SUBSTITUTED BISINDOLYLMALEIMIDES FOR THE INHIBITION OF CELL PROLIFERATION

摘要

Compounds of formula (I) wherein: R?1 and R1'¿ are independently alkyl, aryl, alkenyl or alkynyl; R?2 and R2'¿ are independently hydrogen, alkyl, aralkyl, alkoxyalkyl, hydroxyalkyl, haloalkyl, aminoalkyl, monoalkylaminoalkyl, dialkylaminoalkyl, acylaminoalkyl, alkylsulphonylaminoalkyl, arylsulphonyl-aminoalkyl, mercaptoalkyl, alkylthioalkyl, carboxyalkyl, alkoxycarbonylalkyl, aminocarbonylalkyl, alkylthio or alkylsulphinyl; R?4, R5, R6, R7, R4', R5', R6' and R7'¿ each independently are hydrogen, formula (II), CO¿2R?9, CH2OR10, CHO, CH¿2?NR?11R12, CON(R13)¿2, halogen, cyano, aryl, alkyl, hydroxy, alkoxy, aryloxy, haloalkyl, nitro, amino, aralkyloxy, acylamino, monoalkylamino, dialkylamino, thio, alkylthio, alkylsulphinyl, alkylsulphonyl, arylsulphinyl, azide, phosphate or phosphonate provided that at least one of R?4, R5, R6 and R7¿ and at least one of R?4', R5', R6' and R7'¿ are other than hydrogen, with the proviso that when R6 is methoxy, R?5 or R5'¿ are not methoxy; R8 is alkyl or aryl; R9 is alkyl or aryl; R10 is hydrogen, alkyl or aryl; R?11 and R12¿ are independently hydrogen, alkyl, aryl, aralkyl or acyl; R13 is hydrogen, alkyl, aryl or aralkyl; and one of X and Y signifies O and the other signifies O, S, (H,OH) or (H,H); as well as pharmaceutically acceptable prodrugs therefor or pharmaceutically acceptable salts of acidic compounds of formula (I) with basis or basic compounds of formula (I) with acids are antiproliferative agents useful in the treatment of cancer.