On November 14, 2019, Focken, Thilo; Burford, Kristen; Grimwood, Michael E.; Zenova, Alla; Andrez, Jean-Christophe; Gong, Wei; Wilson, Michael; Taron, Matt; Decker, Shannon; Lofstrand, Verner; Chowdhury, Sultan; Shuart, Noah; Lin, Sophia; Goodchild, Samuel J.; Young, Clint; Soriano, Maegan; Tari, Parisa K.; Waldbrook, Matthew; Nelkenbrecher, Karen; Kwan, Rainbow; Lindgren, Andrea; de Boer, Gina; Lee, Stephanie; Sojo, Luis; DeVita, Robert J.; Cohen, Charles J.; Wesolowski, Steven S.; Johnson, J. P.; Dehnhardt, Christoph M.; Empfield, James R. published an article.Computed Properties of 1261686-95-6 The title of the article was Identification of CNS-Penetrant Aryl Sulfonamides as Isoform-Selective NaV1.6 Inhibitors with Efficacy in Mouse Models of Epilepsy. And the article contained the following:
Nonselective antagonists of voltage-gated sodium (NaV) channels have been long used for the treatment of epilepsies. The efficacy of these drugs is thought to be due to the block of sodium channels on excitatory neurons, primarily NaV1.6 and NaV1.2. However, these currently marketed drugs require high drug exposure and suffer from narrow therapeutic indexes. Selective inhibition of NaV1.6, while sparing NaV1.1, is anticipated to provide a more effective and better tolerated treatment for epilepsies. In addition, block of NaV1.2 may complement the anticonvulsant activity of NaV1.6 inhibition. We discovered a novel series of aryl sulfonamides as CNS-penetrant, isoform-selective NaV1.6 inhibitors, which also displayed potent block of NaV1.2. Optimization focused on increasing selectivity over NaV1.1, improving metabolic stability, reducing active efflux, and addressing a pregnane X-receptor liability. We obtained compounds 30-32, which produced potent anticonvulsant activity in mouse seizure models, including a d.c. maximal electroshock seizure assay. The experimental process involved the reaction of 2-(Bromomethyl)-6-fluorobenzonitrile(cas: 1261686-95-6).Computed Properties of 1261686-95-6
The Article related to cns penetrant aryl sulfonamide preparation epilepsy odium channel, Pharmacology: Structure-Activity and other aspects.Computed Properties of 1261686-95-6
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