2-Oxo-tetrahydro-1,8-naphthyridines as selective inhibitors of malarial protein farnesyltransferase and as anti-malarials

被引：64

作者：

Olepu, Srinivas ^{[1
]}

Suryadevara, Praveen Kumar ^{[1
]}

Rivas, Kasey ^{[2
]}

Yokoyama, Kohei ^{[1
]}

Verlinde, Christophe L. M. J. ^{[3
]}

Chakrabarti, Debopam ^{[4
]}

Van Voorhis, Wesley C. ^{[2
]}

Gelb, Michael H. ^{[1
,3
]}

机构：

[1] Univ Washington, Dept Chem, Seattle, WA 98195 USA

[2] Univ Washington, Dept Med, Seattle, WA 98195 USA

[3] Univ Washington, Dept Biochem, Seattle, WA 98195 USA

[4] Univ Cent Florida, Dept Mol Biol & Microbiol, Orlando, FL 32826 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2008年 / 18卷 / 02期

关键词：

malaria; P; falciparum; anti-malarials; protein farnesyl-transferase; drug discovery; rational drug design;

D O I：

10.1016/j.bmcl.2007.11.104

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A new class of 2-oxo-tetrahydro-1,8-naphthyridine-based protein farnesyltransferase inhibitors were synthesized and found to inhibit protein farnesyltransferase from the malaria parasite with potencies in the low nanomolar range. The compounds were much less potent on mammalian protein prenyltransferases. Two of the compounds block the growth of malaria in culture with potencies in the sub-micromolar range. Some of the compounds were found to be much more metabolically stable than previously described tetrahydroquinoline-based protein farnesyltransferase inhibitors. (c) 2007 Elsevier Ltd. All rights reserved.

引用

页码：494 / 497

页数：4

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