Design and synthesis of pyridone inhibitors of non-nucleoside reverse transcriptase

详细信息    查看全文

• 作者：Robert  ; Gomez^a ;   ; ^{Robert_gomez@merck.com} ; Samson  ; Jolly^a ; Theresa  ; Williams^a ; Thomas  ; Tucker^a ; Robert  ; Tynebor^a ; Joe  ; Vacca^a ; Georgia  ; McGaughey^b ; Ming-Tain  ; Lai^c ; Peter  ; Felock^d ; Vandna  ; Munshi^c ; Daniel  ; DeStefano^d ; Sinoeun  ; Touch^c ; Mike  ; Miller^d ; Youwei  ; Yan^e ; Rosa  ; Sanchez^f ; Yuexia  ; Liang^f ; Brenda  ; Paton^f ; Bang-Lin  ; Wan^f ; Neville  ; Anthony^g
• 关键词：Non-nucleoside reverse transcriptase inhibitor ; Pyridone ; Pyridinone ; HIV
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2011
• 出版时间：15 December 2011
• 年：2011
• 卷：21
• 期：24
• 页码：7344-7350
• 全文大小：1049 K

文摘

Next generation NNRTIs are sought which possess both broad spectrum antiviral activity against key mutant strains and a high genetic barrier to the selection of new mutant viral strains. Pyridones were evaluated as an acyclic conformational constraint to replace the aryl ether core of MK-4965 (1) and the more rigid indazole constraint of MK-6186 (2). The resulting pyridone compounds are potent inhibitors of HIV RT and have antiviral activity in cell culture that is superior to other next generation NNRTI¡¯s.