N-alkyl-[1,1′-biphenyl]-2-sulfonamide derivatives as novel broad spectrum anti-epileptic drugs with efficacy equivalent to that of sodium valproate

• Published in: Bioorganic & medicinal chemistry letters Vol. 27; no. 17; pp. 4118 - 4121
• Main Authors: Tanaka, Tomoyuki, Yajima, Nana, Kiyoshi, Tomoko, Miura, Yoshiki, Iwama, Seiji
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 01.09.2017; Elsevier
• Subjects: 1,1′-Biphenyl-2-sulfonamide; Animals; Anticonvulsants - chemical synthesis; Anticonvulsants - chemistry; Anticonvulsants - pharmacology; Chemistry; Chemistry, Medicinal; Chemistry, Organic; Disease Models, Animal; Dose-Response Relationship, Drug; Epilepsy; Epilepsy - drug therapy; In vivo screening; Life Sciences & Biomedicine; MES; Mice; Molecular Structure; Pharmacology & Pharmacy; Physical Sciences; PTZ; Rats; Science & Technology; Structure-Activity Relationship; Sulfonamides - chemical synthesis; Sulfonamides - chemistry; Sulfonamides - pharmacology; Valproic Acid - chemical synthesis; Valproic Acid - chemistry; Valproic Acid - pharmacology; 1,1′-Biphenyl-2-sulfonamide; MES; Epilepsy; PTZ; In vivo screening; 1,1'-Biphenyl-2-sulfonamide; MODELS
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2017.07.037

[Display omitted] In order to develop phenyl sulfonamides as a novel class of anti-epileptic drugs (AED) for both general and partial seizure, we initiated in vivo screening of our chemical library in the mice MES and sc-PTZ models and found compounds 1 and 2 as lead compounds. Optimization of 1 and 2 led to the discovery of compound 21, which showed potent anticonvulsant effect in MES, scPTZ and rat amygdala kindling models. These findings indicate that compound 21 could be a useful new broad spectrum AED like sodium valproate and provide an opportunity to struggle current therapy-resistant epilepsy.