Bioorganic & Medicinal Chemistry Letters 2012-03-01

Synthesis and biological evaluation of novel amprenavir-based P1-substituted bi-aryl derivatives as ultra-potent HIV-1 protease inhibitors.

Jianwei Yan, Ning Huang, Shukun Li, Liu-Meng Yang, Weiqiang Xing, Yong-Tang Zheng, Youhong Hu

Index: Bioorg. Med. Chem. Lett. 5th ed., 22 , 1976-1979, (2012)

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Abstract

A series of P1-substituted biaryl amprenavir derivatives was designed and synthesized. These compounds were evaluated for enzyme inhibition and antiviral activity in vitro. Several compounds showed highly efficient antiviral activity with EC(50) values down to 0.10nM, which are more potent than marketed HIV-1 protease inhibitors. Docking study indicated that 12c has similar binding mode to amprenavir with full occupancy in P1.Copyright © 2012 Elsevier Ltd. All rights reserved.