RTI uses cookies to offer you the best experience online. By clicking “accept” on this website, you opt in and you agree to the use of cookies. If you would like to know more about how RTI uses cookies and how to manage them please view our Privacy Policy here. You can “opt out” or change your mind by visiting: http://optout.aboutads.info/. Click “accept” to agree.
The discovery of a potent series of carboxamide TRPA1 antagonists
Pryde, D. C., Marron, B., West, C. G., Reister, S., Amato, G., Yoger, K., Padilla, K., Turner, J., Swain, N. A., Cox, P. J., Skerratt, S. E., Ryckmans, T., Blakemore, D. C., Warmus, J., & Gerlach, A. C. (2016). The discovery of a potent series of carboxamide TRPA1 antagonists. MedChemComm, 7(11), 2145-2158. https://doi.org/10.1039/c6md00387g
A series of potent and selective carboxamide TRPA1 antagonists were identified by a high throughput screen. Structure-activity relationship studies around this series are described, resulting in a highly potent example of the series. Pharmacokinetic and skin flux data are presented for this compound. Efficacy was observed in a topical cinnamaldehyde flare study, providing a topical proof of pharmacology for this mechanism. These data suggest TRPA1 antagonism could be a viable mechanism to treat topical conditions such as atopic dermatitis.