title: Synthesis and Anticonvulsant Activity of Substituted-1,3-diazaspiro[4.5]decan-4-ones.
abstract: A series of novel spiroimidazolidinone derivatives 6a-d and 8a-x were synthesized and biologically evaluated for their anticonvulsant activity in the maximal electroshock seizure (MES) assay and the subcutaneous pentylenetetrazole (scPTZ) screening test. Compound 8w was the most active derivative in the scPTZ screening test with an ED50 value by about 5- and 83.6-fold lower than those of phenobarbital and ethosuximide as reference drugs, respectively. Most of the tested compounds exhibited moderate to weak activity in the MES screen test, except for 8a which displayed 100% protection at 0.09 mmol/kg. Moreover, all the test compounds did not show any minimal motor impairment in the neurotoxicity test.
authors.affiliation: Pharmaceutical and Medicinal Chemistry Department, Medicinal Chemistry Group, Pharmaceutical and Drug Industries Research Division, National Research Centre (ID: 60014618), Dokki, Giza, Egypt.
authors.forename: Mohamed Nabil
authors.initials: MN
authors.lastname: Aboul-Enein
authors.affiliation: Pharmaceutical and Medicinal Chemistry Department, Medicinal Chemistry Group, Pharmaceutical and Drug Industries Research Division, National Research Centre (ID: 60014618), Dokki, Giza, Egypt.
authors.forename: Aida Abdel Sattar
authors.initials: AA
authors.lastname: El-Azzouny
authors.affiliation: Pharmaceutical and Medicinal Chemistry Department, Medicinal Chemistry Group, Pharmaceutical and Drug Industries Research Division, National Research Centre (ID: 60014618), Dokki, Giza, Egypt.
authors.forename: Ola Ahmed
authors.initials: OA
authors.lastname: Saleh
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
authors.forename: Kamilia Mahmoud
authors.initials: KM
authors.lastname: Amin
authors.affiliation: Pharmaceutical and Medicinal Chemistry Department, Pharmacology Group, Pharmaceutical and Drug Industries Research Division, National Research Centre (ID: 60014618), Dokki, Giza, Egypt.
authors.forename: Yousreya Ali
authors.initials: YA
authors.lastname: Maklad
authors.affiliation: Pharmaceutical and Medicinal Chemistry Department, Medicinal Chemistry Group, Pharmaceutical and Drug Industries Research Division, National Research Centre (ID: 60014618), Dokki, Giza, Egypt.
authors.forename: Rasha Mohamed
authors.initials: RM
authors.lastname: Hassan
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D001522:Behavior, Animal; D001921:Brain / Q000187:drug effects / Q000503:physiopathology; D004195:Disease Models, Animal; D015195:Drug Design; D004597:Electroshock; D007093:Imidazoles / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D008297:Male; D051379:Mice; D015394:Molecular Structure; D009043:Motor Activity / Q000187:drug effects; D010433:Pentylenetetrazole; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D013329:Structure-Activity Relationship
chemical_list: D000927:Anticonvulsants; D007093:Imidazoles; D010433:Pentylenetetrazole
keywords: 1,3-Diazaspiro[4.5]decan-4-ones; Anticonvulsants; Epilepsy