Synthesis and structure-activity relationships of novel 2',2'-difluoro analogues of docetaxel

被引：0

作者：

Uoto, K ^{[1
]}

Ohsuki, S ^{[1
]}

Takenoshita, H ^{[1
]}

Ishiyama, T ^{[1
]}

Iimura, S ^{[1
]}

Hirota, Y ^{[1
]}

Mitsui, I ^{[1
]}

Terasawa, H ^{[1
]}

Soga, T ^{[1
]}

机构：

[1] DAIICHI PHARMACEUT CO LTD, NEW PROD RES LABS 4, EDOGAWA KU, TOKYO 134, JAPAN

来源：

CHEMICAL & PHARMACEUTICAL BULLETIN | 1997年 / 45卷 / 11期

关键词：

docetaxel; paclitaxel; 2'; 2'-difluoro analogue; structure-activity relationship; cytotoxicity; microtubule disassembly-inhibitory activity;

D O I：

暂无

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

To investigate the role of the 2'-hydroxy group at the C-13 side chain of docetaxel in the antitumor activity, we prepared several 2',2'-difluoro derivatives of docetaxel and evaluated their cytotoxicity against mouse leukemia and human tumor cell lines and their microtubule disassembly-inhibitory activity. These analogues were prepared by esterification of protected 10-deacetylbaccatin III (21) with appropriate alpha,alpha-difluorinated carboxylic acids (Charts 1 and 2). Among these 2',2'-difluorodocetaxel derivatives, 2',2'-difluorodocetaxel (23b) was approximately 3-10 times as active as 2'-fluorodocetaxel (29a) in terms of cytotoxicity. In addition, the 3'-(2-furyl) (23h) and 3'-(2-pyrrolyl) (23p) analogues showed activity comparable or superior to that of docetaxel (2).

引用

页码：1793 / 1804

页数：12

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