New fredericamycin A derivatives with carbon-bonded B-ring substituent, are well tolerated topoisomerase I and/or II inhibitors especially useful for treating cancers or tumors

摘要

Fredericamycin A derivatives (I), carrying a C-bonded organic substituent in the B-ring, are new. Fredericamycin derivatives (I) of formula (Ia) or (Ib) (including stereoisomers and tautomers) and their salts and inclusion compounds are new. R1 : H, 1-6C alkyl, cycloalkyl or 1-4C alkyl-cycloalkyl; R2, R3 : 1-14C alkyl, 2-14C alkenyl, 1-4C alkylaryl, heteroaryl, 1-4C alkylheteroaryl, cycloalkyl, 1-4C alkyl-cycloalkyl, heterocycloalkyl, 1-4C alkyl-heterocycloalkyl, CHO, optionally esterified or amidated COOH or a wide range of specific substituted alkyl groups; R5, R6 : H, 1-14C alkyl, 2-14C alkenyl, aryl, 1-4C alkylaryl, heteroaryl, 1-4C alkylheteroaryl, cycloalkyl, 1-4C alkyl-cycloalkyl, heterocycloalkyl, 1-4C alkyl-heterocycloalkyl or various specific substituted alkyl groups; or together complete a 5-7 membered ring; R4, R7, R8 : H, 1-6C alkyl or a wide range of specific substituted carbonyl groups; X1, X2O, S, NH, N(1-8C alkyl) or N(cycloalkyl); Y1, Y2O or N(R5); and X2-R6 can be replaced by H if Y1 or Y2 = NR5; Y3O, S or NH. [Image] ACTIVITY : Cytostatic; Dermatological; Antiinflammatory; Antiparasitic; Immunosuppressive. MECHANISM OF ACTION : Topoisomerase I and/or II inhibitor.