Synthesis and evaluation of novel a-amino cyclic boronates as inhibitors of HCV NS3 protease
journal contribution
posted on 2023-06-08, 21:48authored byXianfeng Li, Yong-Kang Zhang, Yang Liu, Charles Z Ding, Qun Li, Yasheen Zhou, Jacob J Plattner, Stephen J Baker, Xuelei Qian, Dazhong Fan, Liang Liao, Zhi-Jie Ni, Gemma V White, Jackie E Mordaunt, Linos X Lazarides, Martin J Slater, Richard L Jarvest, Pia Thommes, Malcolm Ellis, Colin M Edge, Julia A Hubbard, Don Somers, Paul Rowland, Pamela Nassau, Bill McDowell, Tadeusz J Skarzynski, Wieslaw M Kazmierski, Richard M Grimes, Lois L. Wright, Gary K Smith, Wuxin Zou, Jon Wright, Lewis E Pennicott
We have designed and synthesized a novel series of alpha-amino cyclic boronates and incorporated them successfully in several acyclic templates at the P1 position. These compounds are inhibitors of the HCV NS3 serine protease, and structural studies show that they inhibit the NS3 protease by trapping the Ser-139 hydroxyl group in the active site. Synthetic methodologies and SARs of this series of compounds are described.