104195-62-2Relevant academic research and scientific papers
7-Substituted camptothecin and camptothecin analogs and methods for producing the same
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Page 4, (2008/06/13)
Methods of forming 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.
Plant Antitumor Agents. 30. Synthesis and Structure Activity of Novel Camptothecin Analogs
Wall, Monroe E.,Wani, Mansukh C.,Nicholas, Allan W.,Manikumar, Govindarajan,Tele, Chhagan,et al.
, p. 2689 - 2700 (2007/10/02)
A large number of camptothecin (CPT) analogs have been prepared in the 20S, 20RS, and 20R configurations with a number of ring A substituents.Topoisomerase I (T-I) inhibition data (IC50) have been obtained by standard procedures.In general, substitution at the 9 or 10 positions with amino, halogeno, or hydroxyl groups in compounds with 20S configuration results in compounds with enhanced T-1 inhibition.Compounds in the 20RS configuration were less active in vitro and in vivo and those in the 20R configuration were inactive.Compounds with 10,11-methylenedioxy substitution on ring A displayed a marked increase in potency in the T-I inhibition assay.The activities of some of the analogs as determined in a variety of in vivo assays including the L-1210 mouse leukemia assay were, in general, in accord with T-I inhibition.A number of water-soluble analogs such as 20-glycinate esters, 9-glycinamides, or hydrolyzed lactone salts were prepared and tested in in vitro and in vivo assays.In general, these compounds were less active than CPT both in terms of T-I inhibition and life prolongation in the L-1210 assay.However, certain 20-glycinate esters showed good in vivo activity after iv administration.
Camptothecin derivatives and process for preparing same
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, (2008/06/13)
New Camptothecin derivatives possessing high anti-tumor activity with slight toxicity, represented by the general formula: STR1 wherein R1 is a hydrogen atom, an alkyl group, a hydroxyl group, an alkoxy group or an acyloxy group, R2 for a hydrogen atom, an alkyl group, an aralkyl group, a hydroxymethyl group, a carboxymethyl group or an acyloxymethyl group, and R3 is the grouping --XR' (where R' is a hydrogen atom, an alkyl group or an acyl group and X is an oxygen atom or a sulfur atom), a nitro group, an amino group, an alkylamino group, an acylamino group or a halogen atom, with the proviso that when both of R1 and R2 are hydrogen atoms, R3 should not be a hydroxyl group, methoxy group or acetoxy group. These new camptothecin derivatives are prepared by treating a 5-R1 -7-R2 -camptothecin derivative with a peroxidant and then reacting the resultant 5-R1 -7-R2 -camptothecin-1-oxide with an active hydrogen compound under irradiation of UV-rays or by catalytically hydrogenating the ring B of camptothecin in a solvent, treating the resultant tetrahydro product with an acylating agent, introducing a nitro group into the 10-position of the acylated product by the reaction with nitric acid, splitting off the acyl group in the 10-nitro product by hydrolysis and treating the hydrolyzed tetrahydro product with an oxidizing agent for dehydrogenation, and if desired, reducing the nitro group in the resulting product to an amino group and modifying the amino group by N-alkylation, N-acylation or by diazotization followed by hydrolysis or the Sandmeyer reaction, before or after the oxidation of the 10-nitro-tetrahydro product.
