Complexes of nitric oxide with polyamines
AssigneeThe United States of America, as represented by the Secretary, 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.
Claims16
A compound of Formula I:
- ##STR9## wherein:
- d and b, same or different, are zero or one;
- R.sub.1, R.sub.2, R.sub.3, R.sub.4, and R.sub.5, 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;
- and
- x, y and z, same or different, are 2 to 12;
- or
- a pharmaceutically acceptable salt thereof;
- with the proviso that R.sub.1 and R.sub.3 are not both methyl, when R.sub.2 is hydrogen, x is 2, and b and d are zero.
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.sub.1, R.sub.2, R.sub.3, R.sub.4 and R.sub.5, 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;
- x, y and z, same or different, are 2 to 12;
- or
- a pharmaceutically acceptable salt thereof.
A method of treating cardiovascular disorders, wherein the Formula I compound administered is:
- CH.sub.3 --NH.sub.2.sup.+ --(CH.sub.2).sub.4 --N(--N.sub.2 O.sub.2.sup.-)(--CH.sub.3),
- H.sub.3 N.sup.+ --(CH.sub.2).sub.3 --NH--(CH.sub.2).sub.4 --N--(--N.sub.2 O.sub.2.sup.-)[--(CH.sub.2).sub.3 NH.sub.2 ] or a tautomer thereof,
- H.sub.3 N.sup.+ --(CH.sub.2).sub.3 --N(--N.sub.2 O.sub.2.sup.-)[--(CH.sub.2).sub.2 --CH.sub.3 ],
- H.sub.3 N.sup.+ --(CH.sub.2).sub.3 --N(--N.sub.2 O.sub.2.sup.-)[--(CH.sub.2).sub.4 NH.sub.2 ] or a tautomer thereof;
- or a pharmaceutically acceptable salt thereof.
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.sub.1, R.sub.2, R.sub.3, R.sub.4 and R.sub.5, 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, and
- x, y and z, same or different, are 2 to 12, or a pharmaceutically acceptable salt thereof;
- and a pharmaceutically acceptable carrier therefor.
Dependencies are inferred from the claim text.