第二代丙型肝炎病毒NS3/4A丝氨酸蛋白酶抑制剂研究进展

摘要

本文综述了近年来基于特拉匹韦(telaprevir)、波西匹韦(boceprevir)和BILN-2061等第一代HCV NS3/4A丝氨酸蛋白酶抑制剂的第二代抑制剂的结构改造.第二代抑制剂可有效提高抑制效力,显著改善药代动力学参数,可在一定程度上克服由第一代抑制剂诱导产生的耐药性.同时探讨了各类抑制剂的构效关系.%The progress of the second generation inhibitors of HCV NS3/4A serine protease, based on the modifications to the first generation ones (telaprevir, boceprevir, BILN-2061), is reviewed. The second generation inhibitors can significantly improve potency, pharmacokinetic profiles, and to some degree reduce the resistance induced by the first generation ones. The structure-activity relationships of these inhibitors are also discussed.