Renin inhibitory peptides

Claim 2

A peptide of the formula: wherein: A is hydrogen; where n is 0 to 5 and R 3 has the same meaning as set out further below, and may additionally be hydrogen; B is absent; glycyl; sarcosyl; or D is absent; or where Z is (CH 2 ) n and n is 1 or 2; or -S-; R 1 is hydrogen; C 1-4 alkyl; hydroxy C 1-4 alkyl; phenyl; phenyl mono-substituted with a member selected from the group consisting of methyl, trifluoromethyl, hydroxy, methoxy, fluoro, chloro, bromo, and iodo; indolyl; 4-imidazolyl; amine C 2-4 alkyl; guanidyl C 2-3 alkyl; or methylthiomethyl; R is hydrogen; C 1-4 alkyl; phenyl; phenyl mono-substituted with a member selected from the group consisting of methyl, trifluoromethyl, hydroxy, methoxy, fluoro, chloro, bromo, and iodo; or indolyl; R 3 is C 3-6 alkyl; C 3-7 cycloalkyl; phenyl; or phenyl mono-substituted with a member selected from the group consisting of methyl, trifluoromethyl, hydroxy, methoxy, fluoro, chloro, bromo, and iodo: R4 is hydrogen; or where R is hydrogen; C 1-4 alkyl; hydroxy; or C 3-7 cycloalkyl; and R 2 is as defined above; R 5 is hydrogen; where R 6 is hydrogen, C 1-4 alkyl, hydroxy, or C 3-7 cycloalkyl, and R 2 is as defined above; or -CH 2 -R 7 , where R 7 is 4-imidazolyl, amino C 2-4 alkyl, 2-, 3-, or 4-pyridyl, or guanidyl C 2-3 alkyl; and E is OR 8 ; NH R 8 , or N(R 8 ) 2 , where each R 8 may be the same or different and is hydrogen or C 1-4 alkyl; wherein all of the asymmetric carbon atoms have an S configuration, except those of substituents B and D, which may also have the R configuration; and a pharmaceutically acceptable salt thereof.

Claim 3

A peptide. according to Claim 1 wherein the peptide is iso-butyryl-His-Pro-Phe-His-Sta-Val-His-Gl y- N H 2 .

Claim 4

A peptide according to Claim 1 wherein the peptide is iso-butyryl-His-Pro-Phe-His-Sta-Ile-His-NH 2 .

Claim 5

A peptide according to Claim 1 wherein the peptide is tert-butyloxycarbonyl-Phe-His-Sta-Ile-His-NH 2 .

Claim 6

A peptide according to Claim 1 wherein the peptide is benzyloxycarbonyl-Phe-His-Sta-Ile-His-N H 2 .

Claim 7

A pharmaceutical composition for treating renin-associated. hypertension, comprising a pharmaceutical carrier and a therapeutically effective amount of a peptide of the formula:

Claim 8

A pharmaceutical composition for treating renin-associated. hypertension, comprising a pharmaceutical carrier and a therapeutically effective amount of a peptide of the formula:

Claim 9

wherein: A is where n is 0 to 5 and R 3 has the same meaning as set out further below, and may additionally be hvdroqen; B is absent; glycyl; sarcosyl; or D is absent; or where Z is (CH 2 ) n and n is 1 or 2; or - S -; R 1 is hydrogen; C 1-4 alkyl; hydroxy C l-4 alkyl; phenyl; phenyl mono-substituted with a member selected from the group consisting of methyl, trifluoromethyl, hydroxy, methoxy, fluoro, chloro, bromo, and iodo; indolyl; 4-imidazolyl; amine C 2-4 alkyl; guanidyl C 2 - 3 alkyl; or methylthiomethyl; R is hydrogen; C 1-4 alkyl; phenyl; phenyl mono-substituted with a member selected from the group consisting of methyl, trifluoromethyl, hydroxy, methoxy, fluoro, chloro, bromo, and iodo; or indolyl; R 3 is C 3-6 alkyl; C 3-7 cycloalkyl; phenyl; or phenyl mono-substituted with a member selected from the group consisting of methyl, trifluoromethyl, hydroxy, methoxy, fluoro, chloro, bromo, and iodo; R 4 is hydrogen; or where R 6 is hydrogen; C 1-4 alkyl; hydroxy; or C 3-7 cycloalkyl; and R 2 is as defined above; R 5 is hydrogen; where R 6 is hydrogen, C l-4 alkyl, hydroxy, or 3-7 cycloalkyl, and R 2 is as defined above; or -CH 2 -R 7 , where R 7 is 4-imidazolyl, amino C 2-4 alkyl, 2-, 3-, or 4-pyridyl, or guanidyl C 2-3 alkyl; and E is OR 8 ; NHR 8 , or N(R 8 ) 2 , where each R 8 may be the same or different and is hydrogen or C 1-4 alkyl; wherein all of the asymmetric carbon atoms have an S configuration, except those of substituents B and D, which may also have the R configuration; and a pharmaceutically acceptable salt thereof.

Claim 10

wherein: A is where n is 0 to 5 and R 3 has the same meaning as set out further below, and may additionally be hvdroqen; B is absent; glycyl; sarcosyl; or D is absent; or where Z is (CH 2 ) n and n is 1 or 2; or - S -; R 1 is hydrogen; C 1-4 alkyl; hydroxy C l-4 alkyl; phenyl; phenyl mono-substituted with a member selected from the group consisting of methyl, trifluoromethyl, hydroxy, methoxy, fluoro, chloro, bromo, and iodo; indolyl; 4-imidazolyl; amine C 2-4 alkyl; guanidyl C 2 - 3 alkyl; or methylthiomethyl; R is hydrogen; C 1-4 alkyl; phenyl; phenyl mono-substituted with a member selected from the group consisting of methyl, trifluoromethyl, hydroxy, methoxy, fluoro, chloro, bromo, and iodo; or indolyl; R 3 is C 3-6 alkyl; C 3-7 cycloalkyl; phenyl; or phenyl mono-substituted with a member selected from the group consisting of methyl, trifluoromethyl, hydroxy, methoxy, fluoro, chloro, bromo, and iodo; R 4 is hydrogen; or where R 6 is hydrogen; C 1-4 alkyl; hydroxy; or C 3-7 cycloalkyl; and R 2 is as defined above; R 5 is hydrogen; where R 6 is hydrogen, C l-4 alkyl, hydroxy, or 3-7 cycloalkyl, and R 2 is as defined above; or -CH 2 -R 7 , where R 7 is 4-imidazolyl, amino C 2-4 alkyl, 2-, 3-, or 4-pyridyl, or guanidyl C 2-3 alkyl; and E is OR 8 ; NHR 8 , or N(R 8 ) 2 , where each R 8 may be the same or different and is hydrogen or C 1-4 alkyl; wherein all of the asymmetric carbon atoms have an S configuration, except those of substituents B and D, which may also have the R configuration; and a pharmaceutically acceptable salt thereof.

Claim 11

A pharmaceutical composition for treating renin-associated hyperaldosteronism, comprising a pharmaceutical carrier and a therapeutically effective amount of a peptide of the formula wherein: A is hydrogen; where n is 0 to 5 and R 3 has the same meaning as set out further below, and may additionally hydrogen; B is absent; glycyl; sarcosyl; or D is absent; or where Z is (CH 2 ) n and n is 1 or 2; or -S-; R 1 is hydrogen; C 1-4 alkyl; hydroxy C 1-4 alkyl; phenyl; phenyl mono-substituted with a member selected from the group consisting of methyl, trifluoromethyl, hydroxy, methoxy, fluoro, chloro, bromo, and iodo; indolyl; 4-imidazolyl; amine C 2-4 alkyl; guanidyl C 2-3 alkyl; or methylthiomethyl; R 2 is hydrogen; C 1-4 alkyl; phenyl; phenyl mono-substituted with a member selected from the group consisting of methyl, trifluoromethyl, hydroxy, methoxy, fluoro, chloro, bromo, and iodo; or indolyl; R 3 is C 3-6 alkyl; C 3-7 cycloalkyl; phenyl; or phenyl mono-substituted with a member selected from the group consisting of methyl, trifluoromethyl, hydroxy, methoxy, fluoro, chloro, bromo, and iodo; R 4 is hydrogen; or where R 6 is hydrogen; C 1-4 alkyl; hydroxy; or C 3-7 cycloalkyl; R 5 is hydrogen; where R is hydrogen, C 1-4 alkyl, hydroxy, or C 3-7 cycloalkyl, and R 2 is as defined above; or -CH 2 -R 7 , where R 7 is 4-imidazolyl, amino C 2-4 alkyl, 2-, 3-, or 4-pyridyl, or guanidyl C 2-3 alkyl; and E is OR 8 ; NHR 8 , or N(R 8 ) 2 , where each R 8 may be the same or different and is hydrogen or C 1-4 alkyl; wherein all of the asymmetric carbon atoms have an S configuration, except those of substituents B and D, which may also have the R configuration; and a pharmaceutically acceptable salt thereof.

Claim 12

A pharmaceutical composition for treating renin-associated hyperaldosteronism, comprising a pharmaceutical carrier and a therapeutically effective amount of a peptide of the formula wherein: A is hydrogen; where n is 0 to 5 and R 3 has the same meaning as set out further below, and may additionally hydrogen; B is absent; glycyl; sarcosyl; or D is absent; or where Z is (CH 2 ) n and n is 1 or 2; or -S-; R 1 is hydrogen; C 1-4 alkyl; hydroxy C 1-4 alkyl; phenyl; phenyl mono-substituted with a member selected from the group consisting of methyl, trifluoromethyl, hydroxy, methoxy, fluoro, chloro, bromo, and iodo; indolyl; 4-imidazolyl; amine C 2-4 alkyl; guanidyl C 2-3 alkyl; or methylthiomethyl; R 2 is hydrogen; C 1-4 alkyl; phenyl; phenyl mono-substituted with a member selected from the group consisting of methyl, trifluoromethyl, hydroxy, methoxy, fluoro, chloro, bromo, and iodo; or indolyl; R 3 is C 3-6 alkyl; C 3-7 cycloalkyl; phenyl; or phenyl mono-substituted with a member selected from the group consisting of methyl, trifluoromethyl, hydroxy, methoxy, fluoro, chloro, bromo, and iodo; R 4 is hydrogen; or where R 6 is hydrogen; C 1-4 alkyl; hydroxy; or C 3-7 cycloalkyl; R 5 is hydrogen; where R is hydrogen, C 1-4 alkyl, hydroxy, or C 3-7 cycloalkyl, and R 2 is as defined above; or -CH 2 -R 7 , where R 7 is 4-imidazolyl, amino C 2-4 alkyl, 2-, 3-, or 4-pyridyl, or guanidyl C 2-3 alkyl; and E is OR 8 ; NHR 8 , or N(R 8 ) 2 , where each R 8 may be the same or different and is hydrogen or C 1-4 alkyl; wherein all of the asymmetric carbon atoms have an S configuration, except those of substituents B and D, which may also have the R configuration; and a pharmaceutically acceptable salt thereof.