Novel seco cyclopropa[c]pyrrolo [3,2-e]indole bisalkylators bearing a 3,3′-arylenebisacryloyl group as a linker

被引：38

作者：

Fukuda, Y ^{[1
]}

Seto, S

Furuta, H

Ebisu, H

Oomori, Y

Terashima, S

机构：

[1] Kyorin Pharmaceut Co Ltd, Cent Res Labs, Nogi, Tochigi 3290114, Japan

[2] Sagami Chem Res Ctr, Sagamihara, Kanagawa 2290012, Japan

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2001年 / 44卷 / 09期

关键词：

D O I：

10.1021/jm000107x

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

We synthesized the novel seco cyclopropa[c]pyrrolo[3,2-e]indole (CPI) bisalkylators and evaluated their antitumor activity. Among these derivatives, 11a (AT-760), in which the two seco 3-methoxycarbonyl-2-trifluoromethyl CPI (MCTFCPI) moieties are connected with a 3,3 '-(1,4-phenylene)bisacryloyl group, was found to exhibit more potent cytotoxicity and antitumor activity against HeLaS3 human uterine cervix carcinoma cells and Colon 26 adenocarcinoma cells, respectively, than 8 (bizelesin, U-77,779). It also appeared that compound 11a exhibits improved in vivo efficacy in the human colon CX-1 model when compared to either compound 8 or mitomycin C (MMC). Efficacious doses for 11a were found to be 2-fold lower than those for 8.

引用

页码：1396 / 1406

页数：11

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