OPTISCH REINE ANALOGE DER CAMPTOTHECINE

摘要

Camptothecin analogs (I) or 91 compounds (e.g. (5R)-5-ethyl-9-fluoro-5-hydroxy-4,5,13,15-tetrahydro-1H,3H-oxepino(3',4':6,7) indolizino(1,2-b)quinoline-3,15-dione or (5R)-5-ethyl-11-fluoro-5-hydroxy-4,5,13,15-tetrahydro-1H,3H-oxepino(3',4':6,7) indolizino(1,2-b)quinoline-3,15-dione) are new. Camptothecin analogs of formula (I) or 91 compounds (e.g. (5R)-5-ethyl-9-fluoro-5-hydroxy-4,5,13,15-tetrahydro-1H,3H-oxepino(3',4':6,7) indolizino(1,2-b)quinoline-3,15-dione or (5R)-5-ethyl-11-fluoro-5-hydroxy-4,5,13,15-tetrahydro-1H,3H-oxepino(3',4':6,7) indolizino(1,2-b)quinoline-3,15-dione) are new. R1 = lower alkyl; R2-R5 = H, halo or -OSO2R10; R6 = H, 1-12C alkyl (optionally substituted with at least one halo), lower hydroxyalkyl, lower alkoxy- lower alkyl, cycloalkyl, cycloalkyl- lower alkyl, nitro, halo, -(CH2)m-SiR7R8R9, aryl or aryl-lower alkyl (both optionally substituted on aryl with lower alkyl, OH, halo, amino, lower alkylamino, di(lower alkyl) amino, CF3 or OCF3); R7-R9 = lower alkyl; R10 = lower alkyl (optionally substituted with at least one halo) or aryl (optionally substituted with at least one lower alkyl); m = 0-6; and provided that R2 is H, when R6 is 7-12C alkyl, -(CH2)m-SiR7R8R9 or aryl substituted with di(lower alkyl)amino or OCF3, and/or when one of R3-R5 is -OSO2R10; or that one of R2-R5 is -OSO2R10 and/or R6 is 7-12C alkyl, -(CH2)m-SiR7R8R9 or aryl substituted with di(lower alkyl)amino or OCF3 and/or R2 is halo. Independent claims are also included for: (1) the preparation of (III); (2) a compound of formula (M); and (3) the preparation of (M). R'6 = 1-12C alkyl (optionally substituted with at least one halo), lower hydroxyalkyl, lower alkoxy- lower alkyl, cycloalkyl- lower alkyl, -(CH2)m-SiR7R8R9 or aryl-lower alkyl (optionally substituted on aryl with lower alkyl, OH, halo, amino, lower alkylamino, di(lower alkyl) amino, CF3 or OCF3).