New Route to the Synthesis of Benzamide-Based 5-Aminopyrazoles and Their Fused Heterocycles Showing Remarkable Antiavian Influenza Virus Activity.

ABSTRACT

This study describes a new route to the synthesis of novel benzamide-based 5-aminopyrazoles and their corresponding pyrazolo[1,5-a]pyrimidine and pyrazolo[5,1-c][1,2,4]triazine derivatives. Benzamide-based 5-aminopyrazoles were prepared through a reaction of benzoyl isothiocyanate with malononitrile in KOH-EtOH followed by alkylation with alkyl halides and then a reaction with hydrazine. In an attempt to react benzoyl isothiocyanate with ethyl cyanoacetate in KOH-EtOH followed by alkylation with methyl iodide at room temperature and then a reaction with hydrazine has resulted in the formation of 3-ethoxy-5-phenyl-1H-1,2,4-triazole. The structures of the new compounds were characterized by mass spectroscopy, 1H nuclear magnetic resonance (1H NMR) spectroscopy, infrared spectroscopy (IR), and X-ray analysis. The new compounds were tested in vitro for their anti-influenza A virus (subtype H5N1) activity. Among the synthesized compounds, eight compounds 3b, 4, 10b, 10c, 12a, 19, 21a, and 21b were found to possess significant antiviral activities against bird flu influenza (H5N1) with viral reduction in the range of 85-65%.