2-Saccharinylmethyl aryl and aryloxy acetates useful as proteolytic enzyme inhibitors and pharmaceutical compositions contaning them.

摘要

4-R<4>-R<5>-2-Saccharinylmethyl aryl and aryloxy acetates, having the formula: <CHEM> wherein: m is zero or one, n is zero or one, and the sum of m + n is zero or one; R<1> is hydrogen or lower-alkyl; R<2> is hydrogen or lower-alkyl; R<3> is phenyl or phenyl substituted by from one to three, the same or different, members of the group consisting of lower-alkyl perfluorolower-alkyl, lower-alkoxy and halogen; R<4> is hydrogen, halogen, lower-alkyl, perfluorolower-alkyl, perchlorolower-alkyl, lower-alkenyl, lower-alkynyl, cyano, carboxamido, amino, lower-alkylamino, dilower-alkylamino, lower-alkoxy, benzyloxy, lower-alkoxycarbonyl, hydroxy or phenyl; and R<5> is hydrogen or from one to two substituents in any of the 5-, 6- or 7-positions. The compounds of the present invention inhibit the activity of serine proteases, specifically human leukocyte elastase and the chymotrypsin-like enzymes, and are thus useful in the treatment of degenerative disease conditions such as emphysema, rheumatoid arthritis, pancreatitis, cysticfibrosis, chronic bronchitis, adult respiratory distress syndrome, inflammatory bowel disease, psoriasis, bullous pemphigoid and alpha-1-antitrypsin deficiency.