CAMPTOTHECIN ANALOGUES AND METHODS OF PREPARATION THEREOF

摘要

Substituted analogues of camptothecin possessing cytotoxic activity towards cancer cells, of general structure (I), wherein E is H, CO2R, CONH2, CONHR, CONR2, acyl, or CN; X is H, OH, or OR; R<1>, R<2>, R<3> and R<4> are independently the same or different and are H, or a linear or branched chain alkyl, alkylaryl, or hydroxyalkyl group, or an aryl group; R<5>, R<6>, R<7>, R<8> and R<9> 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, SR<10>, NR<11>R<12>, or OR<13>; R is H, or a linear or branched chain alkyl, alkylaryl, or hydroxyalkyl group, or an aryl group; R<10>, R<11> and R<12> 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; R<13> is glycosyl; n is 0 or 1; with the proviso that when R<1> is ethyl, and n is 0, E, R<2>, R<3> and R<4> 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.