Evidence map›Paper›PMID 37453616›Full record

ArticleBioorganic & medicinal chemistry letters2023

Optimizing metabolic stability of phosphodiesterase 5 inhibitors: Discovery of a potent N-(pyridin-3-ylmethyl)quinoline derivative targeting synaptic plasticity.

Elisa Zuccarello, Hong Zhang, Erica Acquarone, Dang Pham, Anna Staniszewski, Shi-Xian Deng, Donald W Landry, Ottavio Arancio, Jole Fiorito

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Bioorganic & medicinal chemistry letters, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.8field-weighted citation impact, top 27% 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

3 citing papers in PubMed, 5 citations in OpenAlex.

  1. Review
  2. Review
  3. 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

9 authors at 2 institutions in 1 country.

Elisa ZuccarelloTaub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, NY, United States; Department of Medicine, Columbia University, New York, NY, United States.
Hong ZhangTaub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, NY, United States.
Erica AcquaroneTaub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, NY, United States.
Dang PhamNew York Institute of Technology, Department of Biological and Chemical Sciences, Northern Boulevard, Old Westbury, NY 11568, United States.
Anna StaniszewskiTaub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, NY, United States.
Shi-Xian DengDepartment of Medicine, Columbia University, New York, NY, United States.
Donald W LandryDepartment of Medicine, Columbia University, New York, NY, United States.
Ottavio ArancioTaub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, NY, United States; Department of Medicine, Columbia University, New York, NY, United States; Department of Pathology and Cell Biology, Columbia University, New York, NY, United States.
Jole FioritoNew York Institute of Technology, Department of Biological and Chemical Sciences, Northern Boulevard, Old Westbury, NY 11568, United States; Department of Medicine, Columbia University, New York, NY, United States. Electronic address: jfiori01@nyit.edu.
Columbia University · USNew York Institute of Technology · US

Funding

The Role of SUMOylation in Tau-Mediated PathologyR01NS110024 · NINDS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI ARANCIO, OTTAVIO · 2019 to 2023
$2.0M
NINDS NIH HHS R01 NS110024
6 · The paper itself

Abstract

Phosphodiesterase 5 (PDE5) is a cyclic guanosine monophosphate-degrading enzyme involved in numerous biological pathways. Inhibitors of PDE5 are important therapeutics for the treatment of neurodegenerative diseases, including Alzheimer's disease (AD). We previously reported the first generation of quinoline-based PDE5 inhibitors for the treatment of AD. However, the short in vitro microsomal stability rendered them unsuitable drug candidates. Here we report a series of new quinoline-based PDE5 inhibitors. Among them, compound 4b, 8-cyclopropyl-3-(hydroxymethyl)-4-(((6-methoxypyridin-3-yl)methyl)amino)quinoline-6-carbonitrile, shows a PDE5 IC

Indexed as

Alzheimer DiseaseQuinolinesAnimalsCyclic Nucleotide Phosphodiesterases, Type 5MiceNeuronal PlasticityPhosphodiesterase 5 InhibitorsCyclic Nucleotide Phosphodiesterases, Type 5Phosphodiesterase 5 InhibitorsQuinolinescGMPHuman liver microsomesMetabolic stabilityPDE5 inhibitorsQuinoline derivativesTau protein

Identifiers

PMID37453616
PMCPMC10528936
OpenAlexW4384207891

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

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.