发明名称 SPIROCYCLIC CETP INHIBITORS
摘要 Compounds having the structure of Formula (I), including pharmaceutically acceptable salts of the compounds, are CETP inhibitors and may be useful for raising HDL-cholesterol and reducing LDL-cholesterol in human patients and for treating or preventing atherosclerosis. The chemical compounds that are disclosed cholesterol ester transfer protein (CETP) and are expected to have utility in raising HDL-C, lowering LDL-C, and in the treatment and prevention of atherosclerosis.
申请公布号 US2015342931(A1) 申请公布日期 2015.12.03
申请号 US201314653445 申请日期 2013.12.17
申请人 MERCK SHARP & DOHME CORP. 发明人 Ondeyka Debra;Qian Xiaoxia;Vachal Petr;Tyagarajan Sriram;Smith Cameron J.;Li Hong;Bao Jianming
分类号 A61K31/423;A61K31/4439;C07D413/14;A61K45/06;A61K31/506;A61K31/5377;C07D263/52;C07D413/06;A61K31/444 主分类号 A61K31/423
代理机构 代理人
主权项 1. A compound having formula I, or a pharmaceutically acceptable salt thereof, Wherein each R is independently H or —C1-C3alkyl; R1 is a cyclic substituent group connected to the oxazolidinone ring by a spirocyclic connection, wherein R1 is —C3-C8 cycloalkyl in which 1-2 carbons are optionally replaced by O, —NH—, —N(C1-C3alkyl)-, S, or —S(O)2—, wherein R1 is optionally substituted with 1-4 substituent groups which are halogen, —OH, —CN, —C1-C3 alkyl optionally substituted with 1-5 halogens, or —OC1-C3 alkyl optionally substituted with 1-5 halogens; A and B are each A1 or A2, wherein one of A and B is A1 and the other of A and B is A2, A1 has the structure: wherein D is selected from the group consisting of: (a) phenyl, and(b) HET(1); wherein ring D comprises at least two carbon atoms that are bonded to each other, wherein one of the two carbon atoms that are bonded to each other in ring D is connected to the group A3 and the other of the two carbon atoms that are bonded to each other in ring D is connected to the remainder of the structure of Formula I, so that A3 and the remainder of the structure of formula I are ortho to each other on ring D; A3 is (a) phenyl, or(b) HET(1), wherein A3 is optionally substituted with 1-5 substituent groups independently selected from Ra and optionally 1-2 groups X; HET(1) is a monocyclic 3-8-membered heterocyclic or heteroaromatic ring having 1-4 heteroatom groups independently selected from N, NH, S, O, —S(O)—, —S(O)2—, and —N(O)—, wherein HET(1) optionally comprises 1-4 double bonds and a carbonyl group; A2 is (a) phenyl,(b) HET(1), or(c) —C3-C8 cycloalkyl optionally having 1-3 double bonds; wherein A2 is optionally substituted with 1-5 substituent groups independently selected from Ra; Each Ra is independently selected from the group consisting of —C1-C6 alkyl, —C2-C6 alkenyl, —C2-C6 alkynyl, —OC1-C6alkyl, —OC2-C6alkenyl, —OC2-C6alkynyl, —C(═O)C1-C6alkyl, —C(═O)H, —OH, —NR6R7, —C(═O)NR6R7, —NR6C(═O)OC1-C6 alkyl, —NR6C(═O)NR6R7, —S(O)xC1-C6 alkyl, —S(O)yNR6R7, —NR6S(O)yNR6R7, —NR6S(O)yC1-C6 alkyl, halogen, —CN, —NO2, or HET(1), wherein HET(1) is optionally substituted with 1-3 substituent groups which are independently halogen, CH3, CF3, —OCH3, or —OCF3; wherein for compounds in which Ra is selected from the group consisting of —C1-C6 alkyl, —C2-C6 alkenyl, —C2-C6 alkynyl, —OC1-C6alkyl, —OC2-C6 alkenyl, —OC2-C6 alkynyl, —C(═O)C1-C6alkyl, —NR6C(═O)OC1-C6 alkyl, —S(O)xC1-C6 alkyl, and —NR6S(O)yC1-C6 alkyl, Ra is optionally substituted with 1-11 halogens; X is (a) C3-C8cycloalkyl which optionally comprises 1-2 double bonds and which is optionally substituted with 1-2 groups D1 and optionally with 1-5 substituent groups which are halogen, C1-C5 alkyl, —OC1-C5 alkyl, —CN, or —OH, wherein C1-C5 alkyl and —OC1-C5 alkyl are optionally substituted with 1-11 halogens and 1-2 groups —OH; (b) C1-C5 alkyl which is optionally substituted with 1-2 groups D1, optionally with 1-2 groups —OH, and optionally with 1-11 halogens; (c) phenyl which is optionally substituted with 1-2 groups D1 and optionally with 1-5 substituent groups which are halogen, C1-C5 alkyl, —OC1-C5 alkyl, —CN, or —OH, wherein C1-C5 alkyl and —OC1-C5 alkyl are optionally substituted with 1-11 halogens and 1-2 groups —OH; (d) HET1 which is optionally substituted with 1-2 groups D1 and optionally with 1-5 substituent groups which are halogen, C1-C5 alkyl, —OC1-C5 alkyl, —CN, or —OH, wherein C1-C5 alkyl and —OC1-C5 alkyl are optionally substituted with 1-11 halogens; or (e) D1; D1 is —CO2R8, —C(O)NR6R7, SO2NR6R7, or HET(1); R6 and R7 are each independently H or —C1-5alkyl; R8 is H or —C1-5alkyl optionally substituted with 1-7 halogens; p is an integer from 0-4; x is 0, 1, or 2; and y is 1 or 2.
地址 Rahway NJ US