On March 5, 2020, Focken, Thilo; Andrez, Jean-Christophe; Burford, Kristen Nicole; Dehnhardt, Christoph Martin; Grimwood, Michael Edward; Jia, Qi; Lofstrand, Verner Alexander; Wilson, Michael Scott; Zenova, Alla Yurevna; Wesolowski, Steven Sigmund; Sun, Shaoyi published a patent.Electric Literature of 1261686-95-6 The title of the patent was Preparation of heteroaryl-substituted sulfonamide compounds and their use as sodium channel inhibitors. And the patent contained the following:
This invention is directed to pyridine- and thiophene-sulfonamide compounds of formula I, as stereoisomers, enantiomers, tautomers thereof or mixtures thereof; or pharmaceutically acceptable salts, solvates or prodrugs thereof, for the treatment of diseases or conditions associated with voltage-gated sodium channels, such as epilepsy and/ or epileptic seizure disorders. Compounds of formula I wherein A is (un)substituted pyridinediyl, (un)substituted thiophenediyl, (un)substituted thiazolediyl, etc.; R1 is (un)substituted aryl and (un)substituted (mono/bi)cyclic heteroaryl; R2 is (un)substituted 5- to 6-membered heteroaryl; R3 and R4 are independently H and alkyl; and individual stereoisomers, enantiomers, tautomers, mixtures, pharmaceutically acceptable salts, solvates and prodrugs thereof, are claimed. Example compound II was prepared by sulfamidation of 5,6-dichloropyridine-3-sulfonyl chloride with tert-Bu thiazol-4-ylcarbamate; the resulting tert-Bu ((5,6-dichloropyridin-3-yl)sulfonyl)(thiazol-4-yl)carbamate underwent amination with (S)-1-(5-chloro-2-fluorophenyl)ethan-1-amine hydrochloride to give tert-Bu (S)-((5-chloro-6-((1-(5-chloro-2-fluorophenyl)ethyl)amino)pyridin-3-yl)sulfonyl)(thiazol-4-yl)carbamate, which underwent hydrolysis to give compound II. The invention compounds were evaluated for their sodium channel inhibitory activity. From the assay, it was determined that compound II exhibited IC50 values of 2.820μM, 5.573μM and 5.003μM towards Nav1.6, Nav1.5 and Nav1.1, resp. The experimental process involved the reaction of 2-(Bromomethyl)-6-fluorobenzonitrile(cas: 1261686-95-6).Electric Literature of 1261686-95-6
The Article related to heteroaryl sulfonamide preparation sodium channel inhibitor, Heterocyclic Compounds (More Than One Hetero Atom): Thiazoles, Isothiazoles and other aspects.Electric Literature of 1261686-95-6
Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts