Evidence map›Paper›PMID 34118412›Full record

ArticleBioorganic & medicinal chemistry letters2021

Discovery of a novel class of heteroaryl-pyrrolidinones as positive allosteric modulators of the muscarinic acetylcholine receptor M

Paul K Spearing, Hyekyung P Cho, Vincent B Luscombe, Anna L Blobaum, Olivier Boutaud, Darren W Engers, Alice L Rodriguez, Colleen M Niswender, P Jeffrey Conn, Craig W Lindsley and 1 more

Abstract read
In one paragraph

Article in Bioorganic & medicinal chemistry letters, 2021. 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. 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

11 authors.

Paul K SpearingWarren Center for Neuroscience Drug Discovery, Nashville, TN 37232, United States; Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232, United States.
Hyekyung P ChoWarren Center for Neuroscience Drug Discovery, Nashville, TN 37232, United States; Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232, United States.
Vincent B LuscombeWarren Center for Neuroscience Drug Discovery, Nashville, TN 37232, United States; Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232, United States.
Anna L BlobaumWarren Center for Neuroscience Drug Discovery, Nashville, TN 37232, United States; Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232, United States.
Olivier BoutaudWarren Center for Neuroscience Drug Discovery, Nashville, TN 37232, United States; Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232, United States.
Darren W EngersWarren Center for Neuroscience Drug Discovery, Nashville, TN 37232, United States; Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232, United States.
Alice L RodriguezWarren Center for Neuroscience Drug Discovery, Nashville, TN 37232, United States; Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232, United States.
Colleen M NiswenderWarren Center for Neuroscience Drug Discovery, Nashville, TN 37232, United States; Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232, United States; Vanderbilt Kennedy Center, Vanderbilt University School of Medicine, Nashville, TN 37232, United States.
P Jeffrey ConnWarren Center for Neuroscience Drug Discovery, Nashville, TN 37232, United States; Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232, United States; Vanderbilt Kennedy Center, Vanderbilt University School of Medicine, Nashville, TN 37232, United States.
Craig W LindsleyWarren Center for Neuroscience Drug Discovery, Nashville, TN 37232, United States; Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232, United States; Department of Chemistry, Vanderbilt University, Nashville, TN 37232, United States; Department of Biochemistry, Vanderbilt University, Nashville, TN 37232, United States.
Aaron M BenderWarren Center for Neuroscience Drug Discovery, Nashville, TN 37232, United States; Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232, United States. Electronic address: aaron.bender@vanderbilt.edu.

Funding

Safety and tolerability testing of VU0467319: an M1 PAM for clinical developmentU19MH106839 · NIMH · VANDERBILT UNIVERSITY · PI CONN, P JEFFREY · 2015 to 2017
$5.3M
Selective M1 mAChR allosteric modulators for the treatment of schizophreniaR01MH082867 · NIMH · VANDERBILT UNIVERSITY · PI LINDSLEY, CRAIG · 2008 to 2017
$3.7M
NIMH NIH HHS R01 MH082867NIMH NIH HHS U19 MH106839
6 · The paper itself

Abstract

This Letter describes the synthesis and optimization of a series of heteroaryl-pyrrolidinone positive allosteric modulators (PAMs) of the muscarinic acetylcholine receptor M

Indexed as

Drug DiscoveryAllosteric RegulationAnimalsDose-Response Relationship, DrugHumansMolecular StructurePyrrolidinonesRatsReceptor, Muscarinic M1Structure-Activity RelationshipPyrrolidinonesReceptor, Muscarinic M1Muscarinic acetylcholine receptorPositive allosteric modulatorStructure-activity relationship

Identifiers

PMID34118412
PMCPMC8349895

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.