Microwave-accelerated synthesis of p1′-extended HIV-1 protease inhibitors encompassing a tertiary alcohol in the transition-state mimicking scaffold

被引：43

作者：

Ekegren, JK

Ginman, N

Johansson, Å

Wallberg, H

Larhed, M

Samuelsson, B

Unge, T

Hallberg, A

机构：

[1] Uppsala Univ, Dept Med Chem, BMC, SE-75123 Uppsala, Sweden

[2] Uppsala Univ, Dept Cell & Mol Biol, BMC, SE-75124 Uppsala, Sweden

[3] Medivir AB, SE-14144 Huddinge, Sweden

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2006年 / 49卷 / 05期

关键词：

D O I：

10.1021/jm051239z

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Two series of P1'-extended HIV-1 protease inhibitors comprising a tertiary alcohol in the transition-state mimic exhibiting K-i values ranging from 2.1 to 93 nM have been synthesized. Microwave-accelerated palladium-catalyzed cross-couplings were utilized to rapidly optimize the P1' side chain. High cellular antiviral potencies were encountered when the P1' benzyl group was elongated with a 3- or 4-pyridyl substituent (EC50 = 0.18-0.22 mu M). X-ray crystallographic data were obtained for three inhibitors cocrystallized with the enzyme.

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页码：1828 / 1832

页数：5

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