Substituted 4-phenoxy or 4-phenylthio prolines

Claim 1

A compound of the formula ##STR107## and a pharmaceutically acceptable salt thereof wherein X is oxygen or sulfur; --A 1 -A 2 -- is --CH--NH-- or --C═N--; A is ##STR108## p is one, two, three or four; R, R 8 and R 9 are independently selected from the group consisting of hydrogen, lower alkyl, benzyl, benzhydryl, and salt forming ion; R 1 and R 2 are independently selected from the group consisting of hydrogen, halogen, lower alkyl, lower alkoxy, halo substituted lower alkyl, nitro, and --SO 2 NH 2 ; Z is ##STR109## R 3 is hydrogen, lower alkyl, halo substituted lower alkyl, phenyl, benzyl, phenethyl or cycloalkyl; R 4 is hydrogen or ##STR110## R 5 is lower alkyl, ##STR111## n is zero, one, two, three or four; R 6 is hydrogen, lower alkyl, lower alkoxy, halogen, or hydroxy; R 7 is lower alkyl or cycloalkyl; R 10 is hydrogen, lower alkyl, ##STR112## halo substituted lower alkyl, hydroxy substituted lower alkyl, --(CH 2 ) q -cycloalkyl, --(CH 2 ) q -N(lower alkyl) 2 , --(CH 2 ) q --NH 2 , --(CH 2 ) q -carboxy, --(CH 2 ) q --SH, --(CH 2 ) q -S-lower alkyl, ##STR113## q is one, two, three or four; R 11 is hydrogen, lower alkyl, halo substituted lower alkyl, hydroxy substituted lower alkyl, --(CH 2 ) q --NH 2 , --(CH 2 ) q -N(lower alkyl) 2 , --(CH 2 ) q -quanidinyl, ##STR114## R 12 is alkyl of 1 to 10 carbons, ##STR115## cycloalkyl--(CH 2 ) m --; m is zero or an integer from 1 to 7; R 13 is hydrogen, lower alkyl, benzyl, benzhydryl, salt forming ion or ##STR116## R 15 is hydrogen, lower alkyl, cycloalkyl or phenyl; p0 R 16 is hydrogen, lower alkyl, lower alkoxy, cycloalkyl, phenyl, benzyl, or phenethyl; and R 14 is hydrogen, lower alkyl, cycloalkyl-(CH 2 ) n --, ##STR117## halo substituted lower alkyl, hydroxy substituted lower alkyl, --(CH 2 ) q --N(lower alkyl) 2 , or --(CH 2 ) q --NH 2 .