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

被引：20

作者：

Bungard, Christopher J. ^{[1
]}

Williams, Peter D. ^{[1
]}

Ballard, Jeanine E. ^{[1
]}

Bennett, David J. ^{[1
]}

Beaulieu, Christian ^{[2
]}

Bahnck-Teets, Carolyn ^{[1
]}

Carroll, Steve S. ^{[1
]}

Chang, Ronald K. ^{[1
]}

Dubost, David C. ^{[1
]}

Fay, John F. ^{[1
]}

Diamond, Tracy L. ^{[1
]}

Greshock, Thomas J. ^{[1
]}

Hao, Li ^{[3
]}

Holloway, M. Katharine ^{[1
]}

Felock, Peter J.

Gesell, Jennifer J. ^{[1
]}

Su, Hua-Poo ^{[1
]}

Manikowski, Jesse J. ^{[1
]}

McKay, Daniel J. ^{[2
]}

Miller, Mike ^{[1
]}

Min, Xu ^{[1
]}

Molinaro, Carmela ^{[1
]}

Moradei, Oscar M. ^{[2
]}

Nantermet, Philippe G. ^{[1
]}

Nadeau, Christian ^{[2
]}

Sanchez, Rosa I. ^{[1
]}

Satyanarayana, Tummanapalli ^{[3
]}

Shipe, William D. ^{[1
]}

Singh, Sanjay K. ^{[3
]}

Vouy Linh Truong ^{[2
]}

Vijayasaradhi, Sivalenka ^{[3
]}

Wiscount, Catherine M. ^{[1
]}

Vacca, Joseph P. ^{[2
]}

Crane, Sheldon N. ^{[2
]}

McCauley, John A. ^{[1
]}

机构：

[1] Merck Res Labs, 770 Sumneytown Pike,POB 4, West Point, PA 19486 USA

[2] Merck Frosst Ctr Therapeut Res, 16711 TransCanada Highway, Kirkland, PQ H9H 3L1, Canada

[3] Albany Mol Res Singapore Res Ctr, 61 Sci Pk Rd 05-01,Galen Singapore Sci Pk 2, Singapore 117525, Singapore

来源：

ACS MEDICINAL CHEMISTRY LETTERS | 2016年 / 7卷 / 07期

关键词：

MK-8718; HIV; protease; inhibitor; ACIDS;

D O I：

10.1021/acsmedchemlett.6b00135

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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.

引用

页码：702 / 707

页数：6

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