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

Jeff Defalco; Daniel Steiger; Amy Gustafson; Daniel E Emerling; Michael G Kelly; Matthew A J Duncton

doi:10.1016/j.bmcl.2009.10.113

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. Epub 2009 Oct 30.

Authors

Jeff Defalco¹, Daniel Steiger, Amy Gustafson, Daniel E Emerling, Michael G Kelly, Matthew A J Duncton

Affiliation

¹ Renovis, Inc. (a wholly-owned subsidiary of Evotec AG), Two Corporate Drive, South San Francisco, CA 94080, USA. jeff.defalco@gmail.com

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.

MeSH terms

Calcium Channels / metabolism
Humans
Nerve Tissue Proteins / agonists*
Nerve Tissue Proteins / antagonists & inhibitors*
Nerve Tissue Proteins / metabolism
Oximes / chemical synthesis
Oximes / chemistry*
Oximes / pharmacology
Structure-Activity Relationship
TRPA1 Cation Channel
Transient Receptor Potential Channels / agonists*
Transient Receptor Potential Channels / antagonists & inhibitors*
Transient Receptor Potential Channels / metabolism

Substances

Calcium Channels
Nerve Tissue Proteins
Oximes
TRPA1 Cation Channel
TRPA1 protein, human
Transient Receptor Potential Channels