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

Abstract

Series of novel urea and thiourea derivatives of valaciclovir were efficiently synthesized in high yields and their antiviral activity was evaluated. (S)-2-[(2-amino-6-oxo-6,9-dihydro-3H-purin-9-yl)methoxy]ethyl 2-amino-3-methylbutanoate (valaciclovir) (1) was reacted with various aromatic isocyanates/ thiocyanates 2a-j in the presence of N,N'-dimethyl piperazine as a base in THF:pyridine (4:1) to obtain the valaciclovir urea/thiourea derivatives 3a-j. The structures of the title compounds (3a-j) were confirmed by their IR, NMR (1H and 13C) mass spectral data and elemental analysis. The newly synthesized compounds were screened for their antiviral activity against Tobacco mosaic virus (TMV) and antioxidant activity was evaluated by the 1,1-diphenyl- -2-picrylhydrazyl radical (DPPH) and superoxide dismutase (SOD) scavenging methods. The title compounds exhibited potent antiviral and good antioxidant activities. © 2014 Copyright SCS.