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 |
| |
| Affiliation: | 1. Medicinal Chemistry, CNSP iMed, AstraZeneca R&D, Innovative Medicines, SE-15185 Södertälje, Sweden;2. Discovery Sciences, AstraZeneca R&D, Innovative Medicines, SE-15185 Södertälje, Sweden;3. Discovery Sciences, AstraZeneca R&D, Innovative Medicines, SE-43183 Mölndal, Sweden;4. Neuroscience, CNSP iMed, AstraZeneca R&D, Innovative Medicines, SE-15185 Södertälje, Sweden |
| |
| Abstract: | ![]()
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. |
| |
| Keywords: | Ion channel TRPA1 Antagonist |
| 本文献已被 ScienceDirect PubMed 等数据库收录！ |
|
