Discovery of GS-8374, a potent human immunodeficiency virus type 1 protease inhibitor with a superior resistance profile

作者：Gong-Xing He, Zhengyu Yang, Matthew A. Williams, Christian Callebaut, Tomáš Cihlář, Bernard P. Murray, Chris Yang, Michael L. Mitchell, Hongtao Liu, Jianying Wang, Murty N. Arimilli, Eugene Eisenberg, Kirsten M. Stray, Luong Tsai, Marcos Hatada, Xiaowu Chen, James Chen, Yujin Wang, Melody S. Lee, Robert G. Strickley, Quynh Iwata, Xubin Zheng, Choung U. Kim, S. Swaminathan, Manoj C. Desai, William A. Lee, Lianhong Xu · 发表于：MedChemComm · 年份：2011 · DOI：10.1039/c1md00147g · 被引用次数：15 · 研究领域：HIV/AIDS drug development and treatment、HIV Research and Treatment、Pneumocystis jirovecii pneumonia detection and treatment

Introduction of a unique phosphonate moiety at the P1 position of the TMC-126 (3) scaffold provided a series of novel HIV-1 protease inhibitors (PIs) with an improved resistance profile against highly resistant variants. Optimization of the linker and phosphonate moieties lead to the identification of GS-8374 (1). Compound 1 is a potent and orally bioavailable HIV-1 PI with a superior resistance profile. Synthesis and characterization of 1 are reported.