Studies on antiviral agents. IV. Synthesis and in vitro antiviral activity of new N-palmitoylkanamycin A derivatives.

During the initial stages of this program1-3), we discovered that 1-N-(higher-acyl)-3"-N-substituted kanamycin A derivatives exhibited the remarkable antiviral activity against not only herpes simplex virus type I Miyama (HSV-I) but also influenza virus A/PR8 (influenza virus). Among these analogs, 1-N-palmitoyl-3"-N-(trifluoroacetyl)kanamycin A dihydrochloride (12) was found to show both antiviral activity and low cytotoxicity. Also, 1-N-palmitoylkanamycin A trihydrochloride (3), which was unsubstituted at the N-3" position, exhibited this excellent antiviral activity. However, the cytotoxicity on Vero cells of 3 was stronger than that of 12. Based on these results, we have suggested that the introduction of higher-acyl group at the N-1 position of kanamycin A (1) was essential for emergence of the antiviral activity, and that the introduction of trifluoroacetyl group at the N-3"