2-saccharinylmethyl aryl carboxylates useful as proteolytic enzyme inhibitors and compositions and method of use thereof

A compound having the formula:

• ##STR24## wherein:
• Ar is phenyl, naphthyl or anthryl or such groups substituted by from one to three, the same or different, members of the group consisting of lower-alkyl, perfluorolower-alkyl, perchlorolower-alkyl, lower-alkoxy, halogen, nitro, cyano, carboxy, PO(lower-alkoxy).sub.2, amino, lower-alkylamino, dilower-alkylamino, lower-alkanoylamino, lower-alkoxycarbonyl, hydroxy, benzyloxy, carboxylower-alkoxy, --O-(alkylene)-1-lower-alkyl-4-piperidinyl, --O-(alkylene) -1-lower-alkyl-2- or 3-pyrrolidinyl, --SO.sub.2 --N.dbd.B, --CO--N.dbd.B, -(alkylene)-N.dbd.B, --COO(alkylene)-N.dbd.B, --NH-(alkylene)-N.dbd.B;
• --N(lower-alkyl)-(alkylene)-N.dbd.B or --O-(alkylene)-N.dbd.B, where N.dbd.B in each instance is amino, lower-alkylamino, dilower-alkylamino, 1-azetidinyl, 1-pyrrolidinyl, 1-piperidinyl, 4-morpholinyl, 1-piperazinyl, 4-lower-alkyl-1-piperazinyl, 4-benzyl-1-piperazinyl, 1-imidazolyl, carboxy-lower-alkylamino or --NR-(alkylene)-N(alkyl).sub.2, where R is lower alkyl;
• R.sup.4 is hydrogen, halogen, lower-alkyl, perfluorolower-alkyl, perchlorolower-alkyl, polyfluorolower-alkyl, polychlororlower-alkyl, lower-alkenyl, lower-alkynyl, cyano, amino, lower-alkylamino, dilower-alkylamino, lower-alkoxy, benzyloxy, lower-alkoxycarbonyl, phenyl or carboxamido;
• and
• R.sup.5 is hydrogen or from one to two the same or different substituents in any of the 5-, 6- or 7-positions selected from halogen, cyano, nitro, N.dbd.B, 1-lower-alkyl-2-pyrrolyl, lower-alkylsulfonylamino, polyfluorolower-alkylsulfonylamino, polychlorolower-alkylsulfonylamino, aminosulfonyl, lower-alkyl, polyfluorolower-alkyl, polychlorolower-alkyl, cycloalkyl, lower-alkoxy, hydroxy, carboxy, carboxamido, hydroxylower-alkyl, methylenedioxy, cycloalkoxy, formyl, aminomethyl, lower-alkylsulfonyl, polyfluorolower-alkylsulfonyl, polychlorolower-alkylsulfonyl, lower-alkylsulfonylaminosulfonyl, lower-alkoxypoly-lower-alkyleneoxy, benzyloxypolylower-alkyleneoxy, hydroxypoly-lower-alkyleneoxy, benzyloxylower-alkoxy, hydroxylower-alkoxy, polyhydroxylower-alkoxy or said hydroxy groups of polyhydroxylower-alkoxy substituted by benzyl;
• poly(lower-alkoxy) lower-alkoxy, --SR, --SOR, --SO.sub.2 R, --OCOR, --O-(alkylene)-COOR, --O-(alkylene)-COOH, --O-(alkylene)-N.dbd.B, --O--C(R').sub.2 COOH, --O--C(R').sub.2 --COOR, --O--C(X').sub.2 COOH, --O--C(X').sub.2 COOR, --O--(CH.sub.2).sub.n OC(O) (CH.sub.2).sub.n --N.dbd.B, --O--(CH.sub.2).sub.n --O--(CH.sub.2).sub.n OC(O) (CH.sub.2).sub.n --N.dbd.B, --O--(CH.sub.2 O).sub.m --A, --O--(CH.sub.2).sub.n -(5-((CH.sub.2).sub.n --N.dbd.B) -2-furanyl), --O--(CH.sub.2).sub.n -(5-((CH.sub.2).sub.n --N.dbd.B)-2-thienyl), --O--(CH.sub.2).sub.n -(5-((CH.sub.2).sub.n --N.dbd.B)-1-R-2-pyrrolyl), --O--(CH.sub.2).sub.m --C(O)--N.dbd.B", --O--(CH.sub.2).sub.n --.tbd.--(CH.sub.2).sub.n --N.dbd.B'", --O--(CH.sub.2).sub.n --.dbd.--(CH.sub.2).sub.n --N.dbd.B'", aminosulfonyloxy, or dilower-alkylaminosulfonyloxy, wherein R is lower-alkyl, phenyl, benzyl, 1,1-diphenylmethyl, or naphthyl, or phenyl or napthyl substituted by from one to two substituents selected from lower-alkyl, lower-alkoxy or halogen;
• N.dbd.B has the meanings given above;
• each R' group is independently hydrogen, or lower-alkyl;
• X' is chlorine or fluorine;
• n is an integer from one to four;
• m is an integer from zero to four;
• A is an azetidinyl, pyrrolidinyl, or piperidinyl ring attached through any available carbon atom, or said ring substituted on nitrogen by an R substitutent wherein R is as defined above;
• N.dbd.B" is amino, lower-alkylamino, dilower-alkylamino, dibenzylamino, 1-azetidinyl, 1-pyrrolidinyl, 1-piperidinyl, 4-morpholinyl, 1-piperazinyl, 4-lower-alkyl-1-piperazinyl, 4-benzyl-1-piperazinyl, 4-tert-butoxycarbonyl-1-piperazinyl, 1-imidazolyl, or --NR"(alkylene)-N(alkyl).sub.2 wherein R" is hydrogen or lower-alkyl;
• and N.dbd.B'" is amino, lower-alkylamino, dilower-alkylamino, dibenzylamino, 1-azetidinyl, 1-pyrrolidinyl, 1-piperidinyl, 4-morpholinyl, 1-piperazinyl, 4-lower-alkyl-1-piperazinyl, 4-benzyl-1-piperazinyl, 1-imidazolyl, or --NR"(alkylene)-N(alkyl).sub.2 wherein R" is hydrogen or lower-alkyl;
• or acid-addition salts of basic members thereof or base-addition salts of acidic members thereof, with the proviso that, when R.sup.4 and R.sup.5 are independently either H or lower alkyl, then Ar cannot be either phenyl, 2,4-dichlorophenyl or 4-nitrophenyl.