US4384994A
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Renin inhibitory peptides
Assignee: Merck and Co Inc
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Filing: 1981-10-08
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Granted: 1983-05-24
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Expires: 2001-10-08
Abstract
Abstract Renin inhibitory peptides of the formula: Leu--Stav--Val--Phe (I.) and analogs thereof inhibit renin and are useful for treating various forms of renin-associated hypertension and hyperaldosteronism.
Inventors
- 👤 Daniel F. Veber
- 👤 Daniel H. Rich
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-27 04:33
CPC Classifications
C; C07; C07K; C07K5/00; C07K5/02; C07K5/0227; A; A61; A61P; A61P43/00; A61P9/00; A61P9/12; Y; Y10; Y10S; Y10S530/00; Y10S530/86
Claims Analysis
Total Claims: 22
Claim 1
Independent Claim
95 words
A peptide of the formula: ##STR7## wherein: A is hydrogen; or phenoxyacetyl; R 1 is C 3-6 straight or branched alkyl; C 3-7 cycloalkyl; phenyl; or phenyl monosubstituted with hydroxyl, fluoro, chloro, bromo, methyl, or trifluoromethyl; R 2 is hydrogen; or methyl; R 3 is methyl; or isopropyl; R 4 is phenyl; or 4-hydroxyphenyl; and B is OR; NHR; or NR 2 , where each R may be the same or different and is hydrogen or C 1-4 alkyl; and a pharmaceutically acceptable salt thereof; all of the asymmetric carbon atoms having an S configuration.
Claim 2
Dependent Claim
95 words
A peptide of the formula: ##STR7## wherein: A is hydrogen; or phenoxyacetyl; R 1 is C 3-6 straight or branched alkyl; C 3-7 cycloalkyl; phenyl; or phenyl monosubstituted with hydroxyl, fluoro, chloro, bromo, methyl, or trifluoromethyl; R 2 is hydrogen; or methyl; R 3 is methyl; or isopropyl; R 4 is phenyl; or 4-hydroxyphenyl; and B is OR; NHR; or NR 2 , where each R may be the same or different and is hydrogen or C 1-4 alkyl; and a pharmaceutically acceptable salt thereof; all of the asymmetric carbon atoms having an S configuration.
Claim 3
Dependent Claim
21 words
A peptide according to claim 1 wherein the peptide is N-phenoxyacetyl-L-leucyl-(3S,4S)-statyl-L-valyl-L-phenylalanine, or the amide or C 1-4 alkyl ester form thereof.
Claim 4
Dependent Claim
21 words
A peptide according to claim 1 wherein the peptide is N-phenoxyacetyl-L-leucyl-(3S,4S)-statyl-L-leucyl-L-phenylalanine, or the amide or C 1-4 alkyl ester form thereof.
Claim 5
Dependent Claim
21 words
A peptide according to claim 1 wherein the peptide is N-phenoxyacetyl-L-leucyl-4(S)-amino-3(S)-hydroxy-5-phenylpentanoyl-L-leucyl-L-phenylalanine, or the amide or C 1-4 alkyl ester form thereof.
Claim 6
Dependent Claim
21 words
A peptide according to claim 1 wherein the peptide is L-leucyl-(3S,4S)-statyl-L-valyl-L-phenylalanine, or the amide or C 1-4 alkyl ester form thereof.
Claim 7
Dependent Claim
21 words
A peptide according to claim 1 wherein the peptide is L-leucyl-(3S,4S)-statyl-L-leucyl-L-phenylalanine, or the amide or C 1-4 alkyl ester form thereof.
Claim 8
Dependent Claim
21 words
A peptide according to claim 1 wherein the peptide is L-leucyl-4(S)-amino-3(S)-hydroxy-5-phenylpentanoyl-L-leucyl-L-phenylalanine, or the amide or C 1-4 alkyl ester form thereof.
Claim 9
Dependent Claim
112 words
A pharmaceutical composition for treating renin-associated hypertension, comprising a pharmaceutical carrier and a therapeutically effective amount of a peptide of the formula: ##STR8## wherein: A is hydrogen; or phenoxyacetyl; R 1 is C 3-6 straight or branched alkyl; C 3-7 cycloalkyl; phenyl; or phenyl monosubstituted with hydroxyl, fluoro, chloro, bromo, methyl, or trifluoromethyl; R 2 is hydrogen; or methyl; R 3 is methyl; or isopropyl; R 4 is phenyl; or 4-hydroxyphenyl; and B is OR; NHR; or NR 2 , where each R may be the same or different and is hydrogen or C 1-4 alkyl; and a pharmaceutically acceptable salt thereof; all of the asymmetric carbon atoms having an S configuration.
Claim 10
Dependent Claim
112 words
A pharmaceutical composition for treating renin-associated hypertension, comprising a pharmaceutical carrier and a therapeutically effective amount of a peptide of the formula: ##STR8## wherein: A is hydrogen; or phenoxyacetyl; R 1 is C 3-6 straight or branched alkyl; C 3-7 cycloalkyl; phenyl; or phenyl monosubstituted with hydroxyl, fluoro, chloro, bromo, methyl, or trifluoromethyl; R 2 is hydrogen; or methyl; R 3 is methyl; or isopropyl; R 4 is phenyl; or 4-hydroxyphenyl; and B is OR; NHR; or NR 2 , where each R may be the same or different and is hydrogen or C 1-4 alkyl; and a pharmaceutically acceptable salt thereof; all of the asymmetric carbon atoms having an S configuration.
Claim 11
Dependent Claim
22 words
A pharmaceutical composition according to claim 8 wherein the peptide is N-phenoxyacetyl-L-leucyl-4(S)-amino-3(S)-hydroxy-5-phenylpentanoyl-L-leucyl-L-phenylalanine, or the amide or C 1-4 alkyl ester form thereof.
Claim 12
Independent Claim
116 words
A method of treating renin-associated hypertension comprising administering to a patient in need of such treatment, a therapeutically effective amount of a peptide of the formula: ##STR9## wherein: A is hydrogen; or phenoxyacetyl; R 1 is C 3-6 straight or branched alkyl; C 3-7 cycloalkyl; phenyl; or phenyl monosubstituted with hydroxyl, fluoro, chloro, bromo, methyl, or trifluoromethyl; R 2 is hydrogen; or methyl; R 3 is methyl; or isopropyl; R 4 is phenyl; or 4-hydroxyphenyl; and B is OR; NHR; or NR 2 , where each R may be the same or different and is hydrogen or C 1-4 alkyl; and a pharmaceutically acceptable salt thereof; all of the asymmetric carbon atoms having an S configuration.
Claim 13
Independent Claim
116 words
A method of treating renin-associated hypertension comprising administering to a patient in need of such treatment, a therapeutically effective amount of a peptide of the formula: ##STR9## wherein: A is hydrogen; or phenoxyacetyl; R 1 is C 3-6 straight or branched alkyl; C 3-7 cycloalkyl; phenyl; or phenyl monosubstituted with hydroxyl, fluoro, chloro, bromo, methyl, or trifluoromethyl; R 2 is hydrogen; or methyl; R 3 is methyl; or isopropyl; R 4 is phenyl; or 4-hydroxyphenyl; and B is OR; NHR; or NR 2 , where each R may be the same or different and is hydrogen or C 1-4 alkyl; and a pharmaceutically acceptable salt thereof; all of the asymmetric carbon atoms having an S configuration.
Claim 14
Dependent Claim
21 words
A method according to claim 10 wherein the peptide is N-phenoxyacetyl-L-leucyl-4(S)-amino-3(S)-hydroxy-5-phenylpentanoyl-L-leucyl-L-phenylalanine, or the amide or C 1-4 alkyl ester form thereof.
Claim 15
Dependent Claim
112 words
A pharmaceutical composition for treating renin-associated hyperaldosteronism, comprising a pharmaceutical carrier and a therapeutically effective amount of a peptide of the formula: ##STR10## wherein: A is hydrogen; or phenoxyacetyl; R 1 is C 3-6 straight or branched alkyl; C 3-7 cycloalkyl; phenyl; or phenyl monosubstituted with hydroxyl, fluoro, chloro, bromo, methyl, or trifluoromethyl; R 2 is hydrogen; or methyl; R 3 is methyl; or isopropyl; R 4 is phenyl; or 4-hydroxyphenyl; and B is OR; NHR; or NR 2 , where each R may be the same or different and is hydrogen or C 1-4 alkyl; and a pharmaceutically acceptable salt thereof; all of the asymmetric carbon atoms having an S configuration.
Claim 16
Dependent Claim
112 words
A pharmaceutical composition for treating renin-associated hyperaldosteronism, comprising a pharmaceutical carrier and a therapeutically effective amount of a peptide of the formula: ##STR10## wherein: A is hydrogen; or phenoxyacetyl; R 1 is C 3-6 straight or branched alkyl; C 3-7 cycloalkyl; phenyl; or phenyl monosubstituted with hydroxyl, fluoro, chloro, bromo, methyl, or trifluoromethyl; R 2 is hydrogen; or methyl; R 3 is methyl; or isopropyl; R 4 is phenyl; or 4-hydroxyphenyl; and B is OR; NHR; or NR 2 , where each R may be the same or different and is hydrogen or C 1-4 alkyl; and a pharmaceutically acceptable salt thereof; all of the asymmetric carbon atoms having an S configuration.
Claim 17
Dependent Claim
22 words
A pharmaceutical composition according to claim 12 wherein the peptide is N-phenoxyacetyl-L-leucyl-4(S)-amino-3(S)-hydroxy-5-phenylpentanoyl-L-leucyl-L-phenylalanine, or the amide or C 1-4 alkyl ester form thereof.
Claim 18
Independent Claim
116 words
A method of treating renin-associated hyperaldosteronism, comprising administering to a patient in need of such treatment, a therapeutically effective amount of a peptide of the formula: ##STR11## wherein: A is hydrogen; or phenoxyacetyl; R 1 is C 3-6 straight or branched alkyl; C 3-7 cycloalkyl; phenyl; or phenyl monosubstituted with hydroxyl, fluoro, chloro, bromo, methyl, or trifluoromethyl; R 2 is hydrogen; or methyl; R 3 is methyl; or isopropyl; R 4 is phenyl; or 4-hydroxyphenyl; and B is OR; NHR; or NR 2 , where each R may be the same or different and is hydrogen or C 1-4 alkyl; and a pharmaceutically acceptable salt thereof; all of the asymmetric carbon atoms having an S configuration.
Claim 19
Independent Claim
116 words
A method of treating renin-associated hyperaldosteronism, comprising administering to a patient in need of such treatment, a therapeutically effective amount of a peptide of the formula: ##STR11## wherein: A is hydrogen; or phenoxyacetyl; R 1 is C 3-6 straight or branched alkyl; C 3-7 cycloalkyl; phenyl; or phenyl monosubstituted with hydroxyl, fluoro, chloro, bromo, methyl, or trifluoromethyl; R 2 is hydrogen; or methyl; R 3 is methyl; or isopropyl; R 4 is phenyl; or 4-hydroxyphenyl; and B is OR; NHR; or NR 2 , where each R may be the same or different and is hydrogen or C 1-4 alkyl; and a pharmaceutically acceptable salt thereof; all of the asymmetric carbon atoms having an S configuration.
Claim 20
Dependent Claim
21 words
A method according to claim 14 wherein the peptide is N-phenoxyacetyl-L-leucyl-4(S)-amino-3(S)-hydroxy-5-phenylpentanoyl-L-leucyl-L-phenylalanine, or the amide or C 1-4 alkyl ester form thereof.
Claim 21
Independent Claim
131 words
A method of determining the presence of renin-associated hypertension in a patient, comprising administering to such a patient, at a hypotensive dosage level and as a single dose, a peptide of the formula: ##STR12## wherein: A is hydrogen; or phenoxyacetyl; R 1 is C 3-6 straight or branched alkyl; C 3-7 cycloalkyl; phenyl; or phenyl monosubstituted with hydroxyl, fluoro, chloro, bromo, methyl, or trifluoromethyl; R 2 is hydrogen; or methyl; R 3 is methyl; or isopropyl; R 4 is phenyl; or 4-hydroxyphenyl; and B is OR; NHR; or NR 2 , where each R may be the same or different and is hydrogen or C 1-4 alkyl; and a pharmaceutically acceptable salt thereof; all of the asymmetric carbon atoms having an S configuration; followed by monitoring of said patient's blood pressure.
Claim 22
Independent Claim
131 words
A method of determining the presence of renin-associated hypertension in a patient, comprising administering to such a patient, at a hypotensive dosage level and as a single dose, a peptide of the formula: ##STR12## wherein: A is hydrogen; or phenoxyacetyl; R 1 is C 3-6 straight or branched alkyl; C 3-7 cycloalkyl; phenyl; or phenyl monosubstituted with hydroxyl, fluoro, chloro, bromo, methyl, or trifluoromethyl; R 2 is hydrogen; or methyl; R 3 is methyl; or isopropyl; R 4 is phenyl; or 4-hydroxyphenyl; and B is OR; NHR; or NR 2 , where each R may be the same or different and is hydrogen or C 1-4 alkyl; and a pharmaceutically acceptable salt thereof; all of the asymmetric carbon atoms having an S configuration; followed by monitoring of said patient's blood pressure.
References Cited (Backward Citations)
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1986-05-23 | 1986-11-22 | 1987-05-24 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1990-05-23 | 1990-11-22 | 1991-05-24 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1994-05-23 | 1994-11-22 | 1995-05-24 | $7700.00 | Window Closed / Lapsed |