Discovery of MK-8718, an HIV Protease Inhibitor Containing a Novel Morpholine Aspartate Binding Group

详细信息    查看全文

• 作者：Christopher J. Bungard ; Peter D. Williams ; Jeanine E. Ballard ; David J. Bennett ; Christian Beaulieu ; Carolyn Bahnck-Teets ; Steve S. Carroll ; Ronald K. Chang ; David C. Dubost ; John F. Fay ; Tracy L. Diamond ; Thomas J. Greshock ; Li Hao ; M. Katharine Holloway ; Peter J. Felock ; Jennifer J. Gesell ; Hua-Poo Su ; Jesse J. Manikowski ; Daniel J. McKay ; Mike Miller ; Xu Min ; Carmela Molinaro ; Oscar M. Moradei ; Philippe G. Nantermet ; Christian Nadeau ; Rosa I. Sanchez ; Tummanapalli Satyanarayana ; William D. Shipe ; Sanjay K. Singh ; Vouy Linh Truong ; Sivalenka Vijayasaradhi ; Catherine M. Wiscount ; Joseph P. Vacca ; Sheldon N. Crane ; John A. McCauley
• 刊名：ACS Medicinal Chemistry Letters
• 出版年：2016
• 出版时间：July 14, 2016
• 年：2016
• 卷：7
• 期：7
• 页码：702-707
• 全文大小：400K
• 年卷期：0
• ISSN：1948-5875

文摘

A novel HIV protease inhibitor was designed using a morpholine core as the aspartate binding group. Analysis of the crystal structure of the initial lead bound to HIV protease enabled optimization of enzyme potency and antiviral activity. This afforded a series of potent orally bioavailable inhibitors of which MK-8718 was identified as a compound with a favorable overall profile.