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AssigneeResearch Triangle Institute
InventorsMonroe E. Wall, Mansukh C. Wani, Allan W. Nicholas, Govindarajan Manikumar
Estimating the term…
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 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.
A 20(S) or 20(RS)-camptothecin having the structure shown below:
A 20(S) or 20(RS)-camptothecin salt, wherein said salt has the structure shown below ##STR14## wherein Z is hydrogen or C.sub.1-8 alkyl 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--H.sub.2 CH.sub.2 CH.sub.2 N(CH.sub.2 CH.sub.2 CH.sub.2 OH.sub.2 .sub.2, O--, NH-- or S--H.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;
A method for preparing 9-nitro-10,11-methylenedioxy-20(S) or 20(RS)-camptothecin, comprising reacting 10,11-methylenedioxy 20(S) or 20(RS)- camptothecin with a mixture of concentrated sulfuric acid and concentrated nitric acid to obtain a product containing substantially 9-nitro-10,11-methylenedioxy-20(S)-- or 20(RS)-camptothecin.
A method for preparing 9-amino-10,11 methylenedioxy-20(S)- or 20(RS)-camptothecin, comprising the steps of nitrating 10,11-methylenedioxy-20(S)- or 20(RS)-camptothecin to obtain 9-nitro-10,11-methylenedioxy-20(S)- or 20(RS)-camptothecin, and then reducing the 9-nitro group of said 9-nitro-10,11-methylenedioxy-20(S)-- or 20(RS)-- or 20(RS)-camptothecin.
Dependencies are inferred from the claim text.