title: Design and Synthesis of Novel Phenylpiperazine Derivatives as Potential Anticonvulsant Agents.
abstract: Eighteen new 5-benzylidene-3-(4-arylpiperazin-1-ylmethyl)-2-thioxo-imidazolidin-4-ones were designed as hybrid structures from previously reported anticonvulsant compounds, synthesized and tested for anticonvulsant activity. Initial anticonvulsant screening was performed using the strychnine (2 mg/kg IP) potent generalized-induced seizure and pentylenetetrazole (PTZ) (60 mg/kg IP) acute clonic-induced convulsion screens in mice. All the molecules were found to be effective in at least one seizure model, compounds 10, 13, 15, 17, and 18 were active against both types of seizures induced. Compound 13 turned out to be the most active candidate within the strychnine model, having an average survival time of 6 min close to that of the positive control phenytoin, while compound 8 showed 100% protection from the induced PTZ seizures, resembling the protection of the positive control phenobarbital. Initial SAR studies for anticonvulsant activity are discussed.
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo, Egypt.
authors.forename: Monica M W
authors.initials: MM
authors.lastname: Habib
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo, Egypt.|American University of The Middle East, Egaila, Kuwait.
authors.forename: Mohamed A O
authors.initials: MA
authors.lastname: Abdelfattah
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo, Egypt.
authors.forename: Ashraf H
authors.initials: AH
authors.lastname: Abadi
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology; D004195:Disease Models, Animal; D015195:Drug Design; D008297:Male; D051379:Mice; D015394:Molecular Structure; D010433:Pentylenetetrazole; D010634:Phenobarbital / Q000494:pharmacology; D010879:Piperazines / Q000138:chemical synthesis* / Q000494:pharmacology*; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D013329:Structure-Activity Relationship; D013331:Strychnine
chemical_list: D000927:Anticonvulsants; D010879:Piperazines; D013331:Strychnine; C031503:phenylpiperazine; D010433:Pentylenetetrazole; D010634:Phenobarbital
keywords: 2-Thiohydantoin; Anticonvulsant; Epilepsy; Phenylpiperazine