A new class of HIV-1 protease inhibitors containing a tertiary alcohol in the transition-state mimicking scaffold

被引：40

作者：

Ekegren, JK

Unge, T

Safa, MZ

Wallberg, H

Samuelsson, B

Hallberg, A

机构：

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

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

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

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2005年 / 48卷 / 25期

关键词：

D O I：

10.1021/jm050790t

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Novel HIV-1 protease inhibitors encompassing a tertiary alcohol as part of the transition-state mimicking unit have been synthesized. Variation of the P-1'-P-3' residues and alteration of the tertiary alcohol absolute stereochemistry afforded 10 inhibitors. High potencies for the compounds with (S)-configuration at the carbon carrying the tertiary hydroxyl group were achieved with K-i values down to 2.4 nM. X-ray crystallographic data for a representative compound in complex with HIV-1 protease are presented.

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页码：8098 / 8102

页数：5

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