Discovery, total synthesis, HRV 3C-protease inhibitory activity, and structure-activity relationships of 2-methoxystypandrone and its analogues

Bioorg Med Chem Lett. 2001 Dec 17;11(24):3143-6. doi: 10.1016/s0960-894x(01)00648-5.

Abstract

2-Methoxystypandrone, a naphthoquinone, was isolated from a Chinese herb Polygonum cuspidatum by bioassay guided fractionation using HRV 3C-protease assay. It showed an IC(50) value of 4.6 microM and is moderately selective. A new 10-step, total synthesis of 2-methoxystypandrone was accomplished in 45% overall yield using a Diels-Alder approach. Several analogues of this compound were prepared. Isolation, synthesis and HRV 3C-protease structure-activity relationships of these compounds have been described.

MeSH terms

  • 3C Viral Proteases
  • Cysteine Endopeptidases
  • Naphthoquinones / chemical synthesis*
  • Naphthoquinones / chemistry
  • Naphthoquinones / isolation & purification*
  • Protease Inhibitors / chemical synthesis*
  • Protease Inhibitors / chemistry
  • Protease Inhibitors / pharmacology*
  • Structure-Activity Relationship
  • Viral Proteins / antagonists & inhibitors*

Substances

  • 2-Methoxystypandrone
  • Naphthoquinones
  • Protease Inhibitors
  • Viral Proteins
  • Cysteine Endopeptidases
  • 3C Viral Proteases