Synthesis and anti-influenza virus activity of novel pyrimidine derivatives

Abstract

Efficient synthetic routes of 2-amino-4-(ω-hydroxyalkylamino)pyrimidine derivatives were investigated in relation to the anti-influenza virus activity of these compounds. The derivatives in which cyclobutyl and cyclopentyl groups were introduced to the β-position of the aminoalkyl group (especially the cyclobutyl group substituted by a phenylalkyl group at the 3′-position) resulted in improved antiviral potency: i.e. an average 50% effective concentration for inhibition of plaque formation (EC 50, μM) of 0.1–0.01 μM for both types A and B influenza virus. The antiviral efficacies were in the order of amino group>hydroxyiminomethyl group>halogen substitution at the 5-position, and chlorine or methoxy group>hydrogen at the 6-position of the pyrimidine ring. The antiviral indices of these compounds were 2–6 with respect to the 50% inhibitory concentration for cell proliferation (IC 50, μM) for growing cells, but >500 to >10 4 with respect to the IC 50 for stationary cells, indicating that these compounds may be efficacious for the topical treatment of influenza virus infection.