Design, Synthesis, and X-ray Crystallographic Analysis of a Novel Class of HIV-1 Protease Inhibitors
详细信息 查看全文
- 作者：Ashit K. Ganguly ; Sesha S. Alluri ; Danielle Caroccia ; Dipshikha Biswas ; Chih-Hung Wang ; Eunhee Kang ; Yong Zhang ; Andrew T. McPhail ; Steven S. Carroll ; Christine Burlein ; Vandna Munshi ; Peter Orth ; Corey Strickland
- 刊名：Journal of Medicinal Chemistry
- 出版年：2011
- 出版时间：October 27, 2011
- 年：2011
- 卷：54
- 期：20
- 页码：7176-7183
- 全文大小：942K
- 年卷期：v.54,no.20(October 27, 2011)
- ISSN：1520-4804
文摘
In the present paper, design, synthesis, X-ray crystallographic analysis, and HIV-1 protease inhibitory activities of a novel class of compounds are disclosed. Compounds 28鈥?b>30, 32, 35, and 40 were synthesized and found to be inhibitors of the HIV-1 protease. The crucial step in their synthesis involved an unusual endo radical cyclization process. Absolute stereochemistry of the three asymmetric centers in the above compounds have been established to be (4S,2鈥?i>R,3鈥?i>S) for optimal potency. X-ray crystallographic analysis has been used to determine the binding mode of the inhibitors to the HIV-1 protease.