Methods of preparation of camptothecin analogs

Details Methods of preparation of camptothecin analogs Methods of preparation of camptothecin analogs

1993-01-11

1995-02-21

Dentz, Bernard

Organic compounds -- part of the class 532-570 series

Organic compounds

Heterocyclic carbon compounds containing a hetero ring...

546 92, C07D49152, C07D491147

Patent

active

053917456

ABSTRACT:
Substituted analoguss 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, or a linear or branched chain alkyl, alkylaryl, or hydroxyalkyl group, or an aryl group; 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, or a linear or branched chain alkyl, alkylaryl, alkoxy, hydroxyalkyl, or aminoalkoxy group, or an aryl or aryloxy group, or a C-glycal, or CO.sub.2 R, nitro, cyano, Cl, F, Br, I, SR.sup.10, NR.sup.11 R.sup.12, or OR.sup.13 ; R is H, or a linear or branched chain alkyl, alkylaryl, or hydroxyalkyl group, or an aryl group; R.sup.10, R.sup.11 and R.sup.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.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 analoguss involve condensation of such intermediates with variably substituted protected .alpha.-aminobenzaldehydes.

REFERENCES:
patent: 3894029 (1975-07-01), Winterfeldt et al.
patent: 4031098 (1977-06-01), Sugasawa
patent: 4399282 (1983-08-01), Miyasaka et al.
patent: 4473692 (1984-09-01), Miyasaka et al.
patent: 4513138 (1985-04-01), Miyasaka et al.
patent: 4545880 (1985-10-01), Miyasaka et al.
patent: 4604463 (1986-08-01), Miyasaka et al.
patent: 4894456 (1990-01-01), Wall et al.
patent: 4914205 (1990-04-01), Sawada et al.
patent: 4939255 (1990-07-01), Tagawa et al.
patent: 4943579 (1990-07-01), Vishnuvajjala et al.
patent: 4981968 (1991-01-01), Wall et al.
patent: 5004758 (1991-04-01), Boehm et al.
patent: 5049668 (1991-09-01), Wall et al.
patent: 5061795 (1991-10-01), Tagawa et al.
patent: 5061800 (1991-10-01), Yaegashi et al.
patent: 5106742 (1992-04-01), Wall et al.
patent: 5122526 (1992-06-01), Wall et al.
Danishefsky, S., and Etheredge, S. J., Synthesis And Biological Evaluation of De-AB Camptothecin, J. Org. Chem., 39:3430-3432 (1974).
Giovanella, B. C., et al., DNA Topoisomerase I-Targeted Chemotherapy of Human Colon Cancer in Xenografts, Science, 246:1046-1048 (1989).
Hsiang, Y.-H., et al., Camptothecin Induces Protein-linked DNA Breaks Via Mammalian DNA Topoisomerase I, J. Biol. Chem., 260:14873-14878 (1985).
Hsiang, Y.-H., and Liu, L. F., Identification of Mammalian DNA Topoisomerase I as An Intracellular Target Of The Anticancer Drug Camptothecin, Cancer Research, 48:1722-1726 (1988).
T. Kunimoto, et al., Antitumor Activity of 7-Ethyl-10-[4-(1-piperidine)-1-piperidine]-carbonyloxy-camptothecin, A Novel Water-soluble Derivative of Camptothecin, Against Murine Tumors, Cancer Research, 47:5944-5947 (1987).

Affiliated with

Also associated with

Rating

Methods of preparation of camptothecin analogs does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Methods of preparation of camptothecin analogs, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Methods of preparation of camptothecin analogs will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-1931388