Evidence map›Paper›PMID 40252563›Full record

ArticleBioorganic & medicinal chemistry2025

Truncated pyridinylbenzylamines: Potent, selective, and highly membrane permeable inhibitors of human neuronal nitric oxide synthase.

Dhananjayan Vasu, Ha T Do, Huiying Li, Christine D Hardy, Thomas L Poulos, Richard B Silverman

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Bioorganic & medicinal chemistry, 2025. 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. Review
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

6 authors.

Dhananjayan VasuDepartment of Chemistry, Department of Molecular Biosciences, Chemistry of Life Processes Institute, Center for Developmental Therapeutics, Northwestern University, 2145 Sheridan Road, Evanston, IL 60208-3113, United States.
Ha T DoDepartment of Chemistry, Department of Molecular Biosciences, Chemistry of Life Processes Institute, Center for Developmental Therapeutics, Northwestern University, 2145 Sheridan Road, Evanston, IL 60208-3113, United States.
Huiying LiDepartments of Molecular Biology and Biochemistry, Pharmaceutical Sciences, and Chemistry, University of California, Irvine, CA 92697-3900, United States.
Christine D HardyDepartments of Molecular Biology and Biochemistry, Pharmaceutical Sciences, and Chemistry, University of California, Irvine, CA 92697-3900, United States.
Thomas L PoulosDepartments of Molecular Biology and Biochemistry, Pharmaceutical Sciences, and Chemistry, University of California, Irvine, CA 92697-3900, United States. Electronic address: poulos@uci.edu.
Richard B SilvermanDepartment of Chemistry, Department of Molecular Biosciences, Chemistry of Life Processes Institute, Center for Developmental Therapeutics, Northwestern University, 2145 Sheridan Road, Evanston, IL 60208-3113, United States; Department of Pharmacology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, United States. Electronic address: Agman@chem.northwestern.edu.

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 promising target for addressing various neurological disorders and melanoma. Our discovery of a series of truncated pyridinylbenzylamines has yielded potent, selective, and membrane permeable inhibitors of human neuronal nitric oxide synthase. By implementing an efficient synthetic procedure using the Suzuki-Miyaura cross-coupling reaction, we were able to rapidly identify a potent inhibitor. This new inhibitor (18, 6-(2,3-difluoro-5-((methylamino)methyl)phenyl)-4-methylpyridin-2-amine dihydrochloride) exhibits excellent potency, with K

Indexed as

BenzylaminesEnzyme InhibitorsNitric Oxide Synthase Type IPyridinesAnimalsCell Membrane PermeabilityDose-Response Relationship, DrugHumansMolecular StructureRatsStructure-Activity RelationshipBenzylaminesEnzyme InhibitorsNitric Oxide Synthase Type IPyridinesAlzheimer’s DiseaseBlood–Brain BarrierCentral Nervous SystemMelanomaNeurodegenerationNitric OxideNitric Oxide SynthaseParallel Artificial Membrane Permeability Assay (PAMPA)PyridinylbenzylamineRotatable BondsTruncation

Identifiers

PMID40252563
PMCPMC12404148

What Socratic 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 Socratic graph.