Discovery of 12-thiazole abietanes as selective inhibitors of the human metabolic serine hydrolase hABHD16A

Ahonen, Tiina J. and Savinainen, Juha R. and Yli-Kauhaluoma, Jari and Kalso, Eija and Laitinen, Jarmo T. and Moreira, Vânia M. (2018) Discovery of 12-thiazole abietanes as selective inhibitors of the human metabolic serine hydrolase hABHD16A. ACS Medicinal Chemistry Letters, 9 (12). pp. 1269-1273. ISSN 1948-5875 (https://doi.org/10.1021/acsmedchemlett.8b00442)

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Abstract

Screening of an in-house library of compounds identified 12-thiazole abietanes as a new class of reversible inhibitors of the human metabolic serine hydrolase. Further optimization of the first hit compound lead to the 2-methylthiazole derivative 18, with an IC50 value of 3.4 ± 0.2 µM and promising selectivity. ABHD16A has been highlighted as a new target for in-flammation-mediated pain, although selective inhibitors of hABHD16A (human ABHD16A) have not yet been reported. Our study presents abietane-type diterpenoids as an attractive starting point for the design of selective ABHD16A inhibitors, which will contribute towards understanding the significance of hABHD16A inhibition in vivo.

ORCID iDs

Ahonen, Tiina J., Savinainen, Juha R., Yli-Kauhaluoma, Jari, Kalso, Eija, Laitinen, Jarmo T. and Moreira, Vânia M. ORCID logoORCID: https://orcid.org/0000-0001-6169-5035;
  • Item type:Article
    ID code:66299
    Dates:
    Date
    Event
    13 November 2018
    Published
    13 November 2018
    Published Online
    13 November 2018
    Accepted
    Notes:This document is the Accepted Manuscript version of a Published Work that appeared in final form in ACS Medicinal Chemistry Letters, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/acsmedchemlett.8b00442.
    Keywords:dehydroabietic acid, hABHD16A inhibitor, lysophosphatidylserine, metabolic serine hydrolase, Pharmacy and materia medica, Biochemistry, Organic Chemistry, Drug Discovery
    Subjects:Medicine > Pharmacy and materia medica
    Department:Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
    Depositing user: Pure Administrator
    Date deposited:06 Dec 2018 10:04
    Last modified:28 Nov 2022 02:37
    Related URLs:
    URI:https://strathprints.strath.ac.uk/id/eprint/66299
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