
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16. The compound according to claim 1, wherein:
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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.
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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.
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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.
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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.
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20. The compound according to claim 1, wherein R1 is phenyl, unsubstituted or substituted with halogen.
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21. The compound according to claim 1, wherein R1 is pyridine, unsubstituted or substituted with halogen.
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22. The compound according to claim 1, wherein R2 is halogen, trifluoromethyl, trifluoroethyl, methyl, ethyl, propyl, methoxymethyl or methoxyethyl.
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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.
- cycloloweralkyl, unsubstituted or substituted with one to four substituents from loweralkyl, hydroxy, halogen, —
-
24. The compound according to claim 1, wherein X is phenyl, pyridine or pyrimidine.
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25. The compound according to claim 1, wherein Y is phenyl, pyridine, piperazine, piperidine, pyrrolidine or cyclopentane.
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26. The compound according to claim 1, wherein R3 is nitrogen, unsubstituted or substituted with lower alkyl.
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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.
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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.
- (1R,2R)-2-{4′
-
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.
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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.
Specification