A novel orally active inhibitor of HLE

Eur J Med Chem. 2003 Apr;38(4):421-5. doi: 10.1016/s0223-5234(03)00046-1.

Abstract

Human leukocyte elastase (HLE) is a serine proteinase, capable of degrading a variety of structural matrix proteins. SSR69071 2-[(4-isopropyl-6-methoxy-1,1-dioxido-3-oxo-1,2-benzisothiazol-2(3H)-yl)methoxy]-9-(2-piperidin-1-ylethoxy)-4H-pyrido[1,2-a]pyrimidin-4-one was selected as a novel orally active HLE inhibitor for treatment of chronic obstructive pulmonary diseases, asthma, emphysema, cystic fibrosis and several inflammatory diseases (WO 01/44245 A1) (J. Pharm. Exp. Ther., submitted for publication).

Publication types

  • Comparative Study

MeSH terms

  • Administration, Oral
  • Animals
  • Asthma / chemically induced
  • Asthma / drug therapy
  • Asthma / pathology
  • Cyclic S-Oxides / chemistry
  • Cyclic S-Oxides / metabolism
  • Cyclic S-Oxides / pharmacology*
  • Cystic Fibrosis / chemically induced
  • Cystic Fibrosis / drug therapy
  • Cystic Fibrosis / pathology
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / metabolism
  • Enzyme Inhibitors / pharmacology*
  • Hemorrhage / chemically induced
  • Hemorrhage / drug therapy
  • Hemorrhage / pathology
  • Humans
  • Inflammation / chemically induced
  • Inflammation / drug therapy
  • Inflammation / pathology
  • Leukocyte Elastase / administration & dosage
  • Leukocyte Elastase / antagonists & inhibitors*
  • Leukocyte Elastase / metabolism
  • Lung Diseases, Obstructive / chemically induced
  • Lung Diseases, Obstructive / drug therapy
  • Lung Diseases, Obstructive / pathology
  • Mice
  • Models, Chemical
  • Pulmonary Emphysema / chemically induced
  • Pulmonary Emphysema / drug therapy
  • Pulmonary Emphysema / pathology
  • Thiazoles / chemistry
  • Thiazoles / metabolism
  • Thiazoles / pharmacology*

Substances

  • Cyclic S-Oxides
  • Enzyme Inhibitors
  • SSR 69071
  • Thiazoles
  • Leukocyte Elastase