Structure-activity relationships of substituted oxyoxalamides as inhibitors of the human soluble epoxide hydrolase

In Hae Kim, In Hee Lee, Hisashi Nishiwaki, Bruce D. Hammock, Kosuke Nishi

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


We explored both structure-activity relationships among substituted oxyoxalamides used as the primary pharmacophore of inhibitors of the human sEH and as a secondary pharmacophore to improve water solubility of inhibitors When the oxyoxalamide function was modified with a variety of alkyls or substituted alkyls, compound 6 with a 2-adamantyl group and a benzyl group was found to be a potent sEH inhibitor, suggesting that the substituted oxyoxalamide function is a promising primary pharmacophore for the human sEH, and compound 6 can be a novel lead structure for the development of further improved oxyoxalamide or other related derivatives In addition, introduction of substituted oxyoxalamide to inhibitors with an amide or urea primary pharmacophore produced significant improvements in inhibition potency and water solubility In particular, the N,N,O-trimethyloxyoxalamide group in amide or urea inhibitors (26 and 31) was most effective among those tested for both inhibition and solubility The results indicate that substituted oxyoxalamide function incorporated into amide or urea inhibitors is a useful secondary pharmacophore, and the resulting structures will be an important basis for the development of bioavailable sEH inhibitors

Original languageEnglish (US)
Pages (from-to)1163-1175
Number of pages13
JournalBioorganic and Medicinal Chemistry
Issue number3
StatePublished - Feb 1 2014


  • Human soluble epoxide hydrolase
  • Inhibitors
  • Substituted oxyoxalamides

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry
  • Biochemistry


Dive into the research topics of 'Structure-activity relationships of substituted oxyoxalamides as inhibitors of the human soluble epoxide hydrolase'. Together they form a unique fingerprint.

Cite this