公开(公告)号：WO1996040640A1

公开(公告)日：1996-12-19

申请号：PCT/IB1995000448

申请日：1995-06-07

Applicant: PFIZER INC. ,  CHANG, George ,  DORFF, Peter, H. ,  QUALLICH, George, J.

Inventor： PFIZER INC.

IPC: C07D217/04

CPC classification number: C07D401/06 ,  C07D217/04 ,  C07D217/06 ,  C07D401/10 ,  C07D405/06 ,  C07D409/06 ,  C07D413/06 ,  C07D417/06

Abstract: Compounds of formula (I), wherein 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)alkylthio, (C1-C10)acyl, thiophenylcarbonyl, (C1-C10)alkoxycarbonyl, (3) (C1-C10)alkylamino, di(C1-C10)alkylamino, (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)arylthio, (C6-C10)aryl(C1-C10)alkoxy, (C6-C10)aryl(C1-C10)alkylthio, (C3-C8)cycloalkyloxy, (C4-C8)cycloalkenyloxy, (6) heterocyclyl selected from the group consisting of monocyclic radicals and fused polycyclic 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 selected from oxygen, nitrogen, and sulfur, and wherein the individual rings of said radicals may be independently saturated, partially 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)alkylthio, (C1-C10)alkylamino, (C1-C10)alkylaminocarbonyl, di(C1-C10)alkylamino, di(C1-C10)alkylaminocarbonyl, di(C1-C10)alkylamino(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. This invention relates to compounds which are inhibitors of microsomal triglyceride transfer protein and/or apolipoprotein B (Apo B) secretion, and which are accordingly useful for the prevention and treatment of atherosclerosis and its clinical sequelae, for lowering serum lipids, and related diseases. The invention further relates to compositions comprising the compounds and to methods of treating atherosclerosis, obesity, and related diseases and/or conditions with the compounds.

Abstract translation: 式（I）化合物，其中X为CH 2，CO，CS或SO 2; Y选自：直接键合，具有至多20个碳原子的脂族亚烃基，该基团可以被羟基，（C1-C10）烷氧基，（C1-C10）酰基，（C1-C10）酰氧基， 或（C 6 -C 10）芳基，NH和O，条件是如果X是CH 2，则Y是直链; Z选自以下基团：（1）H，卤素，氰基，（2）羟基，（C1-C10）烷氧基，（C1-C10）烷硫基，（C1-C10）酰基，苯硫基羰基，（C1-C10） 烷氧基羰基，（3）（C1-C10）烷基氨基，二（C1-C10）烷基氨基，（C6-C10）芳基（C1-C10）烷基氨基，条件是Y不为O或NH，（4）未取代的乙烯基，（C6 -C（C 10）芳基，（C 3 -C 8）环烷基和其稠合苯并衍生物，（C 7 -C 10）多环烷基，（C 4 -C 8）环烯基，（C 7 -C 10）多环烯基，（5） （C 1 -C 10）芳基（C 1 -C 10）烷氧基，（C 6 -C 10）芳基（C 1 -C 10）烷硫基，（C 3 -C 8）环烷氧基，（C 8 -C 8）环链烯氧基，（6） 由单环基团和稠合多环基团组成，其中所述基团含有总共5至14个环原子，其中所述基团含有总共1至4个独立地选自氧，氮和硫的环杂原子，以及 其中所述基团的各个环可以独立地是饱和的，部分不饱和的或芳族的 条件是如果X是CH 2，Z是H或选自基团（4）和（6），其中当Z含有一个或多个环时，所述环各自独立地具有0至4个独立地选自卤素， 羟基，氰基，硝基，氧代，硫代，氨基磺酰基，苯基，苯氧基，苯硫基，卤代苯硫基，苄基，苄氧基，（C1-C10）烷基，（C1-C10）烷氧基，（C1-C10）烷氧羰基，（C1-C10） （C1-C10）烷基氨基，（C1-C10）烷基氨基羰基，二（C1-C10）烷基氨基，二（C1-C10）烷基氨基羰基，二（C1-C10）烷基氨基（C1-C10）烷氧基，（C1-C3） 全氟烷基，（C1-C3）全氟烷氧基，（C1-C10）酰基，（C1-C10）酰氧基，（C1-C10）酰氧基（C1-C10）烷基和吡咯烷基; 及其药学上可接受的盐。 本发明涉及作为微粒体甘油三酯转运蛋白和/或载脂蛋白B（Apo B）分泌抑制剂的化合物，其相应地可用于预防和治疗动脉粥样硬化及其临床后遗症，降低血清脂质和相关疾病。 本发明进一步涉及包含该化合物的组合物以及用该化合物治疗动脉粥样硬化，肥胖症和相关疾病和/或病症的方法。