Cyclic sulfamide HIV-1 protease inhibitors, with sidechains spanning from P2/P2′ to P1/P1′

被引：41

作者：

Ax, A

Schaal, W

Vrang, L

Samuelsson, B

Hallberg, A

Karlén, A

机构：

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

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

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2005年 / 13卷 / 03期

关键词：

AIDS; HIV-1 protease inhibitors; cyclic sulfamide; molecular modeling;

D O I：

10.1016/j.bmc.2004.10.042

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Previous studies of HIV protease inhibitors have shown that it is possible to elongate the P1/P1' sidechains to reach the S3/S3' binding sites. By analogy, We expected that it would be possible to design inhibitors reaching between the S1/S1' and S2/S2' binding sites. Molecular modeling suggested that this could be achieved with appropriate ortho-substitution of the P2/P2' benzyl groups in our cyclic sulfamide inhibitors. Four different spacer groups were investigated. The compounds were smoothly prepared 44 from tartaric acid in five steps and exhibit low to moderate activity, the most potent inhibitor possessing a K-i value of 0.53 muM. (C) 2004 Elsevier Ltd. All rights reserved.

引用

页码：755 / 764

页数：10

共 29 条

[1] Unexpected binding mode of a cyclic sulfamide HIV-1 protease inhibitor [J].