Discovery of GS-9256: A novel phosphinic acid derived inhibitor of the hepatitis C virus NS3/4A protease with potent clinical activity

详细信息    查看全文

• 作者：X. Christopher Sheng ; ^{csheng@gilead.com} ; Anthony Casarez ; Ruby Cai ; Michael O. Clarke ; Xiaowu Chen ; Aesop Cho ; William E. Delaney IV ; Edward Doerffler ; Mingzhe Ji ; Michael Mertzman^&dagger ; ; Rowchanak Pakdaman ; Hyung-Jung Pyun ; Tanisha Rowe^&Dagger ; ; Qiaoyin Wu ; Jie Xu ; Choung U. Kim
• 关键词：GS-9256 ; HCV ; NS3/4A protease inhibitor ; Phosphinic acid ; Carboxylate isostere
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2012
• 出版时间：1 February, 2012
• 年：2012
• 卷：22
• 期：3
• 页码：1394-1396
• 全文大小：344 K

文摘

A potent and novel class of phosphinic acid derived product-like inhibitors of the HCV NS3/4A protease was discovered previously. Modification of the phosphinic acid and quinoline heterocycle led to GS-9256 with potent cell-based activity and favorable pharmacokinetic parameters. Based on these attributes, GS-9256 was advanced to human clinical trial as a treatment for chronic infection with genotype 1 HCV.