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

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.

SUBMITTER: Bungard CJ

PROVIDER: S-EPMC4948015 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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

Bungard Christopher J CJ Williams Peter D PD Ballard Jeanine E JE Bennett David J DJ Beaulieu Christian C Bahnck-Teets Carolyn C Carroll Steve S SS Chang Ronald K RK Dubost David C DC Fay John F JF Diamond Tracy L TL Greshock Thomas J TJ Hao Li L Holloway M Katharine MK Felock Peter J PJ Gesell Jennifer J JJ Su Hua-Poo HP Manikowski Jesse J JJ McKay Daniel J DJ Miller Mike M Min Xu X Molinaro Carmela C Moradei Oscar M OM Nantermet Philippe G PG Nadeau Christian C Sanchez Rosa I RI Satyanarayana Tummanapalli T Shipe William D WD Singh Sanjay K SK Truong Vouy Linh VL Vijayasaradhi Sivalenka S Wiscount Catherine M CM Vacca Joseph P JP Crane Sheldon N SN McCauley John A JA

ACS medicinal chemistry letters 20160509 7

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. ...[more]

PMID: 27437081

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