title: Synthesis of 2,6-dicarbethoxy-3,5-diaryltetrahydro-1,4-thiazine-1,1-dioxide derivatives as potent anticonvulsant agents.
abstract: An efficient synthesis of 2,6-dicarbethoxy-3,5-diaryltetrahydro-1,4-thiazine-1,1-dioxide derivatives has been achieved under aqueous medium for the first time in good to excellent yields. All the synthesized compounds were tested for anticonvulsant activity using the maximal electroshock (MES), subcutaneous pentylenetetrazole (scPTZ) screens, which are the most broadly employed seizure models for early identification of candidate anticonvulsants. Their neurotoxicity was determined applying the rotarod test. Seven compounds 4a, 4d, 4f, 4h, 4o, 4p and 4q showed promising anticonvulsant activities in both models employed for anticonvulsant evaluation. The most active compound 4d showed the MES-induced seizures with ED50 value of 10.2 mg/kg and TD50 value of 288.6 mg/kg after intraperitoneal injection to mice, which provided compound 4d with a protective index (TD50/ED50) of 28.3 in the MES test.
authors.affiliation: Department of Chemistry, Mother Teresa Women's University, Kodaikanal 624 101, Tamil Nadu, India. Electronic address: edayam2004@gmail.com.
authors.forename: Naushad
authors.initials: N
authors.lastname: Edayadulla
authors.affiliation: Department of Natural Products Chemistry, School of Chemistry, Madurai Kamaraj University, Madurai 625 021, Tamil Nadu, India. Electronic address: npc_ramesh@yahoo.co.in.
authors.forename: Penugonda
authors.initials: P
authors.lastname: Ramesh
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D003499:Cyclic S-Oxides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004597:Electroshock; D007274:Injections, Intraperitoneal; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D010433:Pentylenetetrazole / Q000008:administration & dosage; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy*; D013329:Structure-Activity Relationship; D013843:Thiazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: C000610701:2,6-dicarbethoxy-3,5-bis(4-chlorophenyl)tetrahydro-1,4-thiazine-1,1-dioxide; D000927:Anticonvulsants; D003499:Cyclic S-Oxides; D013843:Thiazines; D010433:Pentylenetetrazole
keywords: Anticonvulsant; Epilepsy; Thiazine-1,1-dioxide derivatives; Water medium