One-Pot Synthesis of Indole-3-acetic Acid Derivatives through the Cascade Tsuji–Trost Reaction and Heck Coupling

A practical palladium-mediated cascade Tsuji–Trost reaction/Heck coupling of N-Ts <i>o</i>-bromoanilines with 4-acetoxy-2-butenonic acid derivatives using a Pd­(OAc)₂/P­(<i>o</i>-tol)₃/DIPEA system is described for a straightforward synthesis of indole-3-acetic acid derivatives. This methodology was successfully applied to synthesize various substituted indole/azaindole-3-acetic acid derivatives and Almotriptan, which is a drug for the acute treatment of migraines. Moreover, a plausible cyclization mechanism has been proposed

Discovery of Imidazo[1,2-α][1,8]naphthyridine Derivatives as Potential HCV Entry Inhibitor

RO8191 represents a newly discovered small-molecule IFN-like agent that displays potent anti-HCV activity. With it as lead, a series of compounds bearing an imidazo­[1,2-α]­[1,8]­naphthyridine core and an amide bond-linked side chain were designed and synthesized. These compounds were evaluated on HCV cell culture system (HCVcc-hRluc-JFH1), and some of them exhibited remarkable anti-HCV activity (EC₅₀ = 0.017–0.159 μM) and low toxicity (CC₅₀ > 25 μM). Moreover, it was revealed that these newly identified anti-HCV agents exert their antiviral effect through a distinct mechanism of action from that of RO8191 by targeting the viral entry process. Thus, our study provides a starting point for the development of potential HCV entry inhibitor