Oxime derivatives related to AP18: Agonists and antagonists of the TRPA1 receptor

  • Bioorg Med Chem Lett. 2010 Jan 1;20(1):276-9. doi: 10.1016/j.bmcl.2009.10.113.
Jeff Defalco  1 ,  Daniel Steiger ,  Amy Gustafson ,  Daniel E Emerling ,  Michael G Kelly ,  Matthew A J Duncton
Affiliations
  • 1. Renovis, Inc. (a wholly-owned subsidiary of Evotec AG), Two Corporate Drive, South San Francisco, CA 94080, USA. [email protected]
PMID: 19945872 DOI: 10.1016/j.bmcl.2009.10.113
Abstract

AP18 1 was recently disclosed as an antagonist of the TRPA1 receptor by the research group of Patapoutian. However, no detailed structure-activity relationships around 1 have been disclosed. Thus, a small number of oximes related to AP18 were examined in order to characterize the determinants of TRPA1 activity. Congeners of AP18 were found to possess both agonist and antagonist activity, suggesting that AP18 may behave as a covalent antagonist of the TRPA1 ion-channel.