New, chemically and metabolically stable benzo-fused epothilon derivatives, useful e.g. for treating malignant tumors or chronic inflammatory disease, are cell division regulators

摘要

Epothilon derivatives (I), in which the macrocyclic ring is fused to a benzo ring, are new. Epothilon derivatives of formula (I), in which the macrocyclic ring is fused to a benzo ring, are new. R1a, R1b, R2a, R2b, R3a = H, 1-10C alkyl, aryl or 7-20C alkyl; or R1a + R1b, R2a + R2b = (CH2)n; or R1a + R1b = (CH2)2O(CH2)2; n = 2 - 5; E = phenylene, alkylene-phenylene or alkylene-phenylene-alkylene group of formula (a) or (b); t, w = 0-2; G, G' = H, halo, CN, R24, 1-20C acyl, 1-20C acyloxy, OR24, COOR24, N3, NO2, N(R24)2, pyrrolidino, piperidino or hexamethyleneimino; R24 = as R3a; R14 = H, OR14a or halo; R3b = OP'; R4a, R4b = H, 1-10C alkyl, aryl, 7-20C aralkyl or (CH2)sA; or R3b + R4a = bond; s = 1 - 4; A = OR22 or halo; R22 = H or P'; R6, R7 = H; or R6 + R7 = additional bond or O; R8 = H or F; or 1-20C alkyl, aryl or 7-20C aralkyl (all optionally substituted); X = O, (OR23)2, 2-10C alkylenedioxy, (H, OR9) or CR10R11; R23 = 1-20C alkyl; R9 = H or P'; R10, R11 = H, 1-20C alkyl, aryl or 7-20C aralkyl; or CR10R11 = 5-7 membered carbocycle; Y' = O or H2; Z' = O or (H, OR12); R12 = H or P'; and P' = protecting group. Independent claims are included for the preparation of (I).