Evidence map›Paper›PMID 39848476›Full record

ArticleBioorganic & medicinal chemistry letters2025

Potent HIV‑1 protease inhibitors containing oxabicyclo octanol-derived P2-ligands: Design, synthesis, and X‑ray structural studies of inhibitor-HIV-1 protease complexes.

Arun K Ghosh, Monika Yadav, Ashish Sharma, Megan Johnson, Ajay K Ghosh, Rangu Prasad, Masayuki Amano, Oksana Gerlits, Andrey Kovalevsky, Hiroaki Mitsuya

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In one paragraph

Article in Bioorganic & medicinal chemistry letters, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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, Purdue University, West Lafayette, IN 47907, USA; Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN 47907, USA. Electronic address: akghosh@purdue.edu.
Monika YadavDepartment of Chemistry, Purdue University, West Lafayette, IN 47907, USA.
Ashish SharmaDepartment of Chemistry, Purdue University, West Lafayette, IN 47907, USA.
Megan JohnsonDepartment of Chemistry, Purdue University, West Lafayette, IN 47907, USA.
Ajay K GhoshDepartment of Chemistry, Purdue University, West Lafayette, IN 47907, USA.
Rangu PrasadDepartment of Chemistry, Purdue University, West Lafayette, IN 47907, USA.
Masayuki AmanoDepartment of Infectious Diseases, Kumamoto University School of Medicine, Kumamoto 860-8556, Japan.
Oksana GerlitsDepartment of Natural Sciences, Tennessee Wesleyan University, Athens, TN 37303, USA.
Andrey KovalevskyNeutron Scattering Division, Oak Ridge National Laboratory, 1 Bethel Valley Road, Oak Ridge, TN 37831, USA.
Hiroaki MitsuyaDepartment of Infectious Diseases, Kumamoto University School of Medicine, Kumamoto 860-8556, Japan; Department of Refractory Infectious Diseases, National Center for Global Health and Medicine Research Institute, Tokyo 162-8655, Japan; Experimental Retrovirology Section, HIV and AIDS Malignancy Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

Funding

Design & Synthesis of Nonpeptide Protease InhibitorsR01AI150466 · NIAID · PURDUE UNIVERSITY · PI ARUN K GHOSH · 2023 to 2026
$2.4M
Design & Synthesis of Nonpeptide Protease InhibitorsR37AI150466 · NIAID · PURDUE UNIVERSITY · PI GHOSH, ARUN K · 2019 to 2020
$969k
NIAID NIH HHS R01 AI150466NIAID NIH HHS R37 AI150466
6 · The paper itself

Abstract

We describe here the design, synthesis, and X-ray structural studies of a new class of HIV-1 protease inhibitors containing 8-oxabicyclo[3.2.1]octanol-derived P2 ligands. We investigated the functional effect of these stereochemically defined fused-poly cyclic ligands on enzyme inhibition and antiviral activity in MT-2 cells. The tricyclic core of 8-oxabicyclo[3.2.1]octan-6-ol is designed to interact with the residues in the S2 subsite of HIV-1 protease. The syntheses of the ligands were carried out using the [5+2]-cycloaddition as the key step. Several inhibitors exhibited potent enzyme inhibitory activity. High resolution room-temperature X-ray structures of inhibitor-bound HIV-1 protease were determined. These structures provided important molecular insights for further design and optimization of inhibitor potency.

Indexed as

Drug DesignHIV ProteaseHIV Protease InhibitorsCrystallography, X-RayDose-Response Relationship, DrugHeterocyclic Compounds, 3-RingHIV-1HumansLigandsModels, MolecularMolecular StructureOctanolsStructure-Activity RelationshipHeterocyclic Compounds, 3-RingHIV ProteaseHIV Protease InhibitorsLigandsOctanolsp16 protease, Human immunodeficiency virus 1Cyclic ligandsCycloadditionHIV-1 proteaseInhibitorX-ray structure

Identifiers

PMID39848476
PMCPMC11956850

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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.