Des-amino basic pancreatic trypsin inhibitor analogues - useful as protease inhibitors for treating inflammations, shock, blood clotting, atherosclerosis etc.

摘要

New desamino derivs. (I) of basic pancreatic trypsin inhibitor (BPTI) are derived from opt. desamidated BPTI analogues (II) in which (a) all COOH gps. are substd. by amino acid or peptide residues and/or (b) the Tyr10 and/or Tyr21 residues contain NO2 and/or NH2 gps. in the ortho posn. to the phenolic OH gp. (I) are prepd. by reacting (II) with a cpd. capable of releasing nitrosyl ions (pref. alkali metal nitrites) at -20 to +30 degrees C and pH 1-7 in an aq. or aq.-organic medium, opt. in the presence of a nucleophilic reagent. (I) are protease inhibitors with esp. high activity against pancreatic and granulocytic elastases. They can be used to treat disorders associated with enzymatic dysfunction, e.g. inflammations (pancreatitis, arthritis, etc.) shock, blook clotting disorders and atherosclerosis; and have higher activity than BPTI against kaolin- and aerosol-induced inflammations. They can also be used as intermediates for azo-BPTI derivs.