Evidence map›Paper›PMID 35772285›Full record

ArticleBioorganic & medicinal chemistry2022

2-Aminopyridines with a shortened amino sidechain as potent, selective, and highly permeable human neuronal nitric oxide synthase inhibitors.

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

Open access · greenAbstract read
In one paragraph

Article in Bioorganic & medicinal chemistry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.7field-weighted citation impact, top 16% of its field
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

9 citing papers in PubMed, 15 citations in OpenAlex.

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  8. Molecules (Basel, Switzerland) · 2023
    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

5 authors at 2 institutions in 1 country.

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.
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.
University of California, Irvine · USNorthwestern University · US

Funding

Univ.of Calif., Irvine Cancer Center Support GrantP30CA062203 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI Melanie Funes · 1994 to 2026
$57.9M
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
NCI NIH HHS P30 CA062203NIGMS NIH HHS R01 GM057353NIGMS NIH HHS R35 GM131788NIGMS NIH HHS R35 GM131920
6 · The paper itself

Abstract

A series of potent, selective, and highly permeable human neuronal nitric oxide synthase inhibitors (hnNOS) based on the 2-aminopyridine scaffold with a shortened amino sidechain is reported. A rapid and simple protocol was developed to access these inhibitors in excellent yields. Neuronal nitric oxide synthase (nNOS) is a novel therapeutic target for the treatment of various neurological disorders. The major challenges in designing nNOS inhibitors in humans focus on potency, selectivity over other isoforms of nitric oxide synthases (NOSs), and blood-brain barrier permeability. In this context, we discovered a promising inhibitor, 6-(3-(4,4-difluoropiperidin-1-yl)propyl)-4-methylpyridin-2-amine dihydrochloride, that exhibits excellent potency for rat (K

Indexed as

AminopyridinesNitric OxideAnimalsEnzyme InhibitorsHumansNitric Oxide SynthaseNitric Oxide Synthase Type IProtein IsoformsRatsalpha-aminopyridineAminopyridinesEnzyme InhibitorsNitric OxideNitric Oxide SynthaseNitric Oxide Synthase Type IProtein Isoforms2-AminopyridinesBlood-brain barrierFluorineMolecular rigidityNeurodegenerationNitric oxideNitric oxide synthasesPAMPA-BBB penetration

Identifiers

PMID35772285
PMCPMC9574886
OpenAlexW4283777932

What OpenQuestion holds

Textmetadata
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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.