Research Triangle Institute

Other

Johns Hopkins University

Monroe E Wall

Mansukh C Wani

Govindarajan Manikumar

Allan W Nicholas

Dolatrai M Vyas

Neelakantan Balasubramanian

Yves Pommier

Robert E Miller

Theresa A Shapiro

David J Adams

Michael P Gamcsik

O Michael Colvin

Annette L Bodley

Robert R Engle

Camptothecin compounds which are effective anti-tumor compounds are disclosed. These conjugates inhibit the enzyme topoisomerase I and enhance the stability of the topoisomerase I-DNA cleavable complex.

Camptothecin compounds with a thioether group

&bgr;-Alanine esters of camptothecin compounds which are effective anti-tumor compounds are disclosed. These compounds inhibit the enzyme topoisomerase I and may alkylate DNA of the associated topoisomerase I-DNA cleavable complex.

Camptothecin &bgr;-alanine esters with topoisomerase I inhibition

Camptothecin compounds having a C,O&mdash;(CF,),O group where n is 1 or 2 are effective anti-tumor compounds. These compounds inhibit the enzyme topoisomerase I and may alkylate DNA of the associated topoisomerase I-DNA cleavable complex.

10, 11-difluoromethylenedioxycamptothecin compounds with topoisomerase I inhibition

Non-toxic camptothecin prodrugs are prepared by esterifying the 20-position hydroxyl group of camptothecin derivatives.

Water-soluble esters of camptothecin compounds

Camptothecin compounds having a --CH.sub.2 --L group are effective anti-tumor compounds. These compounds inhibit the enzyme topoisomerase I and DNA of associated topoisomerase I-DNA complexes.

Camptothecin compounds with combined topoisomarase I inhibition and DNA

Camptothecin compounds with combined topoisomerase I inhibition and DNA

Camptothecin compounds are effective inhibitors of plasmodia growth and are useful in treating plasmodia infections in livestock, other domestic animals and humans.

Inhibition of plasmodia parasites by camptothecin compounds

Camptothecin compounds are effective inhibitors of hemoflagellate growth and are useful in treating leishmaniasis and trypanosomiasis in livestock, other domestic animals and humans.

Inhibition of hemoflagellates by camptothecin compounds

A method for synthesizing camptothecin and camptothecin analogs using a novel hydroxyl-containing tricyclic intermediate and the camptothecin analogs produced by the process. The camptothecin analogs are effective inhibitors of topoisomerase. I and show antileukemic and anti-tumor activity.

Alkyl camptothecin compounds as potent inhibitors of human colorectal

A method for synthesizing camptothecin and camptothecin analogs using a novel hydroxyl-containing tricyclic intermediate and the camptothecin analogs produced by the process. The camptothecin analogs are effective inhibitors of topoisomerase.I and show antileukemic and anti-tumor activity.

Camptothecin analogs as potent inhibitors of topoisomerase I

A camptothecin analog having the structure shown below: ##STR1## where Z is H or C.sub.1-8 alkyl and R is NO.sub.2, NH.sub.2, N.sub.3, hydrogen, halogen, COOH, OH, O-C.sub.1-3 alkyl, SH, S-C.sub.1-3 alkyl, CN, CH.sub.2 NH.sub.2, NH-C.sub.1-3 alkyl, CH.sub.2 -NH-C.sub.1-3 alkyl, N(C.sub.1-3 alkyl).sub.2, CH.sub.2 N(C.sub.1-3 alkyl).sub.2, O-, NH- or S-CH.sub.2 CH.sub.2 N(CH.sub.2 CH.sub.2 OH).sub.2, O-, NH- or S- CH.sub.2 CH.sub.2 CH.sub.2 N(CH.sub.2 CH.sub.2 OH).sub.2, O-, NH- or S-CH.sub.2 CH.sub.2 N(CH.sub.2 CH.sub.2 CH.sub.2 OH).sub.2, O-, NH- or S-CH.sub.2 CH.sub.2 CH.sub.2 N(CH.sub.2 CH.sub.2 OH.sub.2).sub.2, O-, NH- or S-CH.sub.2 CH.sub.2 N(C.sub.1-3 alkyl).sub.2, O-, NH- or S-CH.sub.2 CH.sub.2 CH.sub.2 N(C.sub.1-3 alkyl).sub.2, CHO, C.sub.1-3 alkyl or NHCOCHR.sup.1 NR.sup.2 R.sup.3, where R.sup.1 is the side-chain of an .alpha.-amino acid and R.sup.2 and R.sup.3, independently are hydrogen or a lower alkyl group or R.sup.3 is a peptide unit containing 1-3 amino acid units bonded to the nitrogen through a peptide bond; NHCO-C.sub.2-8 -alkylene-X or NHCO-C.sub.2-8 -alkenylene-X, where X is COOH; CONR.sup.2 -(CH.sub.2).sub.n -NR.sup.2 R.sup.3, where n=1-10 and R.sup.2 and R.sup.3 are as defined above; NHCO-B-(CH.sub.2).sub.n-NR.sup.2 R.sup.3, where B=oxygen or NH, or ##STR2## where m+y=3-6, and salts thereof. The campothecin compounds inhibit the enzyme topisomerase I and are useful in treating tumors and leukemia.

Method of treating tumors with anti-tumor effective camptothecin

A method for synthesizing camptothecin analogs using a novel hydroxyl-containing tricyclic intermediate and the camptothecin analogs produced by the process. The camptothecin analogs are effective inhibitors of topoisomerase.

A method for synthesizing camptothecin and camptothecin analogs using a novel hydroxyl-containing tricyclic intermediate and the camptothecin analogs produced by the process. The camptothecin analogs are effective inhibitors of topoisomerase I and show antileukemic and anti-tumor activity.

Growing community of inventors

Chapel Hill, NC, United States of America

Monroe E Wall