Structure-activity relationships of cycloalkylamide derivatives as inhibitors of the soluble epoxide hydrolase

In Hae Kim, Yong Kyu Park, Bruce D. Hammock, Kosuke Nishi

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Structure-activity relationships of cycloalkylamide compounds as inhibitors of human sEH were investigated. When the left side of amide function was modified by a variety of cycloalkanes, at least a C6 like cyclohexane was necessary to yield reasonable inhibition potency on the target enzyme. In compounds with a smaller cycloalkane or with a polar group on the left side of amide function, no inhibition was observed. On the other hand, increased hydrophobicity dramatically improved inhibition potency. Especially, a tetrahydronaphthalene (20) effectively increased the potency. When a series of alkyl or aryl derivatives of cycloalkylamide were investigated to continuously optimize the right side of the amide pharmacophore, a benzyl moiety functionalized with a polar group produced highly potent inhibition. A nonsubstituted benzyl, alkyl, aryl, or biaryl structure present on the right side of the cycloalkylamide function induced a big decrease in inhibition potency. Also, the resulting potent cycloalkylamide (32) showed reasonable physical properties.

Original languageEnglish (US)
Pages (from-to)1752-1761
Number of pages10
JournalJournal of Medicinal Chemistry
Volume54
Issue number6
DOIs
StatePublished - Mar 24 2011

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Fingerprint Dive into the research topics of 'Structure-activity relationships of cycloalkylamide derivatives as inhibitors of the soluble epoxide hydrolase'. Together they form a unique fingerprint.

  • Cite this