title: Design, synthesis and anticonvulsant activity of some new 6,8-halo-substituted-2h-[1,2,4]triazino[5,6-b]indole-3(5h)-one/-thione and 6,8-halo-substituted 5-methyl-2h-[1,2,4]triazino[5,6-b]indol-3(5h)-one/-thione.
abstract: A new series of 6,8-halo-substituted-2H-[1,2,4]triazino[5,6-b]indole-3(5H)-one/-thione and 6,8-halo-substituted 5-methyl-2H-[1,2,4]triazino[5,6-b]indol-3(5H)-one/-thione (5a-5l) were designed and synthesized keeping in view of the structural requirement of pharmacophore. The above compounds were characterized by thin layer chromatography and spectral analysis. Anticonvulsant activity of the synthesized compounds was evaluated by the maximal electroshock (MES) test. Neurotoxicity and CNS depressant effects were evaluated by the rotarod motor impairment and Porsolt's force swim tests, respectively. A computational study was carried out, for calculation of pharmacophore pattern, prediction of pharmacokinetic properties and toxicity properties. The above study revealed that the compounds 8-chloro-2H-[1,2,4]triazino[5,6-b]indol-3(5H)-one (5e), 6,8-dibromo-2H-[1,2,4]triazino[5,6-b]indol-3(5H)-one (5i) and 6,8-dibromo-5-methyl-2H-[1,2,4]triazino[5,6-b]indol-3(5H)-one (5k) possess excellent anticonvulsant activity in the series with little CNS depressant effect and no neurotoxicity as compared to standard drugs phenytoin and carbamazepine.
authors.affiliation: Dr. K. N. Modi Institute of Pharmaceutical Education and Research, Inside Cotton MillCompound, Modinagar, India.
authors.forename: Rajeev
authors.initials: R
authors.lastname: Kumar
authors.affiliation: Dr. K. N. Modi Institute of Pharmaceutical Education and Research, Inside Cotton MillCompound, Modinagar, India.
authors.forename: Tejendra
authors.initials: T
authors.lastname: Singh
authors.affiliation: Dr. K. N. Modi Institute of Pharmaceutical Education and Research, Inside Cotton MillCompound, Modinagar, India.
authors.forename: Hariram
authors.initials: H
authors.lastname: Singh
authors.affiliation: Department of Pharmaceutical Sciences, Guru Jambheshwar University of Science and Technology, Hisar (Haryana), India.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Jain
authors.affiliation: Dr. K. N. Modi Institute of Pharmaceutical Education and Research, Inside Cotton MillCompound, Modinagar, India.
authors.forename: R K
authors.initials: RK
authors.lastname: Roy
keywords: 1,2,4-triazine; anticonvulsant activity; computational study; neurotoxicity