Tripeptide renin inhibitors

A compound of the formula:

• ##STR57## wherein X is ##STR58## R.sup.1 is hydrogen, C.sub.1 -C.sub.4 -alkyl, hydroxy-C.sub.1 -C.sub.4 -alkyl, aryl, as defined below, indolyl, 4-imidazolyl, amino-C.sub.2 -C.sub.4 -alkyl, Guanidyl-C.sub.2 -C.sub.3 -alkyl or methylthiomethyl;
• R.sup.29 and R.sup.26 are independently hydrogen, or W-(CH.sub.2)n in which W is hydrogen, C.sub.1 -C.sub.4 -alkyl, aryl, wherein aryl is unsubstituted or mono-, di or trisubstituted phenyl or naphthyl where each substituent is independently selected from the group consisting of C.sub.1 -C.sub.8 -alkyl, amino, mono-or di-C.sub.1 -C.sub.4 -alkylamino, amino-C.sub.1 -C.sub.4 -alkyl, hydroxy-C.sub.1 -C.sub.4 -aklyl, mono- or di-C.sub.1 -C.sub.4 -aklylamino-C.sub.1 -C.sub.4 -alkyl, guanidyl, guanidyl-C.sub.1 -C.sub.4 -alkoxy, CF.sub.3, halo, CO.sub.2 H, CO.sub.2 -C.sub.1 -C.sub.4 -alkyl, CO.sub.2 -C.sub.1 -C.sub.4 - alkoxy, NR.sup.5 R.sup.6, and N(R.sup.5)+.sub.3 A-,
• wherein R.sup.5 and R.sup.6 are independently hydrogen, unsubstituted C.sub.1 -C.sub.4 -alkyl, and A- is an anion, and n is 0 to 5;
• except that when X is --0-- only one of R.sup.29 or R.sup.26 is present;
• E is absent;
• or ##STR59## where r is 1 to 4;
• and R.sup.3 is hydrogen;
• C.sub.1 -C.sub.4 -alky;
• aryl, as defined above;
• aryl-C.sub.1 -C.sub.4 -alkyl;
• or indolyl;
• ##STR60## wherein R.sup.7 is C.sub.3 -C.sub.6 -alkyl;
• aryl, as defined above;
• or unsubstituted or mono-, di- or trisubstituted C.sub.3 -C.sub.7 -cycloalkyl, wherein each substituent is independently selected from the group consisting of C.sub.1 -C.sub.4 -alkyl, trifluoromethyl, hydroxy, C.sub.1 -C.sub.4 -alkoxy, and halo;
• and s is 0 to 4;
• R.sup.7a is hydrogen;
• C.sub.1 -C.sub.8 -alkyl;
• C.sub.2 -C.sub.8 -alkenyl;
• mono or disubstituted C.sub.2 -C.sub.8 -alkyl, wherein the substituent (s) is/are on the final 1 and/or 2 carbon atoms of the alkyl chain and is/are independently selected from the group consisting of hydroxy aryl, as defined above;
• unsubstituted or mono-, di- or trisubstituted C.sub.3 -C.sub.7 -cycloalkyl, wherein each substituent is independently selected from the group consisting of C.sub.1 -C.sub.4 -alkyl, trifluoromethyl, hydroxy, C.sub.1 -C.sub.4 -alkoxy, and halo;
• R.sup.7, X.sup.1 and r are as defined above;
• and wherein the first alternate G definition of the above formula has a 2S or 2R, 3S, 4S configuration;
• and J is Y-(CH.sub.2)x [CH(R.sup.5)]y-(CH.sub.2)z-R.sup.10 wherein Y is oxygen, NH, or N-C.sub.1 -C.sub.4 -alkyl, x and y are independently zero, 1, 2, or 3 and z is zero or one;
• R.sup.10 is a quarternized 5 to 7 membered heterocyclic ring containing N.sup.+ A.sup.- ;
• quaternized ring containing one additional heteroatom selected from N, NO, O, S, SO or SO.sub.2 ;
• a quaternized ring as defined containing a substituent on the ring carbon in which the substituent on the ring carbon in which the substituent is selected from --OH, --CO.sub.2 H, --SO.sub.3 H, --SO.sub.2 NH.sub.2, -aryl as defined above, --CF.sub.3, --halo, or unsubstituted mono, or di-C.sub.1 -C.sub.4 -alkylamino;
• a quaternized ring as defined in which the nitrogen is substituted by R.sup.11 and R.sup.12 as defined below;
• or the quaternized nitrogen is fused with a second ring having 4 to 6 carbon atoms forming a spiro-fused ring system, or fused with a --(CH.sub.2).sub.2 --O--(CH.sub.2).sub.2 -- substituent;
• ##STR61## in which xl is 1, 2 or 3;
• ##STR62## in which Y.sup.1 is zero or 1 and X is absent, oxygen or NH;
• ##STR63## in which Z.sup.1 is 1 or 2, A- is an anion, and R.sup.12a and R.sup.12b have the same significance as R.sup.12 ;
• R.sup.11 is C.sub.1 -C.sub.4 alkyl, substituted C.sub.1 -C.sub.4 alkyl in which the substituent is --OH, --CO.sub.2 H, --SO.sub.3 H, --SO.sub.2 NH.sub.2, -aryl as defined above, -halo, unsubstituted, mono or di-C.sub.1 -C.sub.4 alkylamino-;
• a non-quaternized 5 or 6 membered heterocyclic ring containing a nitrogen and an additional heteroatom selected from N, NO, O, S, SO.sub.2 or SO.sub.2, or a 5 or 6 memebered heterocyclic ring containing one nitrogen and one additional heteroatom as defined and substituted with one or two C.sub.1 -C.sub.4 alkyl;
• R.sup.12 is C.sub.1 -C.sub.4 alkyl;
• and, -NR.sup.11 R.sup.12a R.sup.12b +A- in which R.sup.11 is as defined above and R.sup.12a and R.sup.12b independently have the same significance as R.sup.12 and A- is as defined above.