Novel, potent, and orally bioavailable phosphinic acid inhibitors of the hepatitis C virus NS3 protease

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• 作者：Michael O. Clarke ; ^a ; ^{Michael.Clarke@gilead.com"" rel=""nofollow} ; Xiaowu Chen^a ; Aesop Cho^a ; William E. Delaney IV^a ; Edward Doerffler^a ; Maria Fardis^§ ; ; ^a ; Mingzhe Ji^a ; Michael Mertzman^† ; ; ^a ; Rowchanak Pakdaman^a ; Hyun-Jun Pyun^a ; Tanisha Rowe^‡ ; ; ^a ; Cheng Y. Yang^a ; X. Christopher Sheng^a ; Choung U. Kim^a
• 关键词：HCV ; NS3 protease ; Phosphinic acid ; Carboxylate isostere
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2011
• 出版时间：15 June 2011
• 年：2011
• 卷：21
• 期：12
• 页码：3568-3572
• 全文大小：542 K

文摘

A potent and novel class of product-like inhibitors of the HCV NS3 protease was discovered by employing a phosphinic acid as a carboxylate isostere. The replicon activity and pharmacokinetic profile of this series of compounds was optimized by exploring the substitution of the phosphinic acid, as well as conformationally constraining these compounds through macrocyclization. The syntheses and preliminary biological evaluation of these phosphinic acids is described.