Discovery of 12-Thiazole Abietanes as Selective Inhibitors of the Human Metabolic Serine Hydrolase hABHD16A
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CitationAhonen, Tiina J. Savinainen, Juha R. Yli-Kauhaluoma, Jari: Kalso, Eija. Laitinen, Jarmo T. 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) , 1269–1273. 10.1021/acsmedchemlett.8b00442.
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 inflammation-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 toward understanding the significance of hABHD16A inhibition in vivo.
Subjectsdehydroabietic acid hABHD16A inhibitor lysophosphatidylserine metabolic serine hydrolase
Link to the original itemhttp://dx.doi.org/10.1021/acsmedchemlett.8b00442
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