Structure-activity relationships of the prototypical TRPM8 agonist icilin

Bioorg Med Chem Lett. 2015 Jun 1;25(11):2285-90. doi: 10.1016/j.bmcl.2015.04.032. Epub 2015 Apr 16.

Abstract

A series of structural analogues of the TRPM8 agonist icilin was prepared. The compounds were examined for their ability to exert agonist or antagonist effects in HEK-293 cells expressing the TRPM8 receptor. Most structural modifications of the icilin structure largely met with diminished TRPM8 agonist activity. Cinnamamide 'open-chain' analogs of icilin, however, demonstrated significant antagonistic actions at the TRPM8 receptor. Optimal potency (IC50=73 nM) was observed in the 3-iodo derivative 18l.

Keywords: Icilin; TRPM8; TRPV1; Thermo-TRP channels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • HEK293 Cells
  • Humans
  • Molecular Structure
  • Pyrimidinones / chemistry*
  • Pyrimidinones / pharmacology*
  • Structure-Activity Relationship
  • TRPM Cation Channels / agonists*

Substances

  • Pyrimidinones
  • TRPM Cation Channels
  • TRPM8 protein, human
  • icilin