Fused bicyclic oxazolidinone CETP inhibitor

摘要

Compounds having the structure of Formula I, including pharmaceutically acceptable salts of the compounds, are CETP inhibitors and are useful for raising HDL-cholesterol, reducing LDL-cholesterol, and for treating or preventing atherosclerosis.;

主权项

1. A compound of Formula I, or a pharmaceutically acceptable salt thereof, wherein R1 is H, —C1-C5 alkyl, —OC1-C5 alkyl, —C2-C5 alkenyl, —OC2-C5 alkenyl, —C2-C5 alkynyl, —OC2-C5 alkynyl, —OH, halogen, —CN, —NR6R7, —CO2R8, —C(O)NR6R7, —SO2NR6R7, HET(3), or C3-6 cycloalkyl optionally having 1-2 double bonds, wherein —C1-C5 alkyl, —OC1-C5 alkyl, —C2-C5 alkenyl, —OC2-C5 alkenyl, —C2-C5 alkynyl, and —OC2-C5 alkynyl are each optionally substituted with 1-7 halogens, and wherein HET(3) and C3-6 cycloalkyl optionally having 1-2 double bonds are optionally substituted with 1-3 substituent groups which are each independently halogen, —C1-C3 alkyl, —OC1-C3 alkyl, —C2-C3 alkenyl, —OC2-C3 alkenyl, —C2-C3 alkynyl, or —OC2-C3 alkynyl, wherein —C1-C3 alkyl, —OC1-C3 alkyl, —C2-C3 alkenyl, —OC2-C3 alkenyl, —C2-C3 alkynyl, and —OC2-C3 alkynyl are each optionally substituted with 1-7 halogens; R6 and R7 are each independently H or —C1-C5 alkyl; R8 is H or —C1-5alkyl optionally substituted with 1-7 halogens; HET(3) is a 3-6 membered heterocyclic ring having 1-3 heteroatom groups which are each independently N, NH, O, S, S(O), or S(O)2 and optionally having 1-3 double bonds; x is 0 or 1; The dashed lines in Formula I represent one optional double bond between 2 adjacent carbon atoms; D1 is N or CR2; D2 is N or CR3; D3 is N or CR4; R2, R3, and R4 are each independently H, —C1-C5 alkyl, —OC1-C5 alkyl, —C2-C5 alkenyl, —OC2-C5 alkenyl, —C2-C5 alkynyl, —OC2-C5 alkynyl, —OH, halogen, —CN, —NR6R7, —CO2R8, —C(O) NR6R7, or —SO2NR6R7, wherein —C1 -C5 alkyl, —OC1-C5 alkyl, —C2-C5 alkenyl, —OC2-C5 alkenyl, —C2-C5 alkynyl, and —OC2-C5 alkynyl are optionally substituted with 1-7 halogens; Each R5 is independently —C1-C5 alkyl, —OC1-C5 alkyl, —C2-C5 alkenyl, —OC2-C5 alkenyl, —C2-C5 alkynyl, —OC2-C5 alkynyl, —OH, halogen, —CN, —NR6R7, —CO2R8, —C(O) NR6R7, or —SO2NR6R7, wherein —C1-C5 alkyl, —OC1-C5 alkyl, —C2-C5 alkenyl, —OC2-C5 alkenyl, —C2-C5 alkynyl, and —OC2-C5 alkynyl are optionally substituted with 1-7 halogens; A1 is phenyl, HET(1), or C3-C8 cycloalkyl optionally having 1-2 double bonds, wherein A1 is optionally substituted with one substituent group Z and is optionally substituted with 1-3 groups which are each independently —C1-C5 alkyl, —OC1-C5 alkyl, —C2-C5 alkenyl, —OC2-C5 alkenyl, —C2-C5 alkynyl, —OC2-C5 alkynyl, halogen, —OH, or —CN, wherein —C1-C5 alkyl, —OC1-C5 alkyl, —C2-C5 alkenyl, —OC2-C5 alkenyl, —C2-C5 alkynyl, and —OC2-C5 alkynyl are optionally substituted with 1-7 halogens; Each HET(1) is a 5- or 6-membered heterocyclic ring having 1-4 heteroatom groups which are each independently —N—, —NH—, —S—, —O—, —S(O)—,or —S(O)2—, optionally having one group —C(═O)—, and optionally having 1-3 double bonds; Z is A3, —C1-C3alkylene-CO2R8, —C1-C3alkylene-C(O)NR6R7, —C1-C3alkylene-SO2NR6R7, —CO2R8, —C(O)NR6R7, —SO2NR6R7, or —C1-C3alkylene-HET(2), wherein —C1-C3alkylene in all uses is optionally substituted with 1-7 halogens, and HET(2) is optionally substituted with 1-3 substituents which are independently —C1-3alkyl optionally substituted with 1-5 halogens, —OC1-3alkyl optionally substituted with 1-5 halogens, halogen or NR6R7; A3 is phenyl, C3-C6 cycloalkyl optionally having 1-2 double bonds, or HET(1), wherein A3 is optionally substituted with 1-3 groups which are each independently —C1-C5 alkyl, —OC1-C5 alkyl, —C2-C5 alkenyl, —OC2-C5 alkenyl, —C2-C5 alkynyl, —OC2-C5 alkynyl, halogen, —OH, or —CN, wherein —C1-C5 alkyl, —OC2-C5 alkyl, —C2-C5 alkenyl, —OC2-C5 alkenyl, —C2-C5 alkynyl, and —OC2-C5 alkynyl are optionally substituted with 1-7 halogens; and A3 is optionally substituted with one group which is HET(2), —C1-4 alkylene-CO2R8, —C1-4alkylene-C(O)NR6R7, —C1-C4alkylene-SO2NR6R7, —CO2R8, —C(O)NR6R7, or —SO2NR6R7, wherein —C1-C4alkylene in all uses is optionally substituted with 1-7 halogens; and wherein HET(2) is optionally substituted with 1-3 groups which are each independently halogen, —C1-5alkyl optionally substituted with 1-7 halogens, —OC1-5alkyl optionally substituted with 1-7 halogens, or NR6R7; HET(2) is a 5-6 membered heterocyclic ring having 1-3 heteroatom groups which are each independently N, NH, O, or S, optionally having one group —C(═O)—, and optionally having 1-3 double bonds; A2 is phenyl or HET(1), wherein A2 is optionally substituted with 1-3 substituent groups which are each independently —C1-C5 alkyl, —OC1-C5 alkyl, —C2-C5 alkenyl, —OC2-C5 alkenyl, —C2-C5alkynyl, —OC2-C5alkynyl, halogen, —CN, —OH, or C3-6cycloalkyl, wherein —C1-C5 alkyl, —OC1-C5 alkyl, —C2-C5 alkenyl, —OC2-C5 alkenyl, —C2-C5alkynyl, and —OC2-C5 alkynyl are optionally substituted with 1-7 halogens, and C3-6cycloalkyl is optionally substituted with 1-3 substituents which are each independently halogen, —C 1-C3 alkyl, or —OC1-C3 alkyl, wherein —C1-C3 alkyl and —OC1-C3 alkyl are each optionally substituted with 1-7 halogens; and a is 0 or an integer from 1-3.