Synthesis and biological evaluation of novel urea and thiourea derivatives of valacyclovir

Abstract

A series of novel urea and thiourea derivatives of valacyclovir were efficiently synthesized in high yields and evaluated their antiviral activity. 2-((6-Amino-4-oxo-4,5-dihydro-1H-imidazo[4,5-c]pyridin-1-yl)methoxy)ethyl-2-amino-3-ethylbutanoate (valacyclovir) 1 is reacted with various aromatic isocyanates/thiocyanates 2 in the presence of N, N- dimethyl piperazine as a base in THF: pyridine (4:1) to obtain valacyclovir urea/thiourea derivatives 3(a-j). The structures of the title compounds 3(a-j) were confirmed by IR, NMR (1H, 13C), mass spectral and elemental analysis. The newly synthesized compounds were screened for their antiviral activity against Tobacco mosaic virus (TMV) and antioxidant activity was evaluated by DPPH, SOD and GST methods. The title compounds exhibited potent antiviral and good antioxidant activities.

Keywords

• isocyanate
• isothiocyanate
• N,N-dimethyl piperazine
• tobacco mosaic virus
• antiviral
• anti-oxidant activity