Heterocyclic condensed pyridines as CETP inhibitors

摘要

Condensed pyridine derivatives of formula (I), and their salts and N-oxides, are new. A = 6-10C aryl (optionally mono- to penta-substituted by halo, OH, CF3, OCF3, NO2, 1-7C alkyl, acyl, hydroxyalkyl or alkoxy, or NR3R4; D = XR5or C(R6)(R7)R8; R5, R6 = 3-8C cycloalkyl, 6-10C aryl, or 5-7 membered heteroaromatic (optionally benzocondensed containing up to 3 heteroatoms from N, O, S), (optionally mono- to penta- substituted by CF3, NO2, OCF3, halo, OH, COOH, 1-6C alkyl, acyl, alkoxy or alkoxycarbonyl, or Ar, OAr or SAr), where the rings are optionally substituted by NR9R10; Ar = phenyl optionally substituted by halo, CF3 or OCF3; X = 1-8C alkylene or alkenylene optionally mono- - di-substituted by OH; R7 = H or halo; R8 = H, halo, N3, CF3, OCF3, OH, 1-5C alkoxy or NR11R12; or R7+R8 = O; R3, R4, R9-R12 = H, phenyl or 1-6C alkyl; E = 3-8C cycloalkyl, or 1-8C alkyl (optionally substituted by 3-8C cycloalkyl or OH); R1+R2 = heterocyclic ring (formed from 1-6C alkylene, interrupted by O, S, SO2 or NR13, and optionally benzocondensed and containing a double bond) which is substituted by CO, OR14 or a group of formula (a), and optionally mono- to penta- substituted by 1-6C alkoxy or alkoxycarbonyl, CF3, halo, OH, carbonyl, Ar1, and/or optionally mono- to hexa- substituted by 3-8C cycloalkyl or cycloalkoxy, 1-6C alkyl (optionally substituted by OH, CF3, phenyl or 1-5C alkoxy) and/or optionally substituted by a spiro-residue of formula (b), (c) or (d); a = 1-3; Ar1 = phenyl (optionally substituted by halo, CF3, NO2, OH, or 1-6C alkoxy or alkoxycarbonyl); R13 = H, 1-6C alkyl, 1-6C acyl, or benzyl or phenyl (both optionally mono- or di-substituted by halo, OH, NO2, CF3, 1-6C alkyl or 1-6C acyl); R14 = H, 1-6C alkyl, 1-6C hydroxyalkyl, 1-6C acyl, ≤ 6C alkoxycarbonyl or SiR15R16R17; R15-R17 = phenyl or 1-6C alkyl; W = O or S; Y = 2-6C alkylene; c = 1-7; d = 1-2; R18-R24 = H, CF3, phenyl, halo, 1-6C alkyl or alkoxy; or R18+R19 or R20+R21 = 1-6C alkylene or W(CH2)fW; and f = 2-8.