Angiotensinogen analogs

摘要

The invention relates to renin inhibiting compounds of the formula wherein A is hydrogen; loweralkyl; arylalkyl; OR10 or SR10 wherein R10 is hydrogen, loweralkyl or aminoalkyl; NR11R12 wherein R11 and R12 are independently selected from hydrogen, loweralkyl, aminoalkyl, cyanoalkyl and hydroxyalkyl; wherein B is NH, alkylamino, S, O, CH2 or CHOH and R13 is loweralkyl, cycloalkyl, aryl, arylalkyl, alkoxy, alkenyloxy, hydroxyalkoxy, dihydroxyalkoxy, arylalkoxy, arylalkoxyalkyl, amino, alkylamino, dialkylamino, (hydroxyalkyl)(alkyl)amino, (dihydroxyalkyl)(alkyl)amino, aminoalkyl, alkoxycarbonylalkyl, carboxyalkyl, N-protected aminoalkyl, alkylaminoalkyl, (N-protected)(alkyl)aminoalkyl, dialkylaminoalkyl, (heterocyclic) alkyl or a substituted or unsubstituted heterocyclic; W is CO or CHOH and U is CH2 or NR2 with the proviso that when W is CHOH then U is CH2; R1 is loweralkyl, cycloaklylmethyl, benzyl, alpha , alpha -dimethylbenzyl, 4-methoxybenzyl, halobenzyl, (1-naphthyl)methyl, (2-naphthyl)methyl, (4-imidazoyl)-methyl, phenethyl, phenoxy, thiophenoxy or anilino; provided if R1 is phenoxy, thiophenoxy or anilino, B is CH2 or CHOH or A is hydrogen, R3 is loweralkyl, vinylloweralkyl, benzyl or heterocyclic ring substituted methyl, R5 is loweralkyl, cycloalkylmethyl or benzyl; R2 and R4 are independently selected from hydrogen and loweralkyl; R6 is CHOH or CO; R7 is CH2, CF2 or CF with the proviso that when R6 is CO, R7 is CF2; R8 is CH2, CHR14 wherein R14 is lower-alkyl, cycloalkyl, cycloalkylalkyl, aryl or arylalkyl, or R7 and R8 taken together can be with the proviso that when R7 is CF2, R8 is CH2; E is O, S, SO, SO2, NR15 wherein R15 is hydrogen or loweralkyl or NR16CO wherein R16 is hydrogen or loweralkyl; R9 is loweralkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl or an N-protected group, or E and R9 taken together can be N3, with the proviso that when E is NH, R9 is an N-protecting group; and pharmaceutically acceptable salts thereof.