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1‐[(2‐Arylthiazol‐4‐yl)methyl]azoles as a New Class of Anticonvulsants: Design, Synthesis, In vivo Screening, and In silico Drug‐like Properties
Author(s) -
Ahangar Nematollah,
Ayati Adile,
Alipour Eskandar,
Pashapour Arsalan,
Foroumadi Alireza,
Emami Saeed
Publication year - 2011
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/j.1747-0285.2011.01211.x
Subject(s) - polar surface area , anticonvulsant , chemistry , in silico , thiazole , lipinski's rule of five , hydrogen bond , in vivo , stereochemistry , pharmacokinetics , drug , pharmacology , combinatorial chemistry , molecule , epilepsy , organic chemistry , medicine , biochemistry , biology , microbiology and biotechnology , psychiatry , gene
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]‐1 H ‐imidazole (compound 4b ), 1‐[(2‐phenylthiazol‐4‐yl)methyl]‐1 H ‐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, c log 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.