New Phenylglycinamide Derivatives with Hybrid Structure as Candidates for New Broad-Spectrum Anticonvulsants.

ABSTRACT: In the present study, a focused combinatorial chemistry approach was applied to merge structural fragments of well-known TRPV1 antagonists with a potent anticonvulsant lead compound, KA-104, that was previously discovered by our group. Consequently, a series of 22 original compounds has been designed, synthesized, and characterized in the in vivo and in vitro assays. The obtained compounds showed robust in vivo antiseizure activity in the maximal electroshock (MES) test and in the 6 Hz seizure model (using both 32 and 44 mA current intensities). The most potent compounds 53 and 60 displayed the following pharmacological profile: ED₅₀ = 89.7 mg/kg (MES), ED₅₀ = 29.9 mg/kg (6 Hz, 32 mA), ED₅₀ = 68.0 mg/kg (6 Hz, 44 mA), and ED₅₀

SUBMITTER: Jakubiec M 

PROVIDER: S-EPMC9221546 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature