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Synthesis of new camptothecin analogs with improved antitumor activities

Journal:
Bioorganic & Medicinal Chemistry Letters


Issue Date:
2009


Abstract(summary):

Novel hexacyclic camptothecin analogs containing cyclic amidine, urea, or thiourea moiety were designed and synthesized based on the proposed 3D-structure of the topoisomerase I (Topo I)/DNA/camptothecin ternary complex. The analogs were prepared from 9-nitrocamptothecin via 7,9-diaminocamptothecin derivatives as a key intermediate. Among them, 7c exhibited in vivo antitumor activities superior to CPT-11 in human cancer xenograft models in mice at their maximum tolerated doses though its in vitro antiproliferative activity was comparable to SN-38 against corresponding cell lines. (C) 2009 Elsevier Ltd. All rights reserved.


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2018---2021


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