Synthesis and biological evaluation of 2-indolyloxazolines as a new class of tubulin polymerization inhibitors. Discovery of A-289099 as an orally active antitumor agent

被引：114

作者：

Li, Q ^{[1
]}

Woods, KW ^{[1
]}

Claiborne, A ^{[1
]}

Gwaltney, SL ^{[1
]}

Barr, KJ ^{[1
]}

Liu, G ^{[1
]}

Gehrke, L ^{[1
]}

Credo, RB ^{[1
]}

Hui, YH ^{[1
]}

Lee, J ^{[1
]}

Warner, RB ^{[1
]}

Kovar, P ^{[1
]}

Nukkala, MA ^{[1
]}

Zielinski, NA ^{[1
]}

Tahir, SK ^{[1
]}

Fitzgerald, M ^{[1
]}

Kim, KH ^{[1
]}

Marsh, K ^{[1
]}

Frost, D ^{[1
]}

Ng, SC ^{[1
]}

Rosenberg, S ^{[1
]}

Sham, HL ^{[1
]}

机构：

[1] Abbott Labs, Abbott Pk, IL 60064 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2002年 / 12卷 / 03期

关键词：

D O I：

10.1016/S0960-894X(01)00759-4

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of indole containing oxazolines has been discovered as a result of structural modifications of the lead compound A-105972. The compounds exert their anticancer activity through inhibition of tubulin polymerization by binding at the colchicine site. A-289099 was identified as an orally active antimitotic agent active against various cancer cell lines including those that express the MDR phenotype. The anticancer activity, pharmacokinetics, and an efficient and enantioselective synthesis of A-289099 are described. (C) 2002 Elsevier Science Ltd. All rights reserved.

引用

页码：465 / 469

页数：5

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