Synthesis, characterization, and pharmacological evaluation of new GABA analogs as potent anticonvulsant agents

Medicinal Chemistry Research
2012.0

Abstract

A series of new c-aminobutyric acid (GABA) derivatives was obtained from 4-(1,3-dioxoisoindolin-2 yl)butanoic acid by coupling it with various substituted amines by using DCC as coupling reagent. The compound 3 was synthesized by treating GABA and phthalimide at high temperature under anhydrous conditions. All the synthesized compounds were confirmed and characterized by using various spectral technique like (IR, 1 H NMR, 13C NMR, and mass spectroscopy) studies. Anticonvulsant evaluations of all the synthesized compounds were done by using various seizures models like maximal electroshockinduced seizure (MES), subcutaneous pentylenetetrazole (scPTZ), subcutaneous strychnine (scSTY), and intraperitoneal picrotoxin (ipPIC)-induced seizure threshold tests at a dose of 30, 100, and 300 mg/kg body weight and anticonvulsant activity was noted at 0.5 and 4 h time intervals after the drug administration. The compound 4a 4-(1,3 dioxoisoindolin-2-yl)-N-phenylbutanamide displayed weak anticonvulsant activity in MES test at a dose of 300 mg/kg. Analogs 4d, 4h, and 4m displayed promising activity in scPTZ seizures model. Most of the synthesized compounds were found to be effective in the scSTY and ipPIC models and very few compounds showed protection in the scPTZ model. Among all the tested compounds, 4h 4-(1,3-dioxoisoindolin-2-yl)-N-(4-ethylphenyl)butanamide showed protection in various seizures model except in the scSTY model, while analog 4d was found to be the most potent compound in scPTZ model showing protection at a dose of 30 mg/kg. Further all the compounds exhibited lesser neurotoxicity compared with standard drug. The essential structural features responsible for interaction with receptor site are established within a suggested pharmacophore.

Knowledge Graph

Similar Paper

Synthesis, characterization, and pharmacological evaluation of new GABA analogs as potent anticonvulsant agents
Medicinal Chemistry Research 2012.0
Synthesis and anticonvulsant activity of 4-(2-(2,6-dimethylphenylamino)-2-oxoethylamino)-N-(substituted)butanamides: A pharmacophoric hybrid approach
Bioorganic & Medicinal Chemistry Letters 2007.0
Synthesis of new piperidyl indanone derivatives as anticonvulsant agents
Medicinal Chemistry Research 2012.0
Design and synthesis of anticonvulsants from a combined phthalimide–GABA–anilide and hydrazone pharmacophore
European Journal of Medicinal Chemistry 2007.0
Synthesis, biological evaluation and structure–activity relationship of new GABA uptake inhibitors, derivatives of 4-aminobutanamides
European Journal of Medicinal Chemistry 2014.0
Phosphorus analogs of .gamma.-aminobutyric acid, a new class of anticonvulsants
Journal of Medicinal Chemistry 1984.0
Newer GABA derivatives for the treatment of epilepsy including febrile seizures: A bioisosteric approach
European Journal of Medicinal Chemistry 2008.0
Synthesis of 1,3,4-oxadiazole derivatives with anticonvulsant activity and their binding to the GABAA receptor
European Journal of Medicinal Chemistry 2020.0
Design, synthesis and anticonvulsant evaluation of N-(benzo[d]thiazol-2-ylcarbamoyl)-2-methyl-4-oxoquinazoline-3(4H)-carbothioamide derivatives: A hybrid pharmacophore approach
European Journal of Medicinal Chemistry 2013.0
Synthesis and anticonvulsant properties of new acetamide derivatives of phthalimide, and its saturated cyclohexane and norbornene analogs
European Journal of Medicinal Chemistry 2011.0