Carboxyalkyl dipeptides as antiglaucoma agents

Claim 1

A method for reducing elevated intraocular pressure in a mammal which comprises topically administering to an eye of said mammal a composition comprising an intraocular pressure reducing effective amount of a compound represented by the formulae: ##STR12## or their isomers or pharmaceutically acceptable salts thereof, in combination with an ophthamologically acceptable carrier for topical use, wherein A is --SO 2 --; X is Cl or CF 3 ; Y is ##STR13## Z is ##STR14## B is ##STR15## R 1 is hydrogen or lower alkyl; R 2 and R 5 are independently hydrogen, lower alkyl, phenyl, or phenyl(lower)alkyl; R 3 and R 4 are independently hydrogen, lower alkyl, haloloweralkyl, phenyl, or phenyl(lower)alkyl, or R 3 and R 4 taken together with the carbon to which they are attached can form a 5-7 membered cycloalkyl ring; R 6 and R 8 are independently hydroxy, alkoxy having from 1 to 8 carbon atoms, L--Q r --(CH 2 ) s --O--, wherein L is phenyl, substituted phenyl, 1-naphthyl or 2-naphthyl; Q is oxygen or sulfur; r is 0 or 1 and s is 0 to 4; and wherein the substituents on the phenyl are chosen from group M, wherein M is halogen, hydroxy, trifluoromethyl, alkoxy having from 1 to 6 carbon atoms, alkyl from 1 to 6 carbon atoms, 2-furanyl, 3-furanyl, 2-thienyl, 3-thienyl and phenyl (which phenyl group may be substituted with halogen, hydroxy, trifluoromethyl, alkoxy having from 1 to 6 carbon atoms or alkyl having from 1 to 6 carbon atoms); provided that when s is zero, r is zero; --OCH 2 --OCO--alkyl wherein the alkyl has from 3 to 8 carbon atoms, --OCH 2 CO--phenyl, wherein the phenyl may be substituted with group M, 1-gylceryl, ##STR16## R 7 is hydrogen, lower alkyl, or aminoloweralkyl; R 9 is hydrogen, lower alkyl, unsubstituted or substituted phenyl, and substituted or unsubstituted phenyl lower alkyl, wherein phenyl may be substituted by group M; R 10 is hydrogen or lower alkyl; a is 0-8; b is 1-8; c is 2-8; m is 1-4; n is 0 or 1; p and q are each 0, 1 or 2, provided that in formulae IIIb and IIIc the sum of p and q is 1 or 2, and that in formulae IIId, p is not 0.

Claim 2

A method for reducing elevated intraocular pressure in a mammal which comprises topically administering to an eye of said mammal a composition comprising an intraocular pressure reducing effective amount of a compound represented by the formulae: ##STR12## or their isomers or pharmaceutically acceptable salts thereof, in combination with an ophthamologically acceptable carrier for topical use, wherein A is --SO 2 --; X is Cl or CF 3 ; Y is ##STR13## Z is ##STR14## B is ##STR15## R 1 is hydrogen or lower alkyl; R 2 and R 5 are independently hydrogen, lower alkyl, phenyl, or phenyl(lower)alkyl; R 3 and R 4 are independently hydrogen, lower alkyl, haloloweralkyl, phenyl, or phenyl(lower)alkyl, or R 3 and R 4 taken together with the carbon to which they are attached can form a 5-7 membered cycloalkyl ring; R 6 and R 8 are independently hydroxy, alkoxy having from 1 to 8 carbon atoms, L--Q r --(CH 2 ) s --O--, wherein L is phenyl, substituted phenyl, 1-naphthyl or 2-naphthyl; Q is oxygen or sulfur; r is 0 or 1 and s is 0 to 4; and wherein the substituents on the phenyl are chosen from group M, wherein M is halogen, hydroxy, trifluoromethyl, alkoxy having from 1 to 6 carbon atoms, alkyl from 1 to 6 carbon atoms, 2-furanyl, 3-furanyl, 2-thienyl, 3-thienyl and phenyl (which phenyl group may be substituted with halogen, hydroxy, trifluoromethyl, alkoxy having from 1 to 6 carbon atoms or alkyl having from 1 to 6 carbon atoms); provided that when s is zero, r is zero; --OCH 2 --OCO--alkyl wherein the alkyl has from 3 to 8 carbon atoms, --OCH 2 CO--phenyl, wherein the phenyl may be substituted with group M, 1-gylceryl, ##STR16## R 7 is hydrogen, lower alkyl, or aminoloweralkyl; R 9 is hydrogen, lower alkyl, unsubstituted or substituted phenyl, and substituted or unsubstituted phenyl lower alkyl, wherein phenyl may be substituted by group M; R 10 is hydrogen or lower alkyl; a is 0-8; b is 1-8; c is 2-8; m is 1-4; n is 0 or 1; p and q are each 0, 1 or 2, provided that in formulae IIIb and IIIc the sum of p and q is 1 or 2, and that in formulae IIId, p is not 0.