Journal of Medicinal Chemistry 1986-04-01

Substituted isatoic anhydrides: selective inactivators of trypsin-like serine proteases.

M H Gelb, R H Abeles

Index: J. Med. Chem. 29(4) , 585-9, (1986)

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Abstract

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.