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)
Preview |
Text.
Filename: 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.
-
-
Item type: Article ID code: 66299 Dates: DateEvent13 November 2018Published13 November 2018Published Online13 November 2018AcceptedNotes: 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. 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: 14 Feb 2024 01:57 Related URLs: URI: https://strathprints.strath.ac.uk/id/eprint/66299