Synthesis, Biological Evaluation and Docking Study of New 1,2,4–Triazolo[4,3–b][1,2,4]Triazines and 1,2,4–Triazolo[4,3b][1,2,4,5] Tetrazines

摘要

Anovel series of 1,2,4–triazolo[4,3–b][1,2,4]triazines3–6and1,2,4–triazolo[1,2,4,5] tetrazines 8–12 weresynthesizedbyusingheterocyclizationof3–(pyridin–4yl)–4–amino–5–substitutedamino–1,2,4–triazole(2)and/or3–(pyridin–4yl)–4–amino–5–hydrazino–1,2,4–triazole(7) with α,β–bifunctional compounds such as chloromethyl diphenyl phosphonic acid phenacyl bromide, pyruvic acid, diethyloxalate, triethyl phosphite, triethyl orthoformte, fluorinated benzaldehydes, ethylchloroformate and carbon disulfide in different conditions. Moreover, compounds 3, 6, 8, 7, 9, 10, 11 and 12 displayed high inhibition against all bacteria tested in compared with the standard antibiotic Indomethacin. The newly synthesized compounds were evaluated for their in vivo anti–inflammatory activities and the results revealed that the compounds 7,8,10 and 12 have high % inhibition of edema as compared to standard drug (Indomethacin). Molecular docking studies were performed in order to investigate the plausible binding modes of synthesized compounds 8 and 10 into the active sites of enzyme COX–II.