title: Design and synthesis of novel stiripentol analogues as potential anticonvulsants.
abstract: A series of stiripentol (STP) analogues namely, 2-[(1E)-1-(1,3-benzodioxol-5-yl)-4,4-dimethylpent-1-en-3-ylidene]-N-(aryl/H)hydrazinecarboxamides 7a-h, (±)-(5RS)-N-(aryl/H)-(1,3-benzodioxol-5-yl)-3-tert-butyl-4,5-dihydro-1H-pyrazole-1-carboxamides (±)-8a-h, and (±)-[(5RS)-(1,3-benzodioxol-5-yl)-3-tert-butyl-4,5-dihydro-1H-pyrazol-1-yl](aryl)methanones (±)-13a-f was synthesized by adopting appropriate synthetic routes and was pharmacologically evaluated in the preliminary anticonvulsant screens. The selected bioactive new chemical entities were subjected to ED(50) determination and neurotoxicity evaluation. The most active congeners are 7h in MES screen and (±)-13b in scPTZ screen which displayed ED(50) values of 87 and 110 mg/kg, respectively, as compared to that of STP (ED(50) = 277.7 and 115 mg/kg in MES and scPTZ, respectively).
authors: Medicinal and Pharmaceutical Chemistry Department (Medicinal Chemistry group), Pharmaceutical and Drug Industries Research Division, National Research Centre, 12622 Dokki, Giza, Egypt. mnaboulenein@yahoo.com
authors: Mohamed N
authors: MN
authors: Aboul-Enein
authors: Aida A
authors: AA
authors: El-Azzouny
authors: Mohamed I
authors: MI
authors: Attia
authors: Yousreya A
authors: YA
authors: Maklad
authors: Kamilia M
authors: KM
authors: Amin
authors: Mohamed
authors: M
authors: Abdel-Rehim
authors: Mohammed F
authors: MF
authors: El-Behairy
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D004148:Dioxolanes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D015195:Drug Design; D018737:Hand Strength / Q000502:physiology; D008297:Male; D051379:Mice; D012640:Seizures / Q000188:drug therapy; D013237:Stereoisomerism; D018675:Toxicity Tests
chemical_list: D000927:Anticonvulsants; D004148:Dioxolanes; C021092:stiripentol