Discovery of MK-1439, an orally bioavailable non-nucleoside reverse transcriptase inhibitor potent against a wide range of resistant mutant HIV viruses

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• 作者：Bernard C么t茅 ; Jason D. Burch ; Ernest Asante-Appiah ; Chris Bayly ; Leanne B茅dard ; Marc Blouin ; Louis-Charles Campeau ; Elizabeth Cauchon ; Manuel Chan ; Am ; ine Chefson ; Nathalie Coulombe ; W ; a Cromlish ; Smita Debnath ; Denis Desch锚nes ; Kristina Dupont-Gaudet ; Jean-Pierre Falgueyret ; Robert Forget ; S茅bastien Gagn茅 ; Danny Gauvreau ; Melina Girardin ; S茅bastien Guiral ; et al.
• 关键词：Non-nucleoside reverse transcriptase ; HIV ; Triazolinone ; Pyridone ; Inhibitor
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：1 February, 2014
• 年：2014
• 卷：24
• 期：3
• 页码：917-922
• 全文大小：2365 K

文摘

The optimization of a novel series of non-nucleoside reverse transcriptase inhibitors (NNRTI) led to the identification of pyridone 36. In cell cultures, this new NNRTI shows a superior potency profile against a range of wild type and clinically relevant, resistant mutant HIV viruses. The overall favorable preclinical pharmacokinetic profile of 36 led to the prediction of a once daily low dose regimen in human. NNRTI 36, now known as MK-1439, is currently in clinical development for the treatment of HIV infection.