N-aryl piperidine substituted biphenylcarboxamides as inhibitors of apolipoprotein b

摘要

N-aryl piperidine substituted biphenylcarboxamides compounds of formula (I);
methods for preparing such compounds, pharmaceutical compositions comprising said compounds as well as the use of said compounds as a medicine for the treatment of hyperlipidemia, obesity and type II diabetes.

主权项

1. A compound of formula (I) the N-oxides, the pharmaceutically acceptable acid addition salts and the stereochemically isomeric forms thereof, wherein R1 is hydrogen, C1-4alkyl, halo, or polyhaloC1-4alkyl; R2 is hydrogen, C1-4alkyl, halo, or polyhaloC1-4alkyl; R3 is hydrogen or C1-4alkyl; R4 is hydrogen, C1-4alkyl, or halo; n is an integer 0, or 1; X1 is carbon and X2 is carbon; or X1 is nitrogen and X2 is carbon; or X1 is carbon and X2 is nitrogen; X3 is carbon or nitrogen; Y represents O, or NR6 wherein R6 is hydrogen or C1-4alkyl; R5 represents a radical of formula whereinm is an integer 0, 1, or 2;Z is O or NH;R7 is hydrogen,
C1-6alkyl;C1-6alkyl substituted with hydroxy, amino, mono- or di(C1-4alkyl)amino, C1-4alkyloxycarbonyl, aminocarbonyl, aryl or heteroaryl;C1-4alkyl-O—C1-4alkyl;C1-4alkyl-S—C1-4alkyl; oraryl;R8 is hydrogen or C1-6alkyl;R9 is C1-4alkyl; or when Y represents NR6 the radicals R5 and R6 may be taken together with the nitrogen to which they are attached to form pyrrolidinyl substituted with C1-4alkyloxycarbonyl and optionally further substituted with hydroxy; or piperidinyl substituted with C1-4alkyloxycarbonyl; aryl is phenyl; phenyl substituted with one, two or three substituents each independently selected from C1-4alkyl, C1-4alkyloxy, halo, hydroxy, nitro, cyano, C1-4alkyloxycarbonyl, trifluoromethyl, or trifluoromethoxy; or benzo[1,3]dioxolyl; and heteroaryl is imidazolyl, thiazolyl, indolyl, or pyridinyl.