Synthesis of new camptothecin analogs with improved antitumor activities
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...
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| Veröffentlicht in: | Bioorganic & medicinal chemistry letters 2009-04, Vol.19 (7), p.2018-2021 |
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| container_title | Bioorganic & medicinal chemistry letters |
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| creator | NIIZUMA, Satoshi TSUKAZAKI, Masao YOSHINARI, Kiyoshi ENDO, Mika URA, Masako TANIMURA, Hiromi MIYAZAKI, Yoko TAKASUKA, Tsuyoshi KAWASHIMA, Akira NANBA, Eitaro NAKANO, Kounosuke OGAWA, Kotaro SUDA, Hitomi KOBAYASHI, Kazuko OKABE, Hisafumi UMEDA, Isao SHIMMA, Nobuo MURATA, Takeshi OHWADA, Jun OZAWA, Sawako FUKUDA, Hiroshi MURASAKI, Chikako KOHCHI, Masami MORIKAMI, Kenji |
| description | 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. |
| doi_str_mv | 10.1016/j.bmcl.2009.02.031 |
| format | Article |
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| fulltext | fulltext |
| identifier | ISSN: 0960-894X |
| ispartof | Bioorganic & medicinal chemistry letters, 2009-04, Vol.19 (7), p.2018-2021 |
| issn | 0960-894X 1464-3405 |
| language | eng |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Animals Antineoplastic agents Antineoplastic Agents - chemical synthesis Antineoplastic Agents - chemistry Antineoplastic Agents - pharmacology Biological and medical sciences Camptothecin - analogs & derivatives Camptothecin - chemical synthesis Camptothecin - chemistry Camptothecin - pharmacology Cell Line, Tumor DNA Topoisomerases, Type I - metabolism General aspects Humans Medical sciences Mice Pharmacology. Drug treatments Structure-Activity Relationship Topoisomerase I Inhibitors Transplantation, Heterologous |
| title | Synthesis of new camptothecin analogs with improved antitumor activities |
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