Oxime derivatives related to AP18: Agonists and antagonists of the TRPA1 receptor.
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.
Defalco
Jeff
J
Renovis, Inc. (a wholly-owned subsidiary of Evotec AG), Two Corporate Drive, South San Francisco, CA 94080, USA. jeff.defalco@gmail.com
Steiger
Daniel
D
Gustafson
Amy
A
Emerling
Daniel E
DE
Kelly
Michael G
MG
Duncton
Matthew A J
MA
D015220:Calcium Channels / Q000378:metabolism; D006801:Humans; D009419:Nerve Tissue Proteins / Q000819:agonists* / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010091:Oximes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels / Q000819:agonists* / Q000037:antagonists & inhibitors* / Q000378:metabolism
D015220:Calcium Channels; D009419:Nerve Tissue Proteins; D010091:Oximes; D000074025:TRPA1 Cation Channel; C473350:TRPA1 protein, human; D050051:Transient Receptor Potential Channels