Abstract：
:A novel series of carbamoyl derivatives of alkylimidazole has been designed and their anticonvulsant activity was comparatively evaluated in the mice- and rats-maximal-electroshock (MES), subcutaneous-metrazol (scMet) seizure tests and the mice-6Hz psychomotor (6Hz) models. The ten new designed molecules contain in their chemical structure imidazole, alkyl side-chain and carbamate as three potential active moieties. In spite of the close structural features of the carbamoyl imidazole derivatives only compounds 7, 8, 13 and 16 were active at the MES test with ED50 values ranging from 12 to 20mg/kg coupled with high protective index (PI=TD50/ED50) values of 4.1-7.3 after ip administration to rats. A similar phenomenon was observed in mice where compounds 7, 8, 9, 12 had MES-ED50 values of 14-26mg/kg. Compounds 7 and 13 also demonstrated anticonvulsant activity in the 6Hz model with ED50 values of 32 and 44mg/kg, respectively. As the most active entities, compounds 7, 8 followed by 13 and 16, thus offer an optimal efficacy-safety profile and consequently, might be promising candidates for development as new antiepileptics.
journal_name
Bioorg Med Chemjournal_title
Bioorganic & medicinal chemistryauthors
Mawasi H,Bibi D,Bialer Mdoi
10.1016/j.bmc.2016.07.018subject
Has Abstractpub_date
2016-09-15 00:00:00pages
4246-4253issue
18eissn
0968-0896issn
1464-3391pii
S0968-0896(16)30522-3journal_volume
24pub_type
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