New epothilone derivatives used for treating e.g. malignant melanoma, breast carcinoma, psoriasis, multiple sclerosis and arthritis

摘要

Epothilone derivatives (I) are new. Epothilone derivatives of formula (I) are new. R1a, R1b = H, 1-10C alkyl, 6-12C aryl or 7-20C aralkyl (all optionally substituted) or R1a + R1b = (CH2)m or (CH2)-O-(CH2); m = 1-5; R2a = H, 1-10C alkyl, 6-12C aryl or 7-20C aralkyl (all optionally substituted), (CH2)raC equivalent to C-(CH2)pa-R26a, (CH2)raCH=CH-(CH2)pa-R26a or a group of formula (i) or (ii); R2b = (CH2)rbC equivalent to C-(CH2)pb-R26a, (CH2)rbCH=CH-(CH2)pb-R26a or a group of formula (iii) or (iv); n = 0-5; ra, rb = 0-4; pa, pb = 0-3; R3a = H or 1-10C alkyl, 6-12C aryl or 7-20C aralkyl (all optionally substituted); R3b = OH or OPG14; PG14 = a protective group; R14 = H, OR14a or hal; R14a = H, SO2-alkyl, SO2-aryl or SO2-aralkyl; R4 = H, 1-10C alkyl, 6-12C aryl or 7-20C aralkyl (all optionally substituted), hal, OR25 or CN; R25 = H or a protective group PG5; R26a, R26b = H or 1-10C alkyl, 6-12C aryl or 7-20C aralkyl (all optionally substituted), 1-10C acyl or, if pa or pb is greater then 0, additionally OR27; R27 = H or a protective group PG6; R5 = H or 1-10C alkyl, 6-12C aryl, 7-20C aralkyl (all optionally substituted) or (CH2)s-T; s = 1-4; T = OR22 or hal; R22 = H or a protective group PG4; R6, R7 = H or R6 + R7 = an additional bond or O; G = X=CR8 or bi- or tri-cyclic aryl; R8 = H, hal, CN or 1-20C alkyl, 6-12C aryl, 7-20C aralkyl (all optionally substituted); X = O, 2 OR23 groups, 2-10C alkylene- alpha ,omega-dioxy, H/OR9 or CR10R11; R23 = 1-20C alkyl; R9 = H or protective group PGx; R10, R11 = H or 1-20C alkyl, 6-12C aryl or 7-20C aralkyl (all optionally substituted) or CR10R11 = 5-7 membered carbocyclyl; D-E = CH2-CH2 or O-CH2; A-Y = OCO, O-CH2, CH2CO, NR29CO or NR29-SO2; R29 = H or 1-10C alkyl; Z = O or H/OR12; R12 = H or protective group PGz and hal = halogen. An Independent claim is included for the preparation of (I).