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.
July 14, 2016: ACS Medicinal Chemistry Letters