Evidence map›Paper›PMID 29110408›Full record

ArticleChemMedChem2017

Design, Synthesis, Biological Evaluation, and X-ray Studies of HIV-1 Protease Inhibitors with Modified P2' Ligands of Darunavir.

Arun K Ghosh, W Sean Fyvie, Margherita Brindisi, Melinda Steffey, Johnson Agniswamy, Yuan-Fang Wang, Manabu Aoki, Masayuki Amano, Irene T Weber, Hiroaki Mitsuya

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in ChemMedChem, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Arun K GhoshDepartment of Chemistry and Department of Medicinal Chemistry, Purdue University, West Lafayette, IN, 47907, USA.ORCID 0000-0003-2472-1841
W Sean FyvieDepartment of Chemistry and Department of Medicinal Chemistry, Purdue University, West Lafayette, IN, 47907, USA.
Margherita BrindisiDepartment of Chemistry and Department of Medicinal Chemistry, Purdue University, West Lafayette, IN, 47907, USA.
Melinda SteffeyDepartment of Chemistry and Department of Medicinal Chemistry, Purdue University, West Lafayette, IN, 47907, USA.
Johnson AgniswamyDepartments of Biology and Chemistry, Molecular Basis of Disease, Georgia State University, Atlanta, GA, 30303, USA.
Yuan-Fang WangDepartments of Biology and Chemistry, Molecular Basis of Disease, Georgia State University, Atlanta, GA, 30303, USA.
Manabu AokiDepartments of Hematology and Infectious Diseases, Kumamoto University School of Medicine, Kumamoto, 860-8556, Japan.
Masayuki AmanoDepartments of Hematology and Infectious Diseases, Kumamoto University School of Medicine, Kumamoto, 860-8556, Japan.
Irene T WeberDepartments of Biology and Chemistry, Molecular Basis of Disease, Georgia State University, Atlanta, GA, 30303, USA.
Hiroaki MitsuyaDepartments of Hematology and Infectious Diseases, Kumamoto University School of Medicine, Kumamoto, 860-8556, Japan.

Funding

Development of Antiviral Therapy of HIV-1 InfectionZIASC006738 · NCI · DIVISION OF CLINICAL SCIENCES - NCI · PI MITSUYA, HIROAKI · 2009 to 2025
$10.0M
Design & Synthesis of Nonpeptide Protease InhibitorsR37GM053386 · NIGMS · PURDUE UNIVERSITY · PI GHOSH, ARUN K · 2011 to 2018
$3.9M
DESIGN AND SYNTHESIS OF NONPEPTIDE PROTEASE INHIBITORSR01GM053386 · NIGMS · UNIVERSITY OF ILLINOIS AT CHICAGO · PI GHOSH, ARUN K · 1995 to 2010
$3.7M
ACTIVITY OF RESISTANT VARIANTS OF HIV PROTEASER01GM062920 · NIGMS · GEORGIA STATE UNIVERSITY · PI WEBER, IRENE T · 2000 to 2012
$3.3M
Inhibition of Resistant Variants of HIV ProteaseU01GM062920 · NIGMS · GEORGIA STATE UNIVERSITY · PI HARRISON, ROBERT WILSON, WEBER, IRENE T · 2013 to 2018
$2.1M
NIGMS NIH HHS R01 GM053386NIGMS NIH HHS R01 GM062920NIGMS NIH HHS R37 GM053386NIGMS NIH HHS U01 GM062920
6 · The paper itself

Abstract

The structure-based design, synthesis, and biological evaluation of a series of nonpeptidic HIV-1 protease inhibitors with rationally designed P2' ligands are described. The inhibitors are designed to enhance backbone binding interactions, particularly at the S2' subsite. Synthesis of inhibitors was carried out efficiently. The stereochemistry of alcohol functionalities of the P2' ligands was set by asymmetric reduction of the corresponding ketone using (R,R)- or (S,S)-Noyori catalysts. A number of inhibitors displayed very potent enzyme inhibitory and antiviral activity. Inhibitors 3g and 3h showed enzyme K

Indexed as

Drug DesignCrystallography, X-RayDarunavirHIV ProteaseHIV Protease InhibitorsLigandsModels, MolecularMolecular ConformationStructure-Activity RelationshipDarunavirHIV ProteaseHIV Protease InhibitorsLigandsp16 protease, Human immunodeficiency virus 1drug resistanceHIV-1 protease inhibitorsP2′ ligandspharmacokineticsstructure-based design

Identifiers

PMID29110408
PMCPMC5896574

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.