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. eCollection 2016 Jul 14.

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.