New cripowellin derivatives useful in the preparation of medicament for the treatment of cancer or other proliferative diseases

摘要

Cripowellin derivatives (I) and (II) are new. Cripowellin derivatives of formulae (I) and (II) are new. R : H or -OR 1>; R-a : H or OH; either R 1>H, 2-tetrahydropyranyl, optionally substituted glycosyl, -SO 2R-4a, -COR-4a, -CO 2R-4a, -CONHR-4a, or -CONR-4aR-5a; and R 2>H, 2-tetrahydropyranyl, optionally substituted glycosyl, -SO 2R-4b, -COR-4b, -CO 2R-4b, -CONHR-4b or -CONR-4bR-5b; R 3>H, 2-tetrahydropyranyl, optionally substituted glycosyl, SO 2R-4c, -COR-4c, -CO 2R-4c, -CONHR-4c or -CONR-4cR-5c; or R 1>+R 3>carbonyl, thiocarbonyl or alkylene (optionally substituted by CH 3); R-4a-c, R-5a-c : alkyl (optionally substituted by halo) or optionally substituted aryl; Y 1>X = (R 6>)(CH 2)-C=C(R 7>)(CH 2), CH 3-N=C(R 6>)(CH 2), CH 3-N-(R 7>)(CH 3) or CH 3-N=N-CH 3; either R 6>, R 7>aryl, aryl-1-4C-alkyl, aryloxy, aryl-1-4C-alkyloxy, heteroaryl, hetaryloxy, heteroaryl-1-4C-alkyl, heteroaryl-1-4C-alkylolxy (all optionally substituted), H, halo, OH, NO 2, CN, NR 8>R 9>, SO 2OH, SO 2NR 8>R 9>, formyl, COOH, CONR 8>R 9>, (halo)-1-4C-alkyl, (halo)-1-4C-alkylcarbonyl, (halo)-1-4C-alkoxy, 1-4C-alkoxycarbonyl, (halo)-1-4C-alkylthio, (halo)-1-4C-alkylsulfinyl, (halo)-1-4C-alkylsulfonyl, 1-4C-alkyloxysulfonyl or 3-7C-cycloalkyl; or R 6>+R 7> = O-CH 2-O-, -O-CHF-O-, -O-CF 2-O-, -O-CH 2-CH 2-O- or -O-CF 2-CF 2-O-; either R 8>, R 9>H, halo-1-4C-alkyl, halo-1-4C-alkylcarbonyl,1-4C-alkoxy, 1-4C- alkoxycarbonyl, 1-4C-alkylsulfinyl, 1-4C-alkylsulfonyl, 3-7C-cycloalkyl, 3-7C-cycloalkylcarbonyl, 3-7C-cycloalkyl-1-2C-alkyl or phenyl-1-2C-alkyl; or NR 8>R 9>5-6 membered ring (optionally substituted by heteroatoms); A : CH 2, carbonyl, thiocarbonyl or -CH(OR 2>); B 1>CH 2, carbonyl, thiocarbonyl or -CH(OR 3>); and Q : O or S. An independent claim is included for the preparation of (I) and (II). [Image] ACTIVITY : Cytostatic. MECHANISM OF ACTION : None given.