The present invention provides Beta-hairpin peptidomimetics which are useful as inhibitors of protease enzymes. In particular, the invention provides backbone cyclized peptidic compound, built up from 13 amino acid residues, of the general formula cyclo(Xaa1 Xaa2 Thr3 Xaa4 Ser5 Xaa6 Xaa7 Xaa8 Xaa9 Xaa10 Xaa11 Xaa12 Xaa13) (I), and pharmaceutically acceptable salts thereof, wherein Xaa1 is OctGly； Arg； hArg； or Glu(Phenethyl)； Xaa2 is Glu； Nle； hTyr； or Val； Xaa4 is Ala； or AllylGly； Xaa6 is Ile； Xaa7 is Pro； Xaa8 is Pro； Xaa9 is Gln； or Tyr； Xaa10 is Lys； Xaa11 is hLeu； Ser； Thr； Asn； Tyr； hGln； or His； Xaa12 is DPro； and Xaa13 is Pro； with the proviso that if Xaa1 is OctGly, then Xaa2 is Glu； or Nle； Xaa4 is Ala； Xaa6 is Ile； Xaa10 is Lys； Xaa11 is Ser； Thr； or Asn； Xaa13 is Pro； and with the further proviso that if Xaa11 is Tyr； or His, then Xaa1 is Arg； hArg or Glu(Phenethyl). The compounds of the invention have elastase inhibitory properties, especially against human neutrophil elastase, and can be used for preventing infections or diseases related to such infections in healthy individuals or for slowing infections in infected patients. The compounds of the invention can further be used where cancer, or immunological diseases, or pulmonary diseases, or cardiovascular diseases, or neurodegenerative diseases, or inflammation, or diseases related to inflammation, are mediated or resulting from elastase activity. These peptidomimetics can be manufactured by a process which is based on a mixed solid and solution phase synthetic strategy.
