Design, synthesis, and biological properties of highly potent epothilone B analogues

被引：61

作者：

Nicolaou, KC

Sasmal, PK

Rassias, G

Reddy, MV

Altmann, KH

Wartmann, M

O'Brate, A

Giannakakou, P

机构：

[1] Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA

[2] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA

[3] Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA

[4] Novartis Pharma AG, Corp Res, CH-4002 Basel, Switzerland

[5] Novartis Pharma AG, Oncol Business Unit, CH-4002 Basel, Switzerland

[6] Emory Univ, Sch Med, Winship Canc Inst, Atlanta, GA 30322 USA

来源：

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2003年 / 42卷 / 30期

关键词：

antitumor agents; epothilones; structure-activity relationships; sulfur; total synthesis;

D O I：

10.1002/anie.200351819

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

A number of rationally designed epoxide and cyclopropane epothilone B (1) analogues with substituted side chains were prepared and their biological activities were evaluated against a series of human cancer cell lines. The cyclopropane analogue 2 with a methylsulfanylthiazole ring stands out as the most potent compound and is sixfold more active than 1. The methylsulfanyl group enhances the potency of these compounds.

引用

收藏

页码：3515 / 3520

页数：6

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