US5155137A
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Complexes of nitric oxide with polyamines
Assignee: United States Department of Health and Human Services
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Filing: 1990-09-20
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Granted: 1992-10-13
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Expires: 2010-09-20
Abstract
Abstract There are disclosed novel complexes of nitric oxide and polyamines which are useful in treating cardiovascular disorders, including hypertension. The disclosed compounds release nitric oxide (endothelium-derived relaxing factor) under physiological conditions in a sustained and controllable fashion, and possess long mechanisms of action.
Inventors
- 👤 Larry K. Keefer
- 👤 Joseph A. Hrabie
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-29 05:08
CPC Classifications
C; C07; C07C; C07C243/00; C07C243/04; C07C243/06; A; A61; A61P; A61P9/00; A61P9/08; A61P9/10; A61P9/12; C01; C01B; C01B21/00; C01B21/20; C01B21/24; C07C211/00; C07C211/01; C07C211/02; C07C211/14
Claims Analysis
Total Claims: 20
Claim 1
Independent Claim
102 words
A compound of Formula I: ##STR9## wherein: d and b, same or different, are zero or one; R 1 , R 2 , R 3 , R 4 , and R 5 , same or different, are hydrogen, C 3-8 cycloalkyl, C 1-12 straight or branched chain alkyl, benzyl, benzoyl, phthaloyl, acetyl, trifluoroacetyl, p-toluyl, t-butoxycarbonyl or 2,2,2-trichloro-t-butoxycarbonyl; and x, y and z, same or different, are 2 to 12; or a pharmaceutically acceptable salt thereof; with the proviso that R 1 and R 3 are not both methyl, when R 2 is hydrogen, x is 2, and b and d are zero.
Claim 2
Dependent Claim
102 words
A compound of Formula I: ##STR9## wherein: d and b, same or different, are zero or one; R 1 , R 2 , R 3 , R 4 , and R 5 , same or different, are hydrogen, C 3-8 cycloalkyl, C 1-12 straight or branched chain alkyl, benzyl, benzoyl, phthaloyl, acetyl, trifluoroacetyl, p-toluyl, t-butoxycarbonyl or 2,2,2-trichloro-t-butoxycarbonyl; and x, y and z, same or different, are 2 to 12; or a pharmaceutically acceptable salt thereof; with the proviso that R 1 and R 3 are not both methyl, when R 2 is hydrogen, x is 2, and b and d are zero.
Claim 3
Dependent Claim
41 words
A compound as recited in claim 1, wherein: R 1 , R 2 , R 3 , R 4 and R 5 , same or different, are hydrogen, C 5-6 cycloalkyl, C 1-4 straight or branched chain alkyl, benzyl or acetyl.
Claim 4
Dependent Claim
45 words
A compound as recited in claim 2, wherein: R 1 , R 2 , R 3 , R 4 and R 5 , same or different, are hydrogen, methyl, ethyl, benzyl or acetyl; and x, y and z, same or different, are 2 to 4.
Claim 5
Dependent Claim
32 words
A compound as recited in claim 3, wherein: R 1 , R 2 , R 3 , R 4 and R 5 , same or different, are hydrogen, methyl, benzyl, or acetyl.
Claim 6
Dependent Claim
106 words
A compound as recited in claim 1, wherein the compound is: CH 3 --NH 2 + --(CH 2 ) 4 --N(--N 2 O 2 - )(--CH 3 ), H 3 N + --(CH 2 ) 3 --NH--(CH 2 ) 4 --N--(--N 2 O 2 - )[--(CH 2 ) 3 NH 2 ] or a tautomer thereof, H 3 N + --(CH 2 ) 3 --N(--N 2 O 2 - )[--(CH 2 ) 2 --CH 3 ], H 3 N + --(CH 2 ) 3 --N(--N 2 O 2 - )[--(CH 2 ) 4 NH 2 ] or a tautomer thereof; or a pharmaceutically acceptable salt thereof.
Claim 7
Independent Claim
100 words
A method of treating cardiovascular disorders which are treatable by lowering blood pressure, which method comprises: administering to a mammal, in need thereof, an effective amount of a compound of Formula I: ##STR10## wherein: b and d, same or different, are zero or one; R 1 , R 2 , R 3 , R 4 and R 5 , same or different, are hydrogen, C 3-8 cycloalkyl, C 1-12 straight or branched chain alkyl, benzyl, benzoyl, phthaloyl, acetyl, trifluoroacetyl, p-toluyl, t-butoxycarbonyl or 2,2,2-trichloro-t-butoxycarbonyl; x, y and z, same or different, are 2 to 12; or a pharmaceutically acceptable salt thereof.
Claim 8
Independent Claim
100 words
A method of treating cardiovascular disorders which are treatable by lowering blood pressure, which method comprises: administering to a mammal, in need thereof, an effective amount of a compound of Formula I: ##STR10## wherein: b and d, same or different, are zero or one; R 1 , R 2 , R 3 , R 4 and R 5 , same or different, are hydrogen, C 3-8 cycloalkyl, C 1-12 straight or branched chain alkyl, benzyl, benzoyl, phthaloyl, acetyl, trifluoroacetyl, p-toluyl, t-butoxycarbonyl or 2,2,2-trichloro-t-butoxycarbonyl; x, y and z, same or different, are 2 to 12; or a pharmaceutically acceptable salt thereof.
Claim 9
Dependent Claim
45 words
A method of treating cardiovascular disorders as recited in claim 6, wherein: R 1 , R 2 , R 3 , R 4 and R 5 , same or different, are hydrogen, C 5-6 cycloalkyl, C 1-4 straight or branched chain alkyl, benzyl or acetyl.
Claim 10
Dependent Claim
49 words
A method of treating cardiovascular disorders as recited in claim 6, wherein: R 1 , R 2 , R 3 , R 4 and R 5 , same or different, are hydrogen, methyl, ethyl, benzyl or acetyl; and x, y and z, same or different, are 2 to 4.
Claim 11
Dependent Claim
35 words
A method of treating cardiovascular disorders as recited in claim 6, wherein: R 1 , R 2 , R 3 , R 4 and R 5 , same or different, are hydrogen, methyl or acetyl.
Claim 12
Independent Claim
108 words
A method of treating cardiovascular disorders, wherein the Formula I compound administered is: CH 3 --NH 2 + --(CH 2 ) 4 --N(--N 2 O 2 - )(--CH 3 ), H 3 N + --(CH 2 ) 3 --NH--(CH 2 ) 4 --N--(--N 2 O 2 - )[--(CH 2 ) 3 NH 2 ] or a tautomer thereof, H 3 N + --(CH 2 ) 3 --N(--N 2 O 2 - )[--(CH 2 ) 2 --CH 3 ], H 3 N + --(CH 2 ) 3 --N(--N 2 O 2 - )[--(CH 2 ) 4 NH 2 ] or a tautomer thereof; or a pharmaceutically acceptable salt thereof.
Claim 13
Independent Claim
108 words
A method of treating cardiovascular disorders, wherein the Formula I compound administered is: CH 3 --NH 2 + --(CH 2 ) 4 --N(--N 2 O 2 - )(--CH 3 ), H 3 N + --(CH 2 ) 3 --NH--(CH 2 ) 4 --N--(--N 2 O 2 - )[--(CH 2 ) 3 NH 2 ] or a tautomer thereof, H 3 N + --(CH 2 ) 3 --N(--N 2 O 2 - )[--(CH 2 ) 2 --CH 3 ], H 3 N + --(CH 2 ) 3 --N(--N 2 O 2 - )[--(CH 2 ) 4 NH 2 ] or a tautomer thereof; or a pharmaceutically acceptable salt thereof.
Claim 14
Dependent Claim
26 words
The method of claim 6, wherein said cardiovascular disorder which is treated is selected from the group consisting of hypertension, arteriosclerosis, cerebral vasospasm and coronary vasospasm.
Claim 15
Dependent Claim
88 words
A pharmaceutical composition, comprising: an effective amount of a compound of Formula I: ##STR11## wherein: d and b, same or different, are zero or one, R 1 , R 2 , R 3 , R 4 and R 5 , same or different, are hydrogen, C 3-8 cycloalkyl, C 1-12 straight or branched chain alkyl, benzyl, benzoyl, phthaloyl, acetyl, trifluoroacetyl, p-toluyl, t-butoxycarbonyl or 2,2,2-trichloro-t-butoxycarbonyl, and x, y and z, same or different, are 2 to 12, or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable carrier therefor.
Claim 16
Dependent Claim
88 words
A pharmaceutical composition, comprising: an effective amount of a compound of Formula I: ##STR11## wherein: d and b, same or different, are zero or one, R 1 , R 2 , R 3 , R 4 and R 5 , same or different, are hydrogen, C 3-8 cycloalkyl, C 1-12 straight or branched chain alkyl, benzyl, benzoyl, phthaloyl, acetyl, trifluoroacetyl, p-toluyl, t-butoxycarbonyl or 2,2,2-trichloro-t-butoxycarbonyl, and x, y and z, same or different, are 2 to 12, or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable carrier therefor.
Claim 17
Dependent Claim
42 words
A pharmaceutical composition as recited in claim 12, wherein: R 1 , R 2 , R 3 , R 4 and R 5 , same or different, are hydrogen, C 5-6 cycloalkyl, C 1-4 straight or branched chain alkyl, benzyl or acetyl.
Claim 18
Dependent Claim
46 words
A pharmaceutical composition as recited in claim 13, wherein: R 1 , R 2 , R 3 , R 4 and R 5 , same or different, are hydrogen, methyl, ethyl, benzyl or acetyl; and x, y and z, same or different, are 2 to 4.
Claim 19
Dependent Claim
32 words
A pharmaceutical composition as recited in claim 14, wherein: R 1 , R 2 , R 3 , R 4 and R 5 , same or different, are hydrogen, methyl or acetyl.
Claim 20
Dependent Claim
108 words
A pharmaceutical composition as recited in claim 12, wherein the Formula I compound is: CH 3 --NH + --(CH 2 ) 4 --N(--N 2 O 2 - )(--CH 3 ), H 3 N + --(CH 2 ) 3 --NH--(CH 2 ) 4 --N--(--N 2 O 2 - )[--(CH 2 ) 3 NH 2 ] or a tautomer thereof, H 3 N + --(CH 2 ) 3 --N(--N 2 O 2 - )[--(CH 2 ) 2 --CH 3 ], H 3 N + --(CH 2 ) 3 --N(--N 2 O 2 - )[--(CH 2 ) 4 NH 2 ] or a tautomer thereof; or a pharmaceutically acceptable salt thereof.
References Cited (Backward Citations)
No citation records indexed.
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1995-10-13 | 1996-04-13 | 1996-10-13 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1999-10-13 | 2000-04-13 | 2000-10-13 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2003-10-13 | 2004-04-13 | 2004-10-13 | $7700.00 | Window Closed / Lapsed |