2-Arylmethylaminomethyl-5,6-dihydroxychromone derivatives with selective anti-HCV activity.

Anti-HCV activity of aryl diketoacid (ADK) has been characterized by its two pharmacophoric elements, α,β-diketo acid moiety and substituted aryl ring. In this study, as a part of our ongoing efforts to discover a novel anti-HCV compound mimicking the ADK scaffold, we designed 2-arylmethylaminomethyl-5,6-dihydroxychromone derivatives of which the dihydroxychromone moiety as well as the arylmethylaminomethyl substituent (R-PhCH(2)NHCH(2)-) were anticipated in exact match with the pharmacophore model of the ADK. The dihydroxychromone derivatives (3a-3u), thus prepared, showed biological activity in a substituent-dependent fashion, thereby leading to selective anti-HCV effect (EC(50)=2.0-14.0 μM, CC(50) >100 μM) with the substituent groups such as Cl, Br, I, and Me specifically at the 3-position of the aromatic ring.