Literature DB >> 27437081

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

Christopher J Bungard1, Peter D Williams1, Jeanine E Ballard1, David J Bennett1, Christian Beaulieu2, Carolyn Bahnck-Teets1, Steve S Carroll1, Ronald K Chang1, David C Dubost1, John F Fay1, Tracy L Diamond1, Thomas J Greshock1, Li Hao3, M Katharine Holloway1, Peter J Felock1, Jennifer J Gesell1, Hua-Poo Su1, Jesse J Manikowski1, Daniel J McKay2, Mike Miller1, Xu Min1, Carmela Molinaro1, Oscar M Moradei2, Philippe G Nantermet1, Christian Nadeau2, Rosa I Sanchez1, Tummanapalli Satyanarayana3, William D Shipe1, Sanjay K Singh3, Vouy Linh Truong2, Sivalenka Vijayasaradhi3, Catherine M Wiscount1, Joseph P Vacca2, Sheldon N Crane2, John A McCauley1.   

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.

Entities:  

Keywords:  HIV; MK-8718; inhibitor; protease

Year:  2016        PMID： 27437081      PMCID： PMC4948015          DOI： 10.1021/acsmedchemlett.6b00135

Source DB:  PubMed          Journal:  ACS Med Chem Lett        ISSN： 1948-5875            Impact factor:   4.345


  15 in total

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Authors:  Christopher J Bungard; Peter D Williams; Jurgen Schulz; Catherine M Wiscount; M Katharine Holloway; H Marie Loughran; Jesse J Manikowski; Hua-Poo Su; David J Bennett; Lehua Chang; Xin-Jie Chu; Alejandro Crespo; Michael P Dwyer; Kartik Keertikar; Gregori J Morriello; Andrew W Stamford; Sherman T Waddell; Bin Zhong; Bin Hu; Tao Ji; Tracy L Diamond; Carolyn Bahnck-Teets; Steven S Carroll; John F Fay; Xu Min; William Morris; Jeanine E Ballard; Michael D Miller; John A McCauley
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4.  Design, synthesis, and X-ray studies of potent HIV-1 protease inhibitors incorporating aminothiochromane and aminotetrahydronaphthalene carboxamide derivatives as the P2 ligands.

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