RESUMEN

The synthesis of a series of 5-carba-pterocarpens derivatives involving the cyclization of α-aryl-α-tetralones is described. Several compounds demonstrated potent activity and selectivity in vitro against HCV replicon reporter cells. The best profile in Huh7/Rep-Feo1b replicon reporter cells was observed with 2h (EC50 = 5.5 µM/SI = 20), while 2e was the most active in Huh7.5-FGR-JC1-Rluc2A replicon reporter cells (EC50 = 1.5 µM/SI = 70). Hydroxy groups at A- and D-rings are essential for anti-HCV activity, and substitutions in the A-ring at positions 3 and 4 resulted in enhanced activity of the compounds.

Asunto(s)

Antivirales/química , Antivirales/farmacología , Guanidinas/química , Guanidinas/farmacología , Hepacivirus/efectos de los fármacos , Anisoles/síntesis química , Anisoles/química , Anisoles/farmacología , Antivirales/síntesis química , Catálisis , Línea Celular , Guanidinas/síntesis química , Hepacivirus/genética , Hepatitis C/tratamiento farmacológico , Hepatitis C/virología , Humanos , Paladio/química , Replicón/efectos de los fármacos , Tetralonas/síntesis química , Tetralonas/química , Tetralonas/farmacología