BIPHENYL-2-CARBONIC ACID-TETRAHYDRO-ISOCHINOLIN-6-YL AMIDE DERIVATIVES, THEIR PREPARATION AND THE USE THEREOF AS INHIBITORS OF THE MICROSOMAL TRIGLYCERIDE TRANSFER PROTEIN AND / OR THE APOLIPOPROTEIN B (APO BION.)

摘要

PCT No. PCT/IB95/00448 Sec. 371 Date Nov. 28, 1997 Sec. 102(e) Date Nov. 28, 1997 PCT Filed Jun. 7, 1995 PCT Pub. No. WO96/40640 PCT Pub. Date Dec. 19, 1996Compounds of formula (I), wherin X is CH2, CO, CS or SO2; Y is selected from: a direct link, aliphatic hydrocarbylene radicals having up to 20 carbon atoms, which radical may be mono-substituted by hydroxy, (C1-C10)alkoxy, (C1-C10)acyl, (C1-C10)acyloxy, or (C6-C10)aryl, NH, and O, provided that if X is CH2,Y is a direct link; Z is selected from the following groups: (1) H, halo, cyano, (2) hydroxy, (C1-C10)alkoxy, (C1-C10)a1kylthio, (C1-C10)acyl, thiophenylcaronyl (C1-C10)alkoxycarbonyl, (3) (C1-C10)aklkyammo, di(C1-C10)alylamino, (C6-C10)aryl(C1-C10)alkylamino, provided that Y is not O or NH, (4) unsubstituted vinyl, (C6-C10)aryl, (C3-C8)cycloalkyl and fused benz derivatives thereof, (C7-C10)polycycloalkyl, (C4-C8)cycloalkenyl, (C7-C10)polycycloalkenyl, (5) (C6-C10)aryloxy, (C6-C10)aryltio, (C6-C10)aryl(C1-C10)alkoxy, (C6-C10)aryl(C1-C10)alkylthio, (C3-C8)cycloalkyloxy, (C4-C8)cycloalkenyloxy, (6) heterocyclyl sclected from the group consisting of monocyclic radicals and fused polycycuic radicals, wherein said radicals contain a total of from 5 to 14 ring atoms, wherein said radicals contain a total of from 1 to 4 ring heteroatoms independently selocted from oxygen, nitrogen, and sulfur, and wherein the individual rings of said radicals may be independendy satated, partally unsaturated, or aromatic, provided that if X is CH2, Z is H or is selected from groups (4) and (6), wherein, when Z contains one or more rings, said rings may each independently bear 0 to 4 substituents independently selected from halo, hydroxy, cyano, nitro, oxo, thioxo, aminosulfonyl, phenyl phenoxy, phenylthio, halophenylthio, benzyl, benzyloxy, (C1-C10)alkyl, (C1-C10)alkoxy, (C1-C10)alkoxycarbonyl, (C1-C10)althyltio, (C1-C10)altylamino, (C1-C10)alkylaminocarbonyl, di(C1-C10)alkylamino, di(C1-C10)alkylaminocarbonyl, di(C1-C10)alkyo(C1-C10)alkoxy, (C1-C3)perfluoroalkyl, (C1-C3)perfluoroalkoxy, (C1-C10)acyl, (C1-C10)acyloxy, (C1-C10)acyloxy(C1-C10)alkyl, and pyrrolidinyl; and pharmaceutically acceptable salts thereof.