Phosphonyl hydroxyacyl amino acid derivatives as antihypertensives

Claim 1

A compound of the formula and pharmaceutically acceptable salts thereof wherein: X is R 4 is hydrogen, lower alkyl, halogen, keto, hydroxy, 0 alkyl, azido, amino, a 1- or 2-naphthyl of the formula -(CH 2 ) m -cycloalkyl, -0-lower alkyl, a 1- or 2-naphthyloxy of the formula -S-lower alkyl, , or a 1- or 2-naphthylthio of the formula R 5 is keto, halogen, , -O-lower alkyl, a 1- or 2-naphthyloxy of the formula , -S-lower alkyl, or a 1- or 2-naphthylthio of the formula R 7 . is keto or each R 8 is the same or different and is halogen or Y-R 14 ; R 9 , R ' 9 , R 10 and R ' 10 are independently selected from hydrogen and lower alkyl or R ' 9 , R 10' R ' 10 are hydrogen and R 9 is R 11 is hydrogen, 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 12 is hydrogen, 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 or three; p is one, two or three provided that p is more than one only if R 11 or R 12 is hydrogen, methyl, methoxy, chloro, or fluoro; R 13 is hydrogen or lower alkyl of 1 to 4 carbons; Y is oxygen or sulfur; R 14 is lower alkyl of 1 to 4 carbons, , or the R 14 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 21 is hydrogen, lower alkyl, cycloalkyl, phenyl or R 22 is hydrogen, lower alkyl, (CH 2 ) r -NH 2 , (CH 2 ) r -SH, -(CH 2 ) r -S-lower alkyl, r is an integer from 1 to 4; R 1 is alkyl of 1 to 10 carbons, aminoalkyl, haloalkyl, -(CH 2 ) q -cycloalkyl, or wherein q is zero or an integer from 1 to 7 and R 11 and p are as defined above; and R 19 and R 20 are independently selected from the group consisting of hydrogen, lower alkyl, halo substituted lower alkyl, or wherein m, R 11 and p are as defined above; R 2 is hydrogen, lower alkyl, halo substituted lower alkyl, -(CH 2 ) r -NH 2 , -(CH 2 ) r -SH, -(CH 2 ) r -S-lower alkyl, wherein r is as defined hereinbefore; R 3 and R 6 are independently selected from hydrogen, lower alkyl, benzyl, benzhydryl, alkali metal, or wherein R 15 is hydrogen, lower alkyl, cycloalkyl, or phenyl, and R 16 is hydrogen, lower alkyl, lower alkoxy, phenyl, or R 15 and R 16 taken together are -(CH 2 ) 2 -, -(CH 2 ) 3' -CH = CH- or R 17 is lower alkyl, benzyl, or phenethyl; and R 18 is hydrogen, lower alkyl, benzyl, or phenethyl.