Substituted 4-phenoxy and 4-phenylthio prolines

Claim 1

A compound of the formula and a pharmaceutically acceptable salt thereof wherein X is oxygen or sulfur; -A 1 -A 2 - is -CH-NH- or -C=N- ; A is or 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 R 3 is hydrogen, lower alkyl, halo substituted lower alkyl, phenyl, benzyl, phenethyl or cycloalkyl; R 4 is hydrogen or R 5 is lower alkyl, or 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, 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, 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-guanidinyl, R 12 is alkyl of 1 to 10 carbons, or 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 R 15 is hydrogen, lower alkyl, cycloalkyl or phenyl; R 16 is hydrogen, lower alkyl, lower alkoxy, cycloalkyl, phenyl, benzyl, or phenethyl; and R 14 is hydrogen, lower alkyl, cycloalkyl-(CH 2 ) n -, halo substituted lower alkyl, hydroxy substituted lower alkyl, -(CH 2 ) q -N(lower alkyl) 2 , or -(CH 2 ) q -NH 2 .