Evidence map›Paper›PMID 30340140›Full record

ArticleEuropean journal of medicinal chemistry2018

Design, synthesis, and X-ray studies of potent HIV-1 protease inhibitors incorporating aminothiochromane and aminotetrahydronaphthalene carboxamide derivatives as the P2 ligands.

Arun K Ghosh, Ravindra D Jadhav, Hannah Simpson, Satish Kovela, Heather Osswald, Johnson Agniswamy, Yuan-Fang Wang, Shin-Ichiro Hattori, Irene T Weber, Hiroaki Mitsuya

Abstract read
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Article in European journal of medicinal chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Article
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, United States. Electronic address: akghosh@purdue.edu.
Ravindra D JadhavDepartment of Chemistry and Department of Medicinal Chemistry, Purdue University, West Lafayette, IN, 47907, United States.
Hannah SimpsonDepartment of Chemistry and Department of Medicinal Chemistry, Purdue University, West Lafayette, IN, 47907, United States.
Satish KovelaDepartment of Chemistry and Department of Medicinal Chemistry, Purdue University, West Lafayette, IN, 47907, United States.
Heather OsswaldDepartment of Chemistry and Department of Medicinal Chemistry, Purdue University, West Lafayette, IN, 47907, United States.
Johnson AgniswamyDepartment of Biology, Molecular Basis of Disease, Georgia State University, Atlanta, GA, 30303, United States.
Yuan-Fang WangDepartment of Biology, Molecular Basis of Disease, Georgia State University, Atlanta, GA, 30303, United States.
Shin-Ichiro HattoriDepartment of Refractory Viral Infections, National Center for Global Health & Medicine Research Institute, Tokyo, 162-8655, Japan.
Irene T WeberDepartment of Biology, Molecular Basis of Disease, Georgia State University, Atlanta, GA, 30303, United States.
Hiroaki MitsuyaDepartment of Refractory Viral Infections, National Center for Global Health & Medicine Research Institute, Tokyo, 162-8655, Japan; Departments of Hematology and Infectious Diseases, Kumamoto University Graduate School of Medical and Pharmaceutical Sciences, Kumamoto, 860-8556, Japan; Experimental Retrovirology Section, HIV and AIDS Malignancy Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, United States.

Funding

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
Structural Analysis of Antiviral Activity of Novel Agents against HIVZIABC011880 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI MITSUYA, HIROAKI · 2019 to 2019
$250k
NIGMS NIH HHS R01 GM053386NIGMS NIH HHS R01 GM062920NIGMS NIH HHS R37 GM053386NIGMS NIH HHS U01 GM062920
6 · The paper itself

Abstract

We describe the design, synthesis, and biological evaluation of a series of novel HIV-1 protease inhibitors with carboxamide derivatives as the P2 ligands. We have specifically designed aminothiochromane and aminotetrahydronaphthalene-based carboxamide ligands to promote hydrogen bonding and van der Waals interactions in the active site of HIV-1 protease. Inhibitors 4e and 4j have shown potent enzyme inhibitory and antiviral activity. High resolution X-ray crystal structures of 4d- and 4k-bound HIV-1 protease revealed molecular insights into the ligand-binding site interactions.

Indexed as

Drug DesignAntiviral AgentsChromansCrystallography, X-RayDose-Response Relationship, DrugHIVHIV ProteaseHIV Protease InhibitorsLigandsModels, MolecularMolecular StructureNaphthalenesStructure-Activity RelationshipAntiviral AgentsChromansHIV ProteaseHIV Protease InhibitorsLigandsNaphthalenesp16 protease, Human immunodeficiency virus 1Design and synthesisDrug resistanceHIV-1 protease inhibitorsP2 ligandX-ray crystal structure

Identifiers

PMID30340140
PMCPMC6237192

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Registered trials

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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.