New water-soluble duocarmycin derivatives:: Synthesis and antitumor activity of A-ring pyrrole compounds bearing β-heteroarylacryloyl groups

被引：31

作者：

Amishiro, N ^{[1
]}

Nagamura, S ^{[1
]}

Kobayashi, E ^{[1
]}

Gomi, K ^{[1
]}

Saito, H ^{[1
]}

机构：

[1] Kyowa Hakko Kogyo Co Ltd, Pharmaceut Res Inst, Shizuoka 4110943, Japan

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1999年 / 42卷 / 04期

关键词：

D O I：

10.1021/jm980559y

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of A-ring pyrrole compounds of duocarmycin bearing 4'-methoxy-beta-heteroarylacryloyl groups were synthesized and evaluated for in vitro anticellular activity against HeLa S-3 cells and in vivo antitumor activity against murine sarcoma 180 in mice. Most of the Li 4'-methoxy-beta-heteroarylacrylates displayed in vitro anticellular activity equivalent to that of 4'-methoxycinnamates, Among the 8-O-[(N-methylpiperazinyl)carbonyl] derivatives of 4'-methoxy-beta-heteroarylacrylates, compound 15b having a (4-methoxy-3,5-pyrimidinyl)acryloyl as segment-B (Seg-B) showed remarkably potent in vivo antitumor activity and low peripheral blood toxicity compared with the A-ring pyrrole derivatives having the trimethoxyindole skeleton in Seg-B, which were equal to 8-O-[(N-methylpiperazinyl)carbonyl] derivatives of 4'-methoxycinnamates. Moreover, these 8-O-[(N-methylpiperazinyl)carbonyl] derivatives of 4'-methoxy-beta-heteroarylacrylates had high aqueous solubility.

引用

页码：669 / 676

页数：8

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