1. Academic Validation
  2. Discovery of MK-8718, an HIV Protease Inhibitor Containing a Novel Morpholine Aspartate Binding Group

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

  • ACS Med Chem Lett. 2016 May 9;7(7):702-7. doi: 10.1021/acsmedchemlett.6b00135.
Christopher J Bungard 1 Peter D Williams 1 Jeanine E Ballard 1 David J Bennett 1 Christian Beaulieu 2 Carolyn Bahnck-Teets 1 Steve S Carroll 1 Ronald K Chang 1 David C Dubost 1 John F Fay 1 Tracy L Diamond 1 Thomas J Greshock 1 Li Hao 3 M Katharine Holloway 1 Peter J Felock 1 Jennifer J Gesell 1 Hua-Poo Su 1 Jesse J Manikowski 1 Daniel J McKay 2 Mike Miller 1 Xu Min 1 Carmela Molinaro 1 Oscar M Moradei 2 Philippe G Nantermet 1 Christian Nadeau 2 Rosa I Sanchez 1 Tummanapalli Satyanarayana 3 William D Shipe 1 Sanjay K Singh 3 Vouy Linh Truong 2 Sivalenka Vijayasaradhi 3 Catherine M Wiscount 1 Joseph P Vacca 2 Sheldon N Crane 2 John A McCauley 1
Affiliations

Affiliations

  • 1 Merck Research Laboratories , 770 Sumneytown Pike, PO Box 4, West Point, Pennsylvania 19486, United States.
  • 2 Merck Frosst Centre for Therapeutic Research , 16711 TransCanada Highway, Kirkland, Quebec H9H 3L1, Canada.
  • 3 Albany Molecular Research Singapore Research Center , 61 Science Park Road #05-01, The Galen Singapore Science Park II, Singapore 117525.
Abstract

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.

Keywords

HIV; MK-8718; inhibitor; protease.

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