| abstract |
Substituted analogues of camptothecin possessing cytotoxic activity towards cancer cells, of the general structure: <IMAGE> wherein E is H, CO2R, CONH2, CONHR, CONR2, acyl, or CN; X is H, OH, or OR; R1, R2, R3, and R4 are independently the same or different and are H, linear or branched alkyl, linear or branched alkylaryl, hydroxyalkyl, or aryl; R5, R6, R7, R8, and R9 are independently the same or different and are H, linear or branched alkyl, linear or branched alkylaryl, aryl, CO2R, alkoxy, aryloxy, hydroxyalkyl, C-glycal, nitro, cyano, aminoalkoxy, Cl, F, Br, I, SR10, NR11R12, or OR13; R is H, alkyl, aryl, alkylaryl, hydroxyalkyl, or hydroxyalkyl; R10, R11 and R12 are independently the same or different and are H, alkyl, aryl, alkylaryl, hydroxyalkyl, or acyl; R13 is glycosyl; n is 0 or 1; with the proviso that when R1 is ethyl, and n is 0, E, R2, R3, and R4 are not all H. Intermediate compounds leading to the camptothecin analogues comprise substituted tricyclic compounds which consist of rings C, D, and E fused together. Methods for preparing the analogues involve condensation of such intermediates with variably substituted protected alpha -aminobenzaldehydes. |