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

[img]
Preview
 Text (Ahonen-etal-ACS-MCL-2018-Discovery-of-12-thiazole-abietanes-as-selective-inhibitors)
Ahonen_etal_ACS_MCL_2018_Discovery_of_12_thiazole_abietanes_as_selective_inhibitors.pdf
Accepted Author Manuscript
Download (344kB)| Preview

    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.

    Creators(s): 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
    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:21 Jan 2021 10:33
    Related URLs:
    URI:https://strathprints.strath.ac.uk/id/eprint/66299
    Export data:
    CORE (COnnecting REpositories)