Camptothecin analogues

Details Camptothecin analogues Camptothecin analogues

1992-07-23

1995-08-29

Dentz, Bernard

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Having -c-, wherein x is chalcogen, bonded directly to...

546 48, A61K 31435, C07D49122

Patent

active

054460476

ABSTRACT:
Substituted analogues of camptothecin possessing cytotoxic activity towards cancer cells, of the general structure: ##STR1## wherein E is H, CO.sub.2 R, CONH.sub.2, CONHR, CONR.sub.2, acyl, or CN; X is H, OH, or OR; R.sup.1, R.sup.2, R.sup.3, and R.sup.4 are independently the same or different and are H, linear or branched alkyl, linear or branched alkylaryl, hydroxyalkyl, or aryl; R.sup.5, R.sup.6, R.sup.7, R.sup.8, and R.sup.9 are independently the same or different and are H, linear or branched alkyl, linear or branched alkylaryl, aryl, CO.sub.2 R, alkoxy, aryloxy, hydroxyalkyl, C-glycal, nitro, cyano, aminoalkoxy, Cl, F, Br, I, SR.sup.10, NR.sup.11 R.sup.12, or OR.sup.13 ; R is H, alkyl, aryl, alkylaryl, hydroxyalkyl, or hydroxyalkyl; R.sup.10, R.sup.11 and R.sup.12 are independently the same or different and are H, alkyl, aryl, alkylaryl, hydroxyalkyl, or acyl; R.sup.13 is glycosyl; n is 0 or 1; with the proviso that when R.sup.1 is ethyl, and n is 0, E, R.sup.2, R.sup.3, and R.sup.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.

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