Structure-activity relationships of 4-hydroxy-4-biaryl-proline acylsulfonamide tripeptides: A series of potent NS3 protease inhibitors for the treatment of hepatitis C virus

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• 作者：Alan Xiangdong Wang^a ; ^{alan.wang@bms.com} ; Jie Chen^a ; Qian Zhao^a ; Li-Qiang Sun^a ; Jacques Friborg^b ; Fei Yu^b ; Dennis Hernandez^b ; Andrew C. Good^c ; Herbert E. Klei^c ; Ramkumar Rajamani^c ; Kathy Mosure^d ; Jay O. Knipe^d ; Danshi Li^d ; Jialong Zhu^d ; Paul C. Levesque^d ; Fiona McPhee^b ; Nicholas A. Meanwell^a ; Paul M. Scola^a ;
• 关键词：HCV NS3/4A serine protease inhibitors ; Tripeptide acylsulfonamides ; C4 aryl ; C4 hydroxy-proline ; Potent and orally bioavailable ; Cardiovascular profiles
• 刊名：Bioorganic & Medicinal Chemistry Letters
• 出版年：2017
• 出版时间：1 February 2017
• 年：2017
• 卷：27
• 期：3
• 页码：590-596
• 全文大小：3260 K
• 卷排序：27

文摘

The design and synthesis of a series of tripeptide acylsulfonamides as potent inhibitors of the HCV NS3/4A serine protease is described. These analogues house a C4 aryl, C4 hydroxy-proline at the S2 position of the tripeptide scaffold. Information relating to structure-activity relationships as well as the pharmacokinetic and cardiovascular profiles of these analogues is provided.