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

Journal Article · · ACS Medicinal Chemistry Letters
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  1. Merck Research Lab., West Point, PA (United States)
  2. Merck Frosst Centre for Therapeutic Research, Quebec (Canada)
  3. Albany Molecular Research Singapore Research Center (Singapore)
  4. Albany Molecular Research Singapore Research Center, 61 Science Park Road #05-01, The Galen Singapore Science Park II, Singapore 117525
+ Show Author Affiliations
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.
Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (US)
Sponsoring Organization:
USDOE
OSTI ID:
1404956
Journal Information:
ACS Medicinal Chemistry Letters, Journal Name: ACS Medicinal Chemistry Letters Journal Issue: 7 Vol. 7; ISSN 1948-5875
Publisher:
American Chemical Society (ACS)Copyright Statement
Country of Publication:
United States
Language:
ENGLISH

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Cited By (4)

An in silico pharmacological approach toward the discovery of potent inhibitors to combat drug resistance HIV‐1 protease variants journal December 2018
Two stereocentered HKR of anti -β,β′-diphenylpropanoxirane and anti -3-phenylethyloxiranes catalysed by Co( iii )(salen)-OAc complex: enantioselective synthesis of (+)-sertraline and (+)-naproxen journal January 2018
Comparative study of the nucleophilic attack step in the proteases catalytic activity: A theoretical study journal December 2019
BindingDB Entry 50047800: Discovery of MK-8718, an HIV Protease Inhibitor Containing a Novel Morpholine Aspartate Binding Group. dataset January 2017

Figures / Tables (11)

Figure 1(p. 1)figure Figure 1
Figure 2(p. 2)figure Figure 2
Scheme 1(p. 2)figure Scheme 1
Scheme 3(p. 2)figure Scheme 3
Scheme 2(p. 3)figure Scheme 2
Scheme 4(p. 3)figure Scheme 4
Table 1(p. 3)table Table 1
Scheme 5(p. 4)figure Scheme 5
Scheme 6(p. 4)figure Scheme 6
Table 2(p. 4)table Table 2
Scheme 7(p. 5)figure Scheme 7

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Related Subjects

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
60 APPLIED LIFE SCIENCES
Inhibitors
Peptides and proteins
Rodent models
Substituents
Viruses