Design, Synthesis, and SAR of Naphthyl-Substituted Diarylpyrimidines as Non-Nucleoside Inhibitors of HIV-1 Reverse Transcriptase

✍ Scribed by Yong-Hong Liang; Xiao-Qing Feng; Zhao-Sen Zeng; Fen-Er Chen; Jan Balzarini; Christophe Pannecouque; Erik De Clercq

• Publisher: John Wiley and Sons
• Year: 2009
• Tongue: English
• Weight: 314 KB
• Volume: 4
• Category: Article
• ISSN: 1860-7179
• DOI: 10.1002/cmdc.200900212

✦ Synopsis

Abstract

A series of 38 2‐naphthyl‐substituted diarylpyrimidine (DAPY) analogues, characterized by various substitution patterns on the pyrimidine and naphthalene rings, was synthesized in a straightforward fashion by means of parallel synthesis and evaluated as inhibitors of the HIV‐1 wild‐type and double mutant (K103N+Y181C) strains. Most of the compounds displayed strong activity against wild‐type HIV‐1. The most active compound, with a cyano group at position C6 on the naphthalene ring, exhibited activity against wild‐type HIV‐1 with an EC~50~ value of 0.002 μM and against the double mutant strain with an EC~50~ value of 0.24 μM; the selectivity index (SI) against wild‐type is >180 000, the highest SI value among DAPY analogues. The structure–activity relationship (SAR) of the newly synthesized DAPYs is presented herein.