Discovery and development of a novel class of phenoxyacetyl amides as highly potent TRPM8 agonists for use as cooling agents

  • Bioorg Med Chem Lett. 2017 Aug 15;27(16):3931-3938. doi: 10.1016/j.bmcl.2017.04.003.
Alain Noncovich  1 ,  Chad Priest  2 ,  Jane Ung  1 ,  Andrew P Patron  1 ,  Guy Servant  1 ,  Paul Brust  1 ,  Nicole Servant  1 ,  Nathan Faber  1 ,  Hanghui Liu  1 ,  Nicole S Gonsalves  1 ,  Tanya L Ditschun  1
Affiliations
  • 1. Senomyx Inc., 4767 Nexus Centre Dr, San Diego, CA 92121, United States.
  • 2. Senomyx Inc., 4767 Nexus Centre Dr, San Diego, CA 92121, United States. Electronic address: [email protected].
PMID: 28662813 DOI: 10.1016/j.bmcl.2017.04.003
Abstract

The paper presents the activity trends for a novel series of phenoxyacetyl amides as human TRPM8 receptor agonists. This series encompasses in vitro activity values ranging from the micromolar to the picomolar levels. Sensory evaluation of these molecules highlights their relevance as cooling agents for oral applications. The positive outcome of the complete evaluation of N-(1H-pyrazol-3-yl)-N-(thiophen-2-ylmethyl)-2-(p-tolyloxy)acetamide resulted in its approval for Generally Recognized As Safe (GRAS) status by the Flavor & Extract Manufacturer Association (FEMA) as FEMA 4809.

Keywords
Chemesthesis; Coolants; Cooling agents; FEMA 4809; Menthol; TRPM8 agonists; WS-3.
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