Development of Novel Alaninamide Derivatives with Anticonvulsant Activity and Favorable Safety Profiles in Animal Models.

ABSTRACT: In our current study, we developed a focused series of original ((benzyloxy)benzyl)propanamide derivatives that demonstrated potent activity across in vivo mouse seizure models, specifically, maximal electroshock (MES) and 6 Hz (32 mA) seizures. Among these derivatives, compound 5 emerged as a lead molecule, exhibiting robust protection following intraperitoneal (i.p.) injection, as follows: ED₅₀ = 48.0 mg/kg in the MES test, ED₅₀ = 45.2 mg/kg in the 6 Hz (32 mA) test, and ED₅₀ = 201.3 mg/kg in the 6 Hz (44 mA) model. Additionally, compound 5 displayed low potential for inducing motor impairment in the rotarod test (TD₅₀ > 300 mg/kg), indicating a potentially favorable therapeutic window. In vitro toxicity assays further supported i

SUBMITTER: Abram M 

PROVIDER: S-EPMC11432405 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature