PubMed 22868228

Referenced in Channelpedia wiki pages of: none

Automatically associated channels: TRP , TRPA , TRPA1

Title: N-1-Alkyl-2-oxo-2-aryl amides as novel antagonists of the TRPA1 receptor.

Authors: Karl S A Vallin, Karin J Sterky, Eva Nyman, Jenny Bernström, Rebecka From, Christian Linde, Alexander B E Minidis, Andreas Nolting, Katja Närhi, Ellen M Santangelo, Fernando W Sehgelmeble, Daniel Sohn, Jennie Strindlund, Dirk Weigelt

Journal, date & volume: Bioorg. Med. Chem. Lett., 2012 Sep 1 , 22, 5485-92

PubMed link:

A series of potent antagonists of the ion channel transient receptor potential A1 (TRPA1) was developed by modifying lead structure 16 that was discovered by high-throughput screening. Based on lead compound 16, a SAR was established, showing a narrow region at the nitro-aromatic R(1) moiety and at the warhead, while the R(2) side had a much wider scope including ureas and carbamates. Compound 16 inhibits Ca(2+)-activated TRPA1 currents reversibly in whole cell patch clamp experiments, indicating that under in vivo conditions, it does not react covalently, despite its potentially electrophilic ketone.