2. Academic Validation
  3. Synthesis of new camptothecin analogs with improved antitumor activities

Synthesis of new camptothecin analogs with improved antitumor activities

  • Bioorg Med Chem Lett. 2009 Apr 1;19(7):2018-21. doi: 10.1016/j.bmcl.2009.02.031.
Satoshi Niizuma 1,  Masao Tsukazaki,  Hitomi Suda,  Takeshi Murata,  Jun Ohwada,  Sawako Ozawa,  Hiroshi Fukuda,  Chikako Murasaki,  Masami Kohchi,  Kenji Morikami,  Kiyoshi Yoshinari,  Mika Endo,  Masako Ura,  Hiromi Tanimura,  Yoko Miyazaki,  Tsuyoshi Takasuka,  Akira Kawashima,  Eitaro Nanba,  Kounosuke Nakano,  Kotaro Ogawa,  Kazuko Kobayashi,  Hisafumi Okabe,  Isao Umeda,  Nobuo Shimma
Affiliations

Affiliation

  • 1 Kamakura Research Laboratories, Chugai Pharmaceutical Co., Ltd, 200 Kajiwara, Kamakura, Kanagawa 247-8530, Japan.
PMID: 19254843 DOI: 10.1016/j.bmcl.2009.02.031
Abstract

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.

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