Design, Synthesis and Biological Activity of New Amides Derived From 3-Benzhydryl and 3-Sec-butyl-2,5-dioxo-pyrrolidin-1-yl-acetic Acid.

Design, Synthesis and Biological Activity of New Amides Derived From 3-Benzhydryl and 3-Sec-butyl-2,5-dioxo-pyrrolidin-1-yl-acetic Acid. ChemMedChem. 2021 Feb 04;: Authors: Góra M, Czopek A, Rapacz A, Giza A, Koczurkiewicz-Adamczyk P, Pękala E, Obniska J, Kamiński K Abstract The aim of studies was to design and synthesize two new series of pyrrolidine-2,5-dione-acetamides with benzhydryl or sec-butyl group at position-3 as potential anticonvulsants. Their anticonvulsant activity was evaluated in standard animal models of epilepsy: the maximal electroshock (MES), the 6 Hz, and the subcutaneous pentylenetetrazole (scPTZ) tests. The in vivo studies revealed the most potent anticonvulsant activity for 15 (3-(sec-butyl)-1-(2-(4-(3-trifluoromethylphenyl)piperazin-1-yl)-2-oxoethyl)pyrrolidine-2,5-dione), with ED50 values of 80.38 mg/kg (MES) and 108.80 mg/kg (6 Hz). The plausible mechanism of action was assessed in the in vitro binding assays, in which 15 interacted effectively with the voltage-gated sodium (site 2) and L-type calcium channels at the concentration of 100 μM. Subsequently, the antinociceptive activity of compounds 7 and 15 was observed in the hot plate test of acute pain. Moreover, compound 7, 11 and 15 demonstrated analgesic effect in the formalin test of tonic pain. Additionally, for the most effective compounds (7, 11 and 15) their hepatotoxic properties in HepG2 cells were also investigated. PMID: 33539029 [P...
Source: ChemMedChem - Category: Chemistry Authors: Tags: ChemMedChem Source Type: research