Design, Synthesis, and X-ray Crystallographic Analysis of a Novel Class of HIV-1 Protease Inhibitors

作者：Ganguly Ashit K^*; Alluri Sesha S; Caroccia Danielle; Biswas Dipshikha; Wang Chih Hung; Kang Eunhee; Zhang Yong; McPhail Andrew T; Carroll Steven S; Burlein Christine; Munshi Vandna; Orth Peter; Strickland Corey

来源：Journal of Medicinal Chemistry, 2011, 54(20): 7176-7183.

DOI：10.1021/jm200778q

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 28-30, 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'R,3'S) for optimal potency. X-ray crystallographic analysis has been used to determine the binding mode of the inhibitors to the HIV-1 protease.

• 出版日期2011-10-27