Synthesis, Characterization, Docking and Biological Evaluation of Tetra Hydro Imidazo [1, 2-a] Pyrazine Derivatives

Abstract

Novel Tetra hydro imidazo[1, 2-a] pyrazine derivatives have been synthesized by Treatment of pyrazine-2carboxylic acid with thionyl chloride in methanol yielded methyl pyrazine-2-carboxylate. This up on treatment with alcoholic ammonia gave pyrazinamide, further it was undergone Hoffman's degradation, gave 2-amino pyrazine after that it was refluxed for 26 hrs with chloro acetaldehyde, sodium bicarbonate gave imidazo[1, 2-a] pyrazine and hydrogen gas was passed on it in the presence of palladium on carbon yielded tetra hydro imidazo[1, 2-a] pyrazine, which was treated with different substituent's to get the novel derivatives. Synthesized compounds were identified and characterized by Melting point, TLC, FT-IR, 1H and 13C NMR, MASS and percent purity done by HPLC. Based on characterization and percent purity novel derivatives were subjected for molecular docking, QSAR studies and pharmacological evaluation. Selected compounds were docked on Anti oxidant activity using “Thioredoxin peroxidase B” as a target site. QSAR parameters like partition coefficient was studied and showed polar surface area below 140 A0 and passed ADME parameters. Analysis of docking and QSAR studies suggested that remarkable inhibitory activity was exhibited by the derivatives. Hydrogen bond interactions were mapped to confirm their potencies. They were evaluated for In-Vitro Anti-oxidant activity by DPPH method and In-Vitro Anti-diabetic activity by alpha-amylase inhibition assay by DNSA method. Results suggested that electron withdrawing groups like nitro, bromo having compounds shown potent activity. Rest of compounds showed mild to moderate activity.