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Bioorg Med Chem Lett ; 24(24): 5558-5562, 2014 Dec 15.
Article in English | MEDLINE | ID: mdl-25466174

ABSTRACT

Herewith, we report the design and synthesis of a series of N-(2-oxo-2((4-oxo-2-substituted thiazolidin-3yl)amino)ethyl) benzamide derivatives 7(a-j) under microwave irradiation, based on four component pharmacophoric model to get structural prerequisite indispensable for anticonvulsant activity. The synthesized derivatives were investigated in maximal electroshock seizure (MES), subcutaneous pentylenetetrazole (sc-PTZ) induced seizure and neurotoxicity screening. All the test compounds were administered at a dose of 30, 100 and 300 mg/kg body weight at the time interval of 0.5 h and 4 h. The compounds were also evaluated for behavioral activity and toxicity study. The compound 7 h was found to be most active in MES model. The anticonvulsant screening data shows that 65% of the compounds were found active against MES model when compared to 35% sc-PTZ model. The computational parameter such as docking study, logP determination and ADME prediction were performed to exploit the results.


Subject(s)
Anticonvulsants/chemical synthesis , Benzamides/chemistry , Microwaves , Animals , Anticonvulsants/pharmacology , Anticonvulsants/therapeutic use , Benzamides/pharmacokinetics , Benzamides/therapeutic use , Binding Sites , Disease Models, Animal , Half-Life , Liver/pathology , Mice , Molecular Docking Simulation , Motor Activity/drug effects , Protein Structure, Tertiary , Seizures/drug therapy , Sodium Channels/chemistry , Sodium Channels/metabolism , Thiazolidines/chemistry
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