The discovery of a potent, intracellular, orally bioavailable, long duration inhibitor of human neutrophil elastase--GW311616A a development candidate

Bioorg Med Chem Lett. 2001 Apr 9;11(7):895-8. doi: 10.1016/s0960-894x(01)00078-6.

Abstract

The discovery of a potent intracellular inhibitor of human neutrophil elastase which is orally active and has a long duration of action is described. The pharmacodynamic and pharmacokinetic properties of a trans-lactam development candidate, GW311616A, are described.

MeSH terms

  • Administration, Oral
  • Animals
  • Bacteria / drug effects
  • Bacterial Infections / drug therapy
  • Biological Availability
  • Cricetinae
  • Crystallization
  • Dogs
  • Drug Stability
  • Lactams / pharmacokinetics*
  • Lactams / pharmacology*
  • Leukocyte Elastase / antagonists & inhibitors
  • Leukocyte Elastase / metabolism
  • Metabolic Clearance Rate / physiology
  • Pancreatic Elastase / chemistry
  • Piperidines / chemistry*
  • Piperidines / pharmacokinetics
  • Piperidines / pharmacology*
  • Rats
  • Serine Endopeptidases / drug effects
  • Serine Endopeptidases / metabolism
  • Serpins / chemistry*
  • Serpins / pharmacokinetics
  • Serpins / pharmacology*

Substances

  • GW 311616
  • Lactams
  • Piperidines
  • Serpins
  • Serine Endopeptidases
  • Pancreatic Elastase
  • Leukocyte Elastase

Associated data

  • PDB/1HV7