Inhibition of human leukocyte elastase by N-substituted tripeptide trifluoromethyl ketones

Several tripeptide trifluoromethyl ketones containing non-naturally occurring N-substituted glycine residues at the P2-position are effective human leukocyte elastase (HLE) inhibitors in vitro and possess IC50 values in the submicromolar range. Deletion of the amino acid at the P3-subsite region affords inactive compounds. The trifluoromethyl ketone derivative of valine is the preferred residue at the P1-position; whereas, the corresponding glycine or alpha, alpha-dimethyl glycine analogs result in inactive compounds.