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.
- dehydroabietic acid
- hABHD16A inhibitor
- metabolic serine hydrolase
Ahonen, T. J., Savinainen, J. R., Yli-Kauhaluoma, J., Kalso, E., Laitinen, J. T., & Moreira, V. M. (2018). Discovery of 12-thiazole abietanes as selective inhibitors of the human metabolic serine hydrolase hABHD16A. ACS Medicinal Chemistry Letters , 9(12), 1269-1273. https://doi.org/10.1021/acsmedchemlett.8b00442