Evidence map›Paper›PMID 38199328›Full record

ArticleBioorganic & medicinal chemistry letters2024

Identification of 4-(6-((2-methoxyphenyl)amino)pyrazin-2-yl)benzoic acids as CSNK2A inhibitors with antiviral activity and improved selectivity over PIM3.

Kareem A Galal, Andreas Krämer, Benjamin G Strickland, Jeffery L Smith, Rebekah J Dickmander, Nathaniel J Moorman, Timothy M Willson

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Bioorganic & medicinal chemistry letters, 2024. 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

5 · Who and what money

Authors and funding

7 authors.

Kareem A GalalStructural Genomics Consortium, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Rapidly Emerging Antiviral Drug Development Initiative (READDI), Chapel Hill, NC 27599, USA.
Andreas KrämerStructural Genomics Consortium, Buchmann Institute for Life Sciences, Goethe University Frankfurt, Max-von-Laue-Strabe 15, Frankfurt 60438, Germany; Institute of Pharmaceutical Chemistry, Goethe University Frankfurt, Max-von-Laue-Strabe 9, Frankfurt 60438, Germany; Frankfurt Cancer Institute, Paul-Ehrlich-Straße 42-44, Frankfurt 60596, Germany.
Benjamin G StricklandStructural Genomics Consortium, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Jeffery L SmithStructural Genomics Consortium, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Rebekah J DickmanderRapidly Emerging Antiviral Drug Development Initiative (READDI), Chapel Hill, NC 27599, USA; Department of Microbiology & Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Nathaniel J MoormanRapidly Emerging Antiviral Drug Development Initiative (READDI), Chapel Hill, NC 27599, USA; Department of Microbiology & Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Timothy M WillsonStructural Genomics Consortium, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Rapidly Emerging Antiviral Drug Development Initiative (READDI), Chapel Hill, NC 27599, USA. Electronic address: tim.willson@unc.edu.

Funding

Illuminating Function of the Understudied Druggable KinomeU24DK116204 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI JOHNSON, GARY L. · 2017 to 2022
$13.6M
NIDDK NIH HHS U24 DK116204
6 · The paper itself

Abstract

We report the synthesis of 2,6-disubstituted pyrazines as potent cell active CSNK2A inhibitors. 4'-Carboxyphenyl was found to be the optimal 2-pyrazine substituent for CSNK2A activity, with little tolerance for additional modification. At the 6-position, modifications of the 6-isopropylaminoindazole substituent were explored to improve selectivity over PIM3 while maintaining potent CSNK2A inhibition. The 6-isopropoxyindole analogue 6c was identified as a nanomolar CSNK2A inhibitor with 30-fold selectivity over PIM3 in cells. Replacement of the 6-isopropoxyindole by isosteric ortho-methoxy anilines, such as 7c, generated analogues with selectivity for CSNK2A over PIM3 and improved the kinome-wide selectivity. The optimized 2,6-disubstituted pyrazines showed inhibition of viral replication consistent with their CSNK2A activity.

Indexed as

BenzoatesPyrazinesAntiviral AgentsStructure-Activity RelationshipAntiviral AgentsBenzoatesPyrazines

Identifiers

PMID38199328
PMCPMC12151307

What OpenQuestion holds

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Registered trials

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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.