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

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posted on 09.05.2016, 00:00 by 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
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.

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