Design, Synthesis and Anticonvulsant Activity of Cinnamoyl Derivatives of 3,4,6,7,8,9-hexahydrodibenzo[]furan-1-(2H)-one Oxime.

Background: Epilepsy continues to be a significant global health problem and the search for new drugs for its treatment remains an urgent task. 5-HT2 and GABAA-receptors are among promising biotargets for the search for new anticonvulsants.

Methods: New potential 5-HT2 and GABAA ligands in the series of substituted cinnamoyl derivatives of 3,4,6,7,8,9-hexahydrodibenzo[b,d]furan-1-(2H)-one oxime were designed using pharmacophore model and molecular docking analysis.

Design, Synthesis and Pharmacological Activity of New Pyrrolo[1,2-A] Pyrazine Translocator Protein (TSPO) Ligands.

Background: Translocator protein 18 kDa (TSPO) is a promising target for the creation of effective and safe neuropsychotropic drugs. The ligands of TSPO exhibit anxiolytic, antidepressant, neuroprotective and other activities without the side effects of benzodiazepines.

Methods: New TSPO ligands in the series of N,1-diphenylpyrrolo[1,2-a]pyrazine-3-carboxamides derivatives were designed using calculated pharmacophore model and molecular docking analysis.

The New Dipeptide TSPO Ligands: Design, Synthesis and Structure-Anxiolytic Activity Relationship.

The translocator protein (TSPO, 18 kDa) plays an important role in the synthesis of neurosteroids by promoting the transport of cholesterol from the outer to the inner mitochondrial membrane, which is the rate-limiting step in neurosteroidogenesis. Stimulation of TSPO by appropriate ligands increases the level of neurosteroids. The present study describes the design, synthesis and investigation of anxiolytic-like effects of a series of -acyl-tryptophanyl-containing dipeptides.

A Novel Dipeptide Ligand of TSPO.

On the basis of the first dipeptide ligand of TSPO, N-carbobenzoxy-L-tryptophanyl-L-isoleucine amide (GD-23), which was obtained by us earlier, we synthesized a new dipeptide, N-phenylpropionyl-L-tryptophanyl-L-leucine amide (GD-102). GD-102 exhibited anxiolytic activity in the open field test in BALB/c mice and in the elevated plus maze test in ICR mice. The minimum effective dose of GD-102 was one order of magnitude lower than that of GD-23.