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

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-1 H -1,2,4-triazole. The structures of the new compounds were characterized by mass spectroscopy, 1 H nuclear magnetic resonance ( 1 H 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%.