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 mu M 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.

Original languageEnglish
JournalACS Medicinal Chemistry Letters
Issue number12
Pages (from-to)1269-1273
Number of pages9
Publication statusPublished - 13 Dec 2018
MoE publication typeA1 Journal article-refereed

Fields of Science

  • dehydroabietic acid
  • hABHD16A inhibitor
  • lysophosphatidylserine
  • metabolic serine hydrolase
  • 317 Pharmacy
  • 116 Chemical sciences

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