α-acyloxy phosphonate angiotensin converting enzyme inhibitors

Claim 1

A compound of the formula ##STR182## including a pharmaceutically acceptable salt thereof wherein: R 1 is hydrogen, lower alkyl, --(CH 2 ) r --Cl, --(CH 2 ) r --Br, --(CH 2 ) r --F, --CF 3 , ##STR183## --(CH 2 ) r -cycloalkyl, --(CH 2 ) r --NH 2 , --(CH 2 ) r --SH, --(CH 2 ) r --S-lower alkyl, ##STR184## R 2 is lower alkyl, ##STR185## --(CH 2 ) r -cycloalkyl, or --(CH 2 ) r --NH 2 ; R 3 and R 6 are independently selected from hydrogen, lower alkyl, benzyl, benzhydryl, alkali metal salt ion, alkaline earth metal salt ion, ##STR186## and --(CH 2 ) 2 Si(CH 3 ) 3 ; R 4 is straight or branched chain alkyl of 1 to 10 carbons, --(CH 2 ) q -cycloalkyl, ##STR187## or --(CH 2 ) r --NH 2 ; r is an integer from 1 to 7; q is zero or an integer from 1 to 7; X is an amino or imino acid or ester of the formula ##STR188## R 7 is hydrogen, lower alkyl, halogen, hydroxy, ##STR189## a 1- or 2-naphthyl of the formula ##STR190## a substituted 1- or 2-naphthyl of the formula ##STR191## a 1- or 2- naphthyloxy of the formula ##STR192## a substituted 1- or 2-naphthyloxy of the formula ##STR193## 1- or 2-naphthylthio of the formula ##STR194## or a substituted 1- or 2-naphthylthio of the formula ##STR195## R 8 is lower alkyl, halogen, ##STR196## --O-lower alkyl, a 1- or 2-naphthyloxy of the formula ##STR197## a substituted 1- or 2-naphthyloxy of the formula ##STR198## a 1- or 2-naphthylthio of the formula ##STR199## or a substituted 1- or 2-naphthylthio of the formula ##STR200## R 9 is lower alkyl, keto, ##STR201## R 10 is halogen or Y--R 16 ; R 11 , R' 11 , R 12 and R' 12 are independently selected from hydrogen and lower alkyl or R' 11 , R 12 and R' 12 are hydrogen and R 11 is ##STR202## R 13 is lower alkyl of 1 to 4 carbons, lower alkoxy of 1 to 4 carbons, lower alkylthio of 1 to 4 carbons, chloro, bromo, fluoro, trifluoromethyl, hydroxy, phenyl, phenoxy, phenylthio, or phenylmethyl; R 5 is lower alkyl of 1 to 4 carbons, lower alkoxy of 1 to 4 carbons, lower alkylthio of 1 to 4 carbons, chloro, bromo, fluoro, trifluoromethyl or hydroxy; m is zero, one, two, three, or four; p is one, two or three provided that p is more than one only if R 13 or R 5 is methyl, methoxy, chloro, bromo, or fluoro; R 14 is hydrogen, lower alkyl, ##STR203## R 15 is hydrogen or lower alkyl of 1 to 4 carbons; Y is oxygen or sulfur; R 16 is lower alkyl of 1 to 4 carbons, ##STR204## or the R 16 groups join to complete an unsubstituted 5- or 6-membered ring or said ring in which one or more of the carbons has a lower alkyl of 1 to 4 carbons or a di(lower alkyl of 1 to 4 carbons) substituent; R 17 is hydrogen, lower alkyl, cycloalkyl, or phenyl; R 18 is hydrogen, lower alkyl, lower alkoxy, or phenyl; n is zero, one, or two; R 19 is lower alkyl or ##STR205## R 20 is hydrogen, lower alkyl, ##STR206## R 21 is hydrogen, lower alkyl ##STR207## --(CH 2 ) r --NH 2 , --(CH 2 ) r --SH, --(CH 2 ) 2 --S-lower alkyl, ##STR208## R 22 is lower alkyl, benzyl, or phenethyl; and R 23 is hydrogen, lower alkyl, benzyl, or phenethyl.