Design and Synthesis of 6-substituted amino-4-oxa-1-azabicyclo[3,2,0]heptan-7-one Derivatives as Cysteine Proteases Inhibitors

Bioorg Med Chem Lett. 2002 Dec 2;12(23):3413-5. doi: 10.1016/s0960-894x(02)00765-5.

Abstract

A series of 6-substituted amino-4-oxa-1-azabicyclo[3,2,0]heptan-7-one compounds was designed and synthesized as a new class of inhibitors for cysteine proteases cathepsins B, L, K, and S. One compound (5S,6S)-6-(N-benzyloxycarbonyl-L-phenylalanyl) amino-4-oxa-1-azabicyclo[3,2,0]heptan-7-one showed excellent cathepsin L and K inhibition activity with IC(50) at a low nanomolar range.

MeSH terms

  • Cathepsins / antagonists & inhibitors
  • Cysteine Proteinase Inhibitors / chemical synthesis*
  • Cysteine Proteinase Inhibitors / pharmacology*
  • Drug Design
  • Inhibitory Concentration 50
  • Lactams / chemistry*
  • Lactams / pharmacology*
  • Models, Molecular
  • Papain / antagonists & inhibitors
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Cysteine Proteinase Inhibitors
  • Lactams
  • 4-oxa-1-azabicyclo(3.2.0)heptan-7-one
  • Cathepsins
  • Papain