Synthesis, Molecular Docking and In Vitro Screening of Some Newly Synthesized Triazolopyridine, Pyridotriazine and Pyridine–Pyrazole Hybrid Derivatives

Abstract

A series of novel pyridine and fused pyridine derivatives have been prepared starting from 6-(3,4-dimethylphenyl)-2-hydrazinyl-4-(thiophen-2-yl)-pyridine-3-carbonitrile <b>1</b> which on treatment with appropriate formic acid, acetic acid/ acetic anhydride, benzoyl chloride and/or carbon disulfide afforded the corresponding triazolopyridine derivatives <b>2</b>⁻<b>5</b>. Also, treatment of hydrazide <b>1</b> with diethyloxalate, chloroacetyl chloride, chloroacetic acid and/or 1,2-dichloroethane yielded the corresponding pyridotriazine derivatives <b>7</b>⁻<b>10</b>. Further transformation of compound <b>1</b> with a different active methylene group, namely acetyl acetone, diethylmalonate, ethyl cyanoacetate, ethyl benzoylacetate and/or ethyl acetoacetate, produced the pyridine⁻pyrazole hybrid derivatives <b>11</b>⁻<b>15</b>. These newly synthesized compounds (<b>1</b>⁻<b>15</b>) were subjected to in silico molecular docking screenings towards GlcN-6-P synthase as the target protein. The results revealed moderate to good binding energies of the ligands on the target protein. All the newly prepared products exhibited antimicrobial and antioxidant activity.