Discovery of 1 H- Pyrazole Biaryl Sulfonamides as Novel G2019S-LRRK2 Kinase Inhibitors

G2019S (GS) is the most prevalent mutation in the leucine rich repeat protein kinase 2 gene ( ), a genetic predisposition that is common for Parkinson's disease, as well as for some forms of cancer, and is a shared risk allele for Crohn's disease. GS-LRRK2 has a hyperactive kinase, and alt...

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Bibliographic Details
Published in:ACS medicinal chemistry letters 2022-06, Vol.13 (6), p.981-988
Main Authors: Leśniak, Robert K, Nichols, R Jeremy, Schonemann, Marcus, Zhao, Jing, Gajera, Chandresh R, Lam, Grace, Nguyen, Khanh C, Langston, J William, Smith, Mark, Montine, Thomas J
Format: Article
Language:English
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Summary:G2019S (GS) is the most prevalent mutation in the leucine rich repeat protein kinase 2 gene ( ), a genetic predisposition that is common for Parkinson's disease, as well as for some forms of cancer, and is a shared risk allele for Crohn's disease. GS-LRRK2 has a hyperactive kinase, and although numerous drug discovery programs have targeted LRRK2 kinase, few have reached clinical development. We report the discovery and preliminary development of an entirely novel structural class of potent and selective GS-LRRK2 kinase inhibitors: biaryl-1 -pyrazoles.
ISSN:1948-5875
1948-5875
DOI:10.1021/acsmedchemlett.2c00116