title: 1-[(2-arylthiazol-4-yl)methyl]azoles as a new class of anticonvulsants: design, synthesis, in vivo screening, and in silico drug-like properties.
abstract: A series of novel thiazole incorporated (arylalkyl)azoles were synthesized and screened for their anticonvulsant properties using maximal electroshock and pentylenetetrazole models in mice. Among target compounds, 1-[(2-(4-chlorophenyl)thiazol-4-yl)methyl]-1H-imidazole (compound 4b), 1-[(2-phenylthiazol-4-yl)methyl]-1H-1,2,4-tria-zole (8a), and its 4-chlorophenyl analog (compound 8b) were able to display noticeable anticonvulsant activity in both pentylenetetrazole and maximal electroshock tests with percentage protection range of 33-100%. A computational study was carried out for prediction of pharmacokinetics properties and drug-likeness. The structure-activity relationship and in silico drug relevant properties (molecular weight, topological polar surface area, clog P, hydrogen bond donors, hydrogen bond acceptors, and log BB) confirmed that the compounds were within the range set by Lipinski's rule-of-five, and possessing favorable physicochemical properties for acting as CNS-drugs, making them potentially promising agents for epilepsy therapy.
authors.affiliation: Department of Toxicology and Pharmacology and Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.
authors.forename: Nematollah
authors.initials: N
authors.lastname: Ahangar
authors.forename: Adile
authors.initials: A
authors.lastname: Ayati
authors.forename: Eskandar
authors.initials: E
authors.lastname: Alipour
authors.forename: Arsalan
authors.initials: A
authors.lastname: Pashapour
authors.forename: Alireza
authors.initials: A
authors.lastname: Foroumadi
authors.forename: Saeed
authors.initials: S
authors.lastname: Emami
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D001393:Azoles / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D001812:Blood-Brain Barrier / Q000378:metabolism; D015195:Drug Design; D008297:Male; D051379:Mice; D012640:Seizures / Q000188:drug therapy
chemical_list: D000927:Anticonvulsants; D001393:Azoles