Collect. Czech. Chem. Commun. 1987, 52, 3034-3041

Inhibitors of pancreatic and leukocyte elastase

Evžen Kasafíreka, Přemysl Fričb, Jan Slabýc and Petr Kocnab

a Research Institute for Pharmacy and Biochemistry, 130 60 Prague 3
b Laboratory of Gastroenterology, Charles University, 121 11 Prague 2
c Department of Medicine, Policlinic of Charles University, 121 11 Prague 2


The following alkylamides of ω-carboxyalkanoyldi- and tripeptides of the Ala-Pro or Ala-Ala-Pro sequence have been prepared: ethylamide-, propylamide-, and isobutylamide of 3-carboxypropionylalanyl-proline, ethylamide of 3-carboxypropionylalanyl-alanyl-proline and ethylamide-, propylamide, and isobutylamide of 4-carboxybutyrylalanyl-alanyl-proline. The inhibitors were synthesized by fragment condensation in solution or by gradual construction. The inhibition constants Ki were determined by means of pancreatic elastase (substrates - p-nitroanilides of 4-carboxybutyrylalanyl-alanyl-alanyl-alanine and 3-carboxypropionylalanyl-alanyl-alanyl-alanine) and leukocyte elastase (substrate - p-nitroanilide of 4-carboxybutyrylalanyl-alanyl-alanyl-valine). The strongest inhibitions (Ki) were recorded in ethylamide of 4-carboxybutyrylalanyl-alanyl-proline, 2.0 and 1.6 μmol l-1 for pancreatic elastase, and in propylamide of 4-carboxybutyrylalanyl-alanyl-proline, 0.4 mmol l-1 for leukocyte elastase.