Sterol/stanol nitroderivatives and use thereof
Sterol and stanol nitro derivatives and their use in treating or preventing cardiovascular disease, its underlying conditions and other disorders are disclosed. The disclosed nitro derivatives are synthesized by ester linkage of a nitric oxide (NO)-releasing moiety to a sterol or stanol compound.
1. Sterol and/or stanol nitroderivatives, including pharmaceutically acceptable salts and stereoisomers thereof, represented by the general formulae:
wherein in the foregoing formulae, R is selected from CH 3 and CH 2 CH 3 and R 1 is an aromatic or aliphatic NO releasing agent selected from the group consisting of:
wherein n is an integer from 1 to 20.
2. The nitroderivatives of claim 1 wherein the sterol and stanol are selected from the group consisting of sitosterol, campesterol, stigmasterol, brassicasterol, desmosterol, chalinosterol, poriferasterol, clionasterol, sitostanol, campestanol, stigmastanol, brassicastanol, desmostanol, chalinostanol, poriferastanol, and clionastanol.
3. Pharmaceutical compositions comprising the sterol and/or stanol nitroderivatives of claim 1 and one or more suitable carriers, excipients or adjuvants.
4. The sterol/stanol nitroderivatives of claim 1 wherein the sterol and stanol are in either a natural or synthesized form.
5. The sterol/stanol nitroderivatives of claim 1 wherein the sterol and stanol are in any one of their isomeric forms.
6. The sterol/stanol nitroderivatives of claim 1 wherein the sterol/stanol is selected from the group consisting of sitostanol, sitosterol, campestnaol and campesterol.
7. Pharmaceutical compositions comprising the sterol/stanol nitroderivatives of claim 1 and at least one agent which reduces cholesterol synthesis in humans.
8. The pharmaceutical compositions of claim 7 wherein the agent is a 3-hydroxy-3-methyl glutaryl coenzyme-A (HMG-CoA) reductase inhibitor.
9. Pharmaceutical compositions comprising the sterol/stanol nitroderivatives of claim 1 and one or more of the following: ACE inhibitors, angiotensin II receptor antagonists, beta-andrenergic blockers, calcium channel blockers, and anti-thrombotics.
10. The pharmaceutical compositions of claim 9 , wherein the anti-thrombotics are selected from aspirin, nitrosated ACE inhibitors, nitrosated angiotensin II receptor antogonists, nitrosated beta-andrenergic blockers, and nitrosated aspirin.