Evidence map›Paper›PMID 31668424›Full record

ArticleBioorganic & medicinal chemistry letters2019

An anthrone-based Kv7.2/7.3 channel blocker with improved properties for the investigation of psychiatric and neurodegenerative disorders.

Jacob D Porter, Oscar Vivas, C David Weaver, Abdulmohsen Alsafran, Elliot DiMilo, Leggy A Arnold, Eamonn J Dickson, Chris Dockendorff

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Bioorganic & medicinal chemistry letters, 2019. 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
–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

3 citing papers in PubMed.

  1. The pyridazine heterocycle in molecular recognition and drug discovery.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2023
    Review
  2. Chemical modulation of Kv7 potassium channels.RSC medicinal chemistry · 2021
    Review
  3. 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.

Jacob D PorterDepartment of Chemistry, Marquette University, P.O. Box 1881, Milwaukee, WI 53201-1881, USA.
Oscar VivasDepartment of Physiology & Membrane Biology, University of California, 1 Shields Avenue, Davis, CA 95616, USA.
C David WeaverDepartments of Pharmacology and Chemistry, Vanderbilt University, Vanderbilt Institute of Chemical Biology, Nashville, TN 37232, USA.
Abdulmohsen AlsafranDepartment of Chemistry, Marquette University, P.O. Box 1881, Milwaukee, WI 53201-1881, USA.
Elliot DiMiloDepartment of Chemistry and Biochemistry, Milwaukee Institute for Drug Discovery, University of Wisconsin, Milwaukee, WI 53211, USA.
Leggy A ArnoldDepartment of Chemistry and Biochemistry, Milwaukee Institute for Drug Discovery, University of Wisconsin, Milwaukee, WI 53211, USA.
Eamonn J DicksonDepartment of Physiology & Membrane Biology, University of California, 1 Shields Avenue, Davis, CA 95616, USA.
Chris DockendorffDepartment of Chemistry, Marquette University, P.O. Box 1881, Milwaukee, WI 53201-1881, USA. Electronic address: christopher.dockendorff@mu.edu.

Funding

Membrane contact sites regulate cellular excitabilityR01GM127513 · NIGMS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI DICKSON, EAMONN JAMES · 2019 to 2023
$1.6M
Fluorescent and Luminescent Kinetic Imaging Plate ReaderS10OD021734 · OD · VANDERBILT UNIVERSITY · PI LINDSLEY, CRAIG · 2016 to 2016
$671k
NIGMS NIH HHS R01 GM127513NIH HHS S10 OD021734NIMH NIH HHS HHSN271201300017C
6 · The paper itself

Abstract

A set of novel Kv7.2/7.3 (KCNQ2/3) channel blockers was synthesized to address several liabilities of the known compounds XE991 (metabolic instability and CYP inhibition) and the clinical compound DMP 543 (acid instability, insolubility, and lipophilicity). Using the anthrone scaffold of the prior channel blockers, alternative heteroarylmethyl substituents were installed via enolate alkylation reactions. Incorporation of a pyridazine and a fluorinated pyridine gave an analog (compound 18, JDP-107) with a promising combination of potency (IC

Indexed as

AnthracenesAnthronesDose-Response Relationship, DrugKCNQ2 Potassium ChannelKCNQ3 Potassium ChannelMental DisordersMolecular StructureNeurodegenerative DiseasesPotassium Channel BlockersStructure-Activity RelationshipAnthracenesanthroneAnthronesKCNQ2 Potassium ChannelKCNQ2 protein, humanKCNQ3 Potassium ChannelKCNQ3 protein, humanPotassium Channel BlockersDMP 543JDP-107Kv7 blockerSchizophreniaVoltage-gated potassium channel

Identifiers

PMID31668424
PMCPMC6858848

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.