| 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, or a linear or branched chain alkyl, alkylaryl, or hydroxyalkyl group, or an aryl group; R5, R6, R7, R8, and R9 are independently the same or different and are H, or a linear or branched chain alkyl, alkylaryl, alkoxy, hydroxyalkyl, or aminoalkoxy group, or an aryl or aryloxy group, or a C-glycal, or CO2R, nitro, cyano, Cl, F, Br, I, SR10, NR11R12, OR13; R is H, or a linear or branched chain alkyl, alkylaryl, or hydroxyalkyl group, or an aryl group; R10, R11 and R12 are independently the same or different and are H, or a linear or branched chain alkyl, alkylaryl, hydroxyalkyl, or acyl group, or an aryl group; 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. |