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-PhCH2NHCH2–) 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 (EC50 = 2.0–14.0 μM, CC50 >100 μM) with the substituent groups such as Cl, Br, I, and Me specifically at the 3-position of the aromatic ring.

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