Bicyclic compounds as inhibitors of diacylglycerol acyltransferase
View Patent ↗The present invention relates to novel heterocyclic compounds as diacylglycerol acyltransferase (“DGAT”) inhibitors, pharmaceutical compositions comprising the heterocyclic compounds and the use of the compounds for treating or preventing a cardiovascular disease, a metabolic disorder, obesity or an obesity-related disorder, diabetes, dyslipidemia, a diabetic complication, impaired glucose tolerance or impaired fasting glucose. An illustrative compound of the invention is shown below: formula (I).
1. A compound, or pharmaceutically acceptable salt of said compound, the compound being represented by the Formula IB
or a stereoisomer or tautomer of said compound, wherein
the bond denoted by represents a single bond;
E is O;
F is C(R 4 R 4 );
G is C(R 4 R 4 );
H is N(R 4′ );
R 4 is present depending on the allowed vacancy and is selected from H, alkyl, or hydroxyalkyl;
R 4′ is present depending on the allowed vacancy and is R 1 ;
R 1 is selected from the group consisting of (alkylamino)carbonyl, (cycloalkylamino)carbonyl, (heterocycloalkylamino)carbonyl, and (arylamino)carbonyl, wherein each of these R 1 groups is unsubstituted or optionally independently substituted with 1-4 substituents independently selected from halogen, amino, alkylamino, hydroxy, alkoxy, alkyl, cycloalkyl, carboxy, carboxyester, methylenedioxy, CN, cyanoalkyl-, nitro and CF 3 ;
A is CR 5 ;
B is CR 5 ;
C is CR 5 ;
D is CR 5 ;
R 5 is selected from H, alkyl, or halogen, wherein each of these R 5 groups is unsubstituted or optionally independently substituted with 1-4 substituents independently selected from halogen, amino, alkylamino, hydroxy, alkoxy, alkyl, cycloalkyl, CN and CF 3 ;
R 2 is heteroaryl, wherein said heteroaryl is a six-membered aromatic ring system containing 1 to 2 N atoms, and wherein said heteroaryl is unsubstituted or optionally independently substituted with 1-4 substituents independently selected from halogen, amino, alkylamino, hydroxy, alkoxy, alkyl, cycloalkyl, CN and CF 3 ;
Z is O; and
R 3 is selected from the group consisting of alkyl or cycloalkyl.
2. A pharmaceutical composition comprising at least one compound of claim 1 and at least one pharmaceutically acceptable carrier.
3. A method of treating obesity, diabetes or metabolic syndrome in a patient in need thereof comprising administering therapeutically effective amounts of at least one compound of claim 1 to said patient.
4. A compound selected from the compounds of the formulae:
or a pharmaceutically acceptable salt thereof.