New 9-oxa-epothilone derivatives, are phase-specific cell division regulators useful for treating malignant tumors, angiogenesis or inflammatory disease

摘要

9-Oxa-epothilone derivatives (I) are new. Epothilone derivatives of formula (I) are new. R1a, R1b = H, 1-10C alkyl, aryl or 7-20C aralkyl; R1a + R1b = (CH2)m or CH2OCH2; or m = 1-5; R2a, R2b = H, 1-10C alkyl, aryl, 7-20C aralkyl, -(CH2)r-CC-(CH2)p-R9 or -(CH2)r-CH=CH-(CH2)p-R9; r = 0-4; p = 0-3; R9 = H, 1-10C alkyl, aryl, 7-20C aralkyl or 1-10C acyl; or may also be OR10 if p is other than 0; R10 = H or P'; P' = protecting group; R3a, R4 = H, 1-10C alkyl, aryl or 7-20C aralkyl; R3b = OH or OP'; R5 = H, 1-10C alkyl, aryl, 7-20C aralkyl, halo, CN or (CH2)sT; s = 1-4; T = OR11 or halo; R11 = H or P'; R6, R7 = H; or together form an additional bond or O; G = -C(X)-R12 or bi- or tricyclic aryl; R12 = H, halo or CN; or 1-20C alkyl, aryl or 7-20C aralkyl (all optionally substituted); X = O, (OR13)2, optionally branched 2-10C alkylene- alpha ,w-dioxy, H/OR14 or CR15R16; R13 = 1-20C alkyl; R14 = H or P'; R15, R16 = H, 1-10C alkyl, aryl or 7-20C aralkyl; A-Y = OC(O), OCH2, CH2C(O), NR17C(O) or NR17SO2; R17 = H or 1-10C alkyl; Z' = O or H/OR18; R18 = H or P'; R8 = OH or OP'; excluded are (I; R2a = H; R2b, R5 = H, alkyl or aryl; A-Y = OC(O), OCH2 or NR17C(O)).