| 摘要 |
Substituted 4-(1H-benzimidazol-2-yl)[1,4] diazepane compounds of formula (I) and their stereoisomers and salts are new. m = 2 or 3; n = 0 or 1; q = 1 or 2; r = 0 or 1; G1 = CH2 or CO; G2 = CH2, CHMe or CO; G3 = CH2 or CO; Ar1 = phenyl or naphthyl, both optionally substituted by R1, pyridinyl optionally substituted by R2, or thienyl; R1 = 1-3 of halo, OH, CF3, 1-6C alkyl and/or 1-6C alkoxy; R2 = 1 or 2 of halo, 1-6C alkyl and 1-6C alkoxy; Ar2 = phenyl optionally substituted by R21 and/or R3 or a group of formula (i); z = 1 or 2; R20 = 1 or 2 of H, OH, halo, 1-6C alkyl and 1-6C alkoxy; R3 = 1-3 of OH, halo, OCF3, 1-6C alkyl, 1-6C alkoxy, (CH2)dS(O)bR22, (CH2)eCN, O(CH2)cCO2R23, NH2, NHC(O)Me or NHSO2Me; c = 1-5; b = 0-2; d = 0 or 1; e = 0 or 1; R22 = 1-4C alkyl; R23 = H or 1-4C alkyl; R21 = 1,2,3,4-tetrazol-1-yl or 1,2,3,4-tetrazol-1-ylmethyl, both optionally 5-substituted by R24, 1,2,3,4-tetrazol-5-yl or 1,2,3,4-tetrazol-5-ylmethyl, imidazol-1-ylmethyl, 4,1,2-triazol-4-yl optionally 3,5-disubstituted by R25, or 1,2,4-triazol-1-ylmethyl;f = 0 or 1; R25 = Me; R24 = 1-4C alkyl, CF3, Ph, S(O)xR26 or CH2NMe2; x = 0-2; R26 = 1-4C alkyl; R4 = 1-3 of H, halo, CF3, 1-6C alkyl or 1-6C alkoxy; R5 = H, 1-4C alkyl, (CH2)wO(CH2)tCO2R8, (CH2)jCN, (CH2)uCO2R6, (CH2)uCONR16R17, (CH2)uCOMe, (CH2)pAr3, (CH2)wOR7, CH2CH=CHCF3, (CH2)2CH=CH2, CH2CH=CH2, CH2CH=CHMe, CH2CH=CHCH2Me, CH2CH=CMe2 or (CH2)gS(O)kR19; w = 2-5; t = 1-3; j, u = 1-5; p = 1-4; g = 2 or 3; k = 0-2; R6, R8 = H or 1-4C alkyl; R17,R16 = H or 1-4C alkyl; R19 = 1-4C alkyl or phenyl; Ar3 = phenyl optionally substituted by R9, pyridinyl optionally substituted by R10, furanyl optionally 2-substituted by R11, imidazol-2-yl optionally substituted by R12, thienyl optionally 2-substituted by R18, 1,2,4-triazol-1-yl, 1,2,3,4-tetrazol-5-yl, 1,2,3,4-tetrazol-1-yl, or imidazol-1-yl; R9 = 1-3 of halo,CF3, 1-6C alkyl, 1-6C alkoxy or CO2R13; R13 = H or 1-4C alkyl; R10 = 1 or 2 of halo, 1-6C alkyl or 1-6C alkoxy; R11 = Me or CH2OH; R12 = 1-4C alkyl or benzyl; R18 = halo, Me or CH2OH: R7 = H, 1-4C alkyl, (CH2)yCF3, CH2CN, phenyl optionally substituted by R14, or a group of formula (ii); v = 1-3; y = 0-2; R14 = halo, 1-4C alkyl or CO2R15; and R15 = H or 1-4C alkyl; provided that (i) when G1 = CO then G2 = CH2 or CHMe and G3 = CH2; (ii) when G2 = CO then G1 = CH2 and G3 = CH2; and (iii) when G3 = CO then G1 = CH2 and G2 = CH2 or CHMe. Also claimed is the intermediate (/|)-1-(2-chloro-3,4,5-trimethoxybenzoyl)-3-(2-(4-(1-(2-ethoxyethyl)-1H-benzimidazol-2-yl)[1,4]diazepan-1-yl)ethyl)-3-phenylpyrrolidine (II). |
