5-Carba-pterocarpens: A New Scaffold With anti-HCV Activity

Eur J Med Chem. 2016 Apr 13;112:33-38. doi: 10.1016/j.ejmech.2016.02.010. Epub 2016 Feb 6.

Abstract

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.

Keywords: BBr(3) mediated demethylation-cyclization; Carba-pterocarpens; Hepatitis C virus inhibitors; Microwave irradiation; Palladium catalyzed arylation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anisoles / chemical synthesis
  • Anisoles / chemistry
  • Anisoles / pharmacology
  • Antiviral Agents / chemical synthesis
  • Antiviral Agents / chemistry*
  • Antiviral Agents / pharmacology*
  • Catalysis
  • Cell Line
  • Guanidines / chemical synthesis
  • Guanidines / chemistry*
  • Guanidines / pharmacology*
  • Hepacivirus / drug effects*
  • Hepacivirus / genetics
  • Hepatitis C / drug therapy
  • Hepatitis C / virology
  • Humans
  • Palladium / chemistry
  • Replicon / drug effects
  • Tetralones / chemical synthesis
  • Tetralones / chemistry
  • Tetralones / pharmacology

Substances

  • Anisoles
  • Antiviral Agents
  • Guanidines
  • Tetralones
  • dodine
  • Palladium