Evidence map›Paper›PMID 41635994›Full record

ArticleJournal of medicinal chemistry2026

Enhancement of Potency and Selectivity of 2-Aminoquinoline-Based Human Neuronal Nitric Oxide Synthase Inhibitors.

Anas Ansari, Koon Mook Kang, Huiying Li, Christine D Hardy, Athri D Rathnayake, Amardeep Awasthi, Thomas L Poulos, Richard B Silverman

Abstract read
In one paragraph

Article in Journal of medicinal chemistry, 2026. 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. Dynamic tail amine interactions drive isoform selectivity for potent human neuronal nitric oxide synthase inhibitors.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2026
    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

8 authors.

Anas AnsariDepartment of Chemistry, Department of Molecular Biosciences, Chemistry of Life Processes Institute, Northwestern University, 2145 Sheridan Road, Evanston, Illinois 60208-3113, United States.ORCID 0000-0001-9069-8470
Koon Mook KangDepartment of Chemistry, Department of Molecular Biosciences, Chemistry of Life Processes Institute, Northwestern University, 2145 Sheridan Road, Evanston, Illinois 60208-3113, United States.ORCID 0000-0001-9336-840X
Huiying LiDepartments of Molecular Biology and Biochemistry, Pharmaceutical Sciences, and Chemistry, University of California, Irvine, California 92697-3900, United States.
Christine D HardyDepartments of Molecular Biology and Biochemistry, Pharmaceutical Sciences, and Chemistry, University of California, Irvine, California 92697-3900, United States.ORCID 0000-0002-0780-025X
Athri D RathnayakeORCID 0000-0003-2588-7624
Amardeep AwasthiDepartment of Chemistry, Department of Molecular Biosciences, Chemistry of Life Processes Institute, Northwestern University, 2145 Sheridan Road, Evanston, Illinois 60208-3113, United States.ORCID 0000-0003-3237-9281
Thomas L PoulosDepartments of Molecular Biology and Biochemistry, Pharmaceutical Sciences, and Chemistry, University of California, Irvine, California 92697-3900, United States.ORCID 0000-0002-5648-3510
Richard B SilvermanDepartment of Chemistry, Department of Molecular Biosciences, Chemistry of Life Processes Institute, Northwestern University, 2145 Sheridan Road, Evanston, Illinois 60208-3113, United States.ORCID 0000-0001-9034-1084

Funding

STRUCTURAL STUDIES ON NITRIC OXIDE SYNTHASER01GM057353 · NIGMS · UNIVERSITY OF CALIFORNIA-IRVINE · PI POULOS, THOMAS L · 1998 to 2018
$6.8M
Metalloenzyme structure, function, and as targets for neurodegeneration and bacterial pathogenesisR35GM131920 · NIGMS · UNIVERSITY OF CALIFORNIA-IRVINE · PI POULOS, THOMAS L · 2019 to 2023
$2.9M
Selective inhibition of nitric oxide synthase for multiple indicationsR35GM131788 · NIGMS · NORTHWESTERN UNIVERSITY · PI SILVERMAN, RICHARD B · 2019 to 2023
$2.3M
NIGMS NIH HHS R01 GM057353NIGMS NIH HHS R35 GM131788NIGMS NIH HHS R35 GM131920
6 · The paper itself

Abstract

Neuronal nitric oxide synthase (nNOS) is a key enzyme in neurodegenerative diseases and melanoma, making it an important therapeutic target. We previously reported 2-aminoquinoline-based nNOS inhibitors with promising activity but limited by suboptimal potency, isoform selectivity, and off-target effects. To address these issues, we designed and synthesized a new series of 7-aryl-6-fluoro-4-methyl-2-aminoquinoline derivatives. Compound

Indexed as

AminoquinolinesEnzyme InhibitorsNitric Oxide Synthase Type IAnimalsBlood-Brain BarrierHumansMiceMolecular Dynamics SimulationStructure-Activity RelationshipAminoquinolinesEnzyme InhibitorsNitric Oxide Synthase Type INOS1 protein, human

Identifiers

PMID41635994
PMCPMC12926790

What OpenQuestion holds

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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.