Bicyclic compounds as inhibitors of diacylglycerol acyltransferase
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.