Synthesis of new camptothecin analogs with improved antitumor activities

被引：21

作者：

Niizuma, Satoshi ^{[1
]}

Tsukazaki, Masao ^{[1
]}

Suda, Hitomi ^{[1
]}

Murata, Takeshi ^{[1
]}

Ohwada, Jun ^{[1
]}

Ozawa, Sawako ^{[1
]}

Fukuda, Hiroshi ^{[1
]}

Murasaki, Chikako ^{[1
]}

Kohchi, Masami ^{[1
]}

Morikami, Kenji ^{[1
]}

Yoshinari, Kiyoshi ^{[1
]}

Endo, Mika ^{[1
]}

Ura, Masako ^{[1
]}

Tanimura, Hiromi ^{[1
]}

Miyazaki, Yoko ^{[1
]}

Takasuka, Tsuyoshi ^{[1
]}

Kawashima, Akira ^{[1
]}

Nanba, Eitaro ^{[1
]}

Nakano, Kounosuke ^{[1
]}

Ogawa, Kotaro ^{[1
]}

Kobayashi, Kazuko ^{[1
]}

Okabe, Hisafumi ^{[1
]}

Umeda, Isao ^{[1
]}

Shimma, Nobuo ^{[1
]}

机构：

[1] Chugai Pharmaceut Co Ltd, Kamakura Res Labs, Kanagawa 2478530, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2009年 / 19卷 / 07期

关键词：

Anticancer agent; Camptothecin analog; Topoisomerase I inhibitor; BCRP; TOPOISOMERASE-I; CANCER; VITRO;

D O I：

10.1016/j.bmcl.2009.02.031

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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.

引用

页码：2018 / 2021

页数：4

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