115169-77-2Relevant articles and documents
Tetrahydrofuran-Based Transient Receptor Potential Ankyrin 1 (TRPA1) Antagonists: Ligand-Based Discovery, Activity in a Rodent Asthma Model, and Mechanism-of-Action via Cryogenic Electron Microscopy
Terrett, Jack A.,Chen, Huifen,Shore, Daniel G.,Villemure, Elisia,Larouche-Gauthier, Robin,Déry, Martin,Beaumier, Francis,Constantineau-Forget, Léa,Grand-Ma?tre, Chantal,Lépissier, Luce,Ciblat, Stéphane,Sturino, Claudio,Chen, Yong,Hu, Baihua,Lu, Aijun,Wang, Yunli,Cridland, Andrew P.,Ward, Stuart I.,Hackos, David H.,Reese, Rebecca M.,Shields, Shannon D.,Chen, Jun,Balestrini, Alessia,Riol-Blanco, Lorena,Lee, Wyne P.,Liu, John,Suto, Eric,Wu, Xiumin,Zhang, Juan,Ly, Justin Q.,La, Hank,Johnson, Kevin,Baumgardner, Matt,Chou, Kang-Jye,Rohou, Alexis,Rougé, Lionel,Safina, Brian S.,Magnuson, Steven,Volgraf, Matthew
, p. 3843 - 3869 (2021/05/04)
Transient receptor potential ankyrin 1 (TRPA1) is a nonselective calcium-permeable ion channel highly expressed in the primary sensory neurons functioning as a polymodal sensor for exogenous and endogenous stimuli and has generated widespread interest as a target for inhibition due to its implication in neuropathic pain and respiratory disease. Herein, we describe the optimization of a series of potent, selective, and orally bioavailable TRPA1 small molecule antagonists, leading to the discovery of a novel tetrahydrofuran-based linker. Given the balance of physicochemical properties and strong in vivo target engagement in a rat AITC-induced pain assay, compound 20 was progressed into a guinea pig ovalbumin asthma model where it exhibited significant dose-dependent reduction of inflammatory response. Furthermore, the structure of the TRPA1 channel bound to compound 21 was determined via cryogenic electron microscopy to a resolution of 3 ?, revealing the binding site and mechanism of action for this class of antagonists.
OXADIAZOLONES AS TRANSIENT RECEPTOR POTENTIAL CHANNEL INHIBITORS
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Paragraph 0681-0684; 0719-0722, (2018/06/12)
The invention relates to compounds of formula (I) and pharmaceutically acceptable salts thereof. In addition, the present invention relates to methods of manufacturing and methods of using the compounds of formula (I) as well as pharmaceutical compositions containing such compounds. The compounds may be useful in treating diseases and conditions mediated by TRPA1, such as pain.
N-heterocyclic carbene-rhodium(I) complexes derived from proline for the 1,4-conjugate addition of arylboronic acids to enones in neat water
Tang, Yi-Qiang,Lv, Huan,He, Xiao-Na,Lu, Jian-Mei,Shao, Li-Xiong
experimental part, p. 705 - 708 (2012/01/07)
N-Heterocyclic carbene-rhodium(I) complexes derived from N-benzyl substituted proline have been successfully synthesized and were found to be efficient catalysts for the 1,4-conjugate addition of arylboronic acids to enones in neat water at 40 °C. Under the optimal reaction conditions, all reactions gave the addition products in good to high yields.
