Complexes of nitric oxide with polyamines
AssigneeThe Government of the United States of America as represented by the Secretary of the Department of Health and Human Services
InventorsLarry K. Keefer, Joseph A. Hrabie
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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.
Claims13
A compound of Formula II:
- ##STR7## and R.sub.6 and R.sub.7, same or different, are hydrogen, C.sub.3-8 cycloalkyl, C.sub.1-12 straight or branched chain alkyl, benzyl, benzoyl, phthaloyl, acetyl, trifluoroacetyl, p-toluyl, t-butoxycarbonyl or 2,2,2-trichloro-t-butoxycarbonyl;
- f is 0 to 12, with the proviso that when B is the substituted piperazine moiety ##STR8## then f is 2 to 12;
- or a pharmaceutically acceptable salt thereof.
A compound of Formula III:
- ##STR9## wherein:
- R.sub.8 is hydrogen, C.sub.3-8 cycloalkyl, C.sub.1-12 straight or branched chain alkyl, benzyl, benzoyl, phthaloyl, acetyl, trifluoroacetyl, p-toluyl, t-butoxycarbonyl or 2,2,2-tri-chloro-t-butoxycarbonyl;
- R.sub.9 is hydrogen or a C.sub.1 -C.sub.12 straight or branched chain alkyl;
- and
- g is 2 to 6;
- or
- a pharmaceutically acceptable salt thereof.
A method of treating cardiovascular disorders which are treatable by lowering blood pressure, the method comprising:
- administering to a mammal, in need thereof, an effective amount of a compound of Formula II:
- ##STR11## R.sub.6 and R.sub.7, same or different, are hydrogen, C.sub.3-8 cycloalkyl, C.sub.1-12 straight or branched chain alkyl, benzyl, benzoyl, phthaloyl, acetyl, trifluoroacetyl, p-toluyl, t-butoxycarbonyl or 2,2,2-trichloro-t-butoxycarbonyl;
- f is 0 to 12, with the proviso that when B is the substituted piperazine moiety ##STR12## then f is 2 to 12;
- or a pharmaceutically acceptable salt thereof.
A method of treating cardiovascular disorders which are treatable by lowering blood pressure, the method comprising:
- administering to a mammal, in need thereof, an effective amount of a compound of Formula III:
- ##STR13## wherein:
- R.sub.8 is hydrogen, C.sub.3-8 cycloalkyl, C.sub.1-12 straight or branched chain alkyl, benzyl, benzoyl, phthaloyl, acetyl, trifluoroacetyl, p-toluyl, t-butoxycarbonyl or 2,2,2-trichloro-t-butoxycarbonyl;
- R.sub.9 is hydrogen or a C.sub.1 -C.sub.12 straight or branched chain alkyl;
- and
- g is 2 to 6;
- or
- a pharmaceutically acceptable salt thereof.
A pharmaceutical composition, comprising:
- an effective amount of a compound of Formula II for treating a cardiovascular disorder which is treatable by lowering blood pressure;
- ##STR14## R.sub.6 and R.sub.7, same or different, are hydrogen, C.sub.3-8 cycloalkyl, C.sub.1-12 straight or branched chain alkyl, benzyl, benzoyl, phthaloyl, acetyl, trifluoroacetyl, p-toluyl, t-butoxycarbonyl or 2,2,2-trichloro-t butoxycarbonyl,
- f is 0 to 12, with the proviso that when B is the substituted piperazine moiety ##STR15## then f is 2 to 12, or a pharmaceutically acceptable salt thereof;
- and
- a pharmaceutically acceptable carrier therefor.
A pharmaceutical composition, comprising:
- an effective amount of a compound of Formula III for treating a cardiovascular disorder that is treatable by lowering blood pressure:
- ##STR16## wherein:
- R.sub.8 is hydrogen, C.sub.3-8 cycloalkyl, C.sub.1-12 straight or branched chain alkyl, benzyl, benzoyl, phthaloyl, acetyl, trifluoroacetyl, p-toluyl, t-butoxycarbonyl or 2,2,2-trichloro-t-butoxycarbonyl,
- R.sub.9 is hydrogen or a Chd 1-C.sub.12 straight or branched chain alkyl, and
- g is 2 to 6, or
- a pharmaceutically acceptable salt thereof;
- and a pharmaceutically carrier therefor.
Dependencies are inferred from the claim text.