Substituted isatoic anhydrides: selective inactivators of trypsin-like serine proteases.
Derivatives of isatoic anhydride were prepared and tested as inhibitors of serine proteases. A number of isatoic anhydrides with positively charged substituents irreversibly inactivated several trypsin-like enzymes and preferentially inactivated trypsin over chymotrypsin. Further selectivity was obtained by introduction of an aromatic group on the N-1 position of isatoic anhydride. 7-(Aminomethyl)-1-benzylisatoic anhydride was prepared and was a selective inactivator of thrombin; thus it is possible to prepare derivatives of isatoic anhydride that are highly enzyme selective without attaching peptide recognition structures.
D000925:Anticoagulants / Q000494:pharmacology; D004355:Drug Stability; D010450:Endopeptidases; D006801:Humans; D007700:Kinetics; D010078:Oxazines / Q000138:chemical synthesis / Q000494:pharmacology*; D011480:Protease Inhibitors; D012697:Serine Endopeptidases; D013329:Structure-Activity Relationship; D014361:Trypsin Inhibitors / Q000494:pharmacology
D000925:Anticoagulants; D010078:Oxazines; D011480:Protease Inhibitors; D014361:Trypsin Inhibitors; D010450:Endopeptidases; D012697:Serine Endopeptidases; C037902:isatoic anhydride