The discovery of a potent series of carboxamide TRPA1 antagonists12. Issue 11 (7th September 2016)

• Record Type: Journal Article
• Authors: 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.
• Is Part Of: MedChemComm. Volume 7:Issue 11(2016:Nov.)
• Page Start: 2145
• Page End: 2158
• Publication Date: 2016-09-07
• Subjects: Pharmaceutical chemistry -- Periodicals; 615.19
• DOI: 10.1039/c6md00387g
• Languages: English
• ISSNs: 2040-2503

Abstract

Abstract : Potent and selective carboxamide TRPA1 antagonists were identified by high throughput screening, with efficacy demonstrated in a topical inflammation model. Abstract : 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.