Nucleotide competing reverse transcriptase inhibitors: Discovery of a series of non-basic benzofurano[3,2-d]pyrimidin-2-one derived inhibitors

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• 作者：Clint A. James ; ^{clint.james@boehringer-ingelheim.com} ; Patrick DeRoy ; Martin Duplessis ; Paul J. Edwards ; Teddy Halmos ; Joannie Minville ; Louis Morency^&dagger ; ; Sé ; bastien Morin ; Bruno Simoneau ; ^{bruno.simoneau@boehringer-ingelheim.com} ; Martin Tremblay ; Richard Bethell ; Michael Cordingley ; Jianmin Duan ; Louie Lamorte ; Alex Pelletier ; Daniel Rajotte ; Patrick Salois ; Sonia Tremblay ; Claudio F. Sturino
• 关键词：JFIAVEATUHYZRN-SFHVURJKSA-N
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2013
• 出版时间：1 May, 2013
• 年：2013
• 卷：23
• 期：9
• 页码：2781-2786
• 全文大小：523 K

文摘

A HTS screen led to the identification of a benzofurano[3,2-d]pyrimidin-2-one core structure which upon further optimization resulted in 1 as a potent HIV-1 nucleotide competing reverse transcriptase inhibitor (NcRTI). Investigation of the SAR at N-1 allowed significant improvements in potency and when combined with the incorporation of heterocycles at C-8 resulted in potent analogues not requiring a basic amine to achieve antiviral activity. Additional modifications at N-1 resulted in 33 which demonstrated excellent antiviral potency and improved physicochemical properties.