2-oxotetrahydroquinoline-based antimalarials with high potency and metabolic stability

被引：26

作者：

Bulbule, Vivek J. ^{[1
]}

Rivas, Kasey ^{[2
]}

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

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

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2008年 / 51卷 / 03期

关键词：

D O I：

10.1021/jm7013138

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

We report a series of novel inhibitors of protein farnesyltransferase based on the 2-oxotetrahydroquinoline scaffold. We developed an efficient synthesis of these compounds. These compounds show selective inhibtion of the malaria versus human farnesyltransferase and inhibit the growth of the malaria parasite in the low nanomolar range. Some of the compounds are at least an order of magnitude more stable to metabolic degradation than the corresponding tetrahydroquinolines.

引用

页码：384 / 387

页数：4

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