Compounds as diacylglycerol acyltransferase inhibitors

摘要

This invention relates to novel compounds which are inhibitors of acyl coenzymeA: diacylglycerol acyltransferase 1 (DGAT-1), to pharmaceutical compositions containing them, to processes for their preparation, and to their use in therapy for the prevention or treatment of diseases related to DGAT-1 dysfunction or where modulation of DGAT-1 activity may have therapeutic benefit including but not limited to obesity, obesity related disorders, hypertriglyceridemia, hyperlipoproteinemia, chylomicronemia, dyslipidemia, non-alcoholic steatohepatitis, diabetes, insulin resistance, metabolic syndrome, hepatitis C virus infection and acne or other skin disorders.

主权项

1. A compound of Formula (I):wherein
R1 is a bicyclic ring system which contains 9 to 11 ring members including 1 to 4 heteroatoms independently selected from the group consisting of N, O, and S, in which said bicyclic ring system may be substituted by 1 to 3 groups independently selected from the group consisting of C1-C6alkyl, substituted C1-C6alkyl, C3-C7cycloalkyl, halo, hydroxyl, oxo, —C(O)NRcRd, —COOH, —C(O)Ra, —SO2Ra, arylalkyl, —(C1-C3alkyl)aryloxy, aryl, heteroaryl and C1-C4alkoxy, in which each Ra is independently C1-C6alkyl, substituted C1-C6alkyl or unsubstituted C3-C7cycloalkyl; each R2 and R3 is independently hydrogen, C1-C6alkyl, substituted C1-C6alkyl, halo, hydroxyl, —C(O)NRcRd, —COOH or C1-C4alkoxy; and m is 0-2; wherein any said substituted C1-C6alkyl is substituted by 1 to 3 groups independently selected from the group consisting of unsubstituted C3-C7cycloalkyl, methyl, ethyl, propyl, isopropyl, butyl, t-butyl, difluoromethyl, trifluoromethyl, halo, —NR′R″, cyano, hydroxyl, C1-C4alkoxy, —COOH, —COO(methyl), —COO(ethyl), and —C(O)NRcRd, wherein R′ and R″ are each independently selected from the group consisting of hydrogen, unsubstituted C1-C6alkyl, —C(O)Rb, and unsubstituted C3-C7cycloalkyl, wherein Rb is unsubstituted C1-C6alkyl, C3-C7cycloalkyl, or heterocyclyl; and wherein each Rc and Rd are independently hydrogen or C1-C6alkyl; or a pharmaceutically acceptable salt thereof.