Synthesis, Characterization, and Biological Evaluation of Some Novel Quinoxaline Derivatives as Antiviral Agents

Ethyl (6,7‐dimethyl‐2‐oxo‐3,4‐dihydroquinoxalin‐3‐yl)acetate and ethyl (6‐methyl‐2‐oxo‐3,4‐dihydroquinoxalin‐3‐yl)acetate (1a,b), 3‐methylquinoxalin‐2(1H)‐one (4) and 1,4‐dihydroquinoxaline‐2,3‐dione (11) were the starting precursors for nine novel quinoxaline compounds, 3a, 6, 10, 13, 15, 16, 17, 18, and 20, via adopting different nucleophilic reactions. The synthesized compounds were tested for their antiviral activity against HCV, HBV, HSV‐1, and HCMV. Concomitantly, their safety profile was investigated as well as their selectivity against the viral strains. The Virology Unit at the University of Alabama recorded that two compounds, i.e., 1a and 20, exhibited highly potent activity against HCMV with lower IC50 values (<0.05 μM) compared to ganciclovir (IC50 = 0.59 μM). Compounds 1a and 20 also exhibited low cytotoxicity together with a high selectivity index. A four‐step preparation method comprising hydrazinolysis, reaction with triethylorthoformate, nucleophilic attack of 2‐aminopyridine on hydrazonoderivatives, then intramolecular cyclization was applied to transform compound 1a to 20. The quinoxaline derivative 20 exhibited higher activity against human cytomegalovirus (EC50 < 0.05 µM) compared to ganciclovir as the reference standard (EC50 = 0.59 µM).
Source: Archiv der Pharmazie - Category: Drugs & Pharmacology Authors: Tags: Full Paper Source Type: research