Nitrosated And Nitrosylated Cardiovascular Compounds, Compositions And Methods Of Use

Abstract

The invention describes novel nitrosated and / or nitrosylated cardiovascular compounds or pharmaceutically acceptable salts thereof, and novel compositions comprising at least one nitrosated and / or nitrosylated cardiovascular compound, and, optionally, at least one nitric oxide donor and / or at least one therapeutic agent. The invention also provides novel compositions and kits comprising at least one cardiovascular compound of the invention, that is optionally nitrosated and / or nitrosylated, and, optionally, at least one nitric oxide donor compound and / or at least one therapeutic agent. The invention also provides methods for (a) treating cardiovascular diseases; (b) treating renovascular diseases; (c) treating diabetes; (d) treating diseases resulting from oxidative stress; (e) treating endothelial dysfunctions; (f) treating diseases caused by endothelial dysfunctions; (g) treating cirrhosis; (h) treating pre-eclampsia; (j) treating osteoporosis; and (k) treating nephropathy. The nitrosated and / or nitrosylated cardiovascular compounds are preferably nitrosated and / or nitrosylated aldosterone antagonists, nitrosated and / or nitrosylated angiotensin II antagonists, nitrosated and / or nitrosylated calcium channel blockers, nitrosated and / or nitrosylated endothelin antagonists, nitrosated and / or nitrosylated hydralazine compounds, nitrosated and / or nitrosylated neutral endopeptidase inhibitors and nitrosated and / or nitrosylated renin inhibitors.

Description

RELATED APPLICATIONS [0001] This application claims priority under 35 USC § 119 to U.S. Application No. 60 / 498,309 filed Aug. 28, 2003, and to U.S. Application No. 60 / 535,542 filed Jan. 12, 2004.FIELD OF THE INVENTION [0002] The invention describes novel nitrosated and / or nitrosylated cardiovascular compounds or pharmaceutically acceptable salts thereof, and novel compositions comprising at least one nitrosated and / or nitrosylated cardiovascular compound, and, optionally, at least one nitric oxide donor and / or at least one therapeutic agent. The invention also provides novel compositions and kits comprising at least one cardiovascular compound of the invention, that is optionally nitrosated and / or nitrosylated, and, optionally, at least one nitric oxide donor compound and / or at least one therapeutic agent. The invention also provides methods for (a) treating cardiovascular diseases; (b) treating renovascular diseases; (c) treating diabetes; (d) treating diseases resulting from oxida...

AI Technical Summary

Benefits of technology

[0006] The invention is also based on the discovery that administering at least one cardiovascular compound or a pharmaceutically acceptable salt thereof, that is optionally substituted with at least one NO and / or NO2 group (i.e., nitrosylated and / or nitrosated), and, optionally, at least one nitric oxide donor improves the properties of the cardiovascular compound. Nitric oxide donors include, for example, S-nitrosothiols, nitrites, nitrates, N-oxo-N-nitrosamines, furoxans, sydnonimines, SPM 3672, SPM 5185, SPM 5186 and analogues thereof, and substrates of the various isozymes of nitric oxide synthase. Thus, another embodiment of the invention provides compositions comprising at least one cardiovascular compound that is optionally substituted with at least one NO and / or NO2 group (i.e., nitrosylated and / or nitrosated), and at least one nitric oxide donor compound. The invention also provides for such compositions in a pharmaceutically acceptable carrier.

Problems solved by technology

The compounds administered for the treatment of diuresis, cardiovascular diseases, and diseases resulting from oxidative and / or endothelial dysfunctions often result in toxic, chronic and / or debilitating side effects.

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