Methods and formulations for treating cardiovascular disease
View Patent ↗The present invention relates to compounds and pharmaceutically acceptable salts thereof and formulations comprising the compounds or a pharmaceutically acceptable salts thereof that are useful in modulating lyn kinase activity. In particular, the compounds or a pharmaceutically acceptable salts thereof are useful for treating or preventing a disease or disorder including cardiovascular disease, dyslipidemia, dyslipoproteinemia, a disorder of glucose metabolism, metabolic syndrome (i.e., Syndrome X), a peroxisome proliferator activated receptor-associated disorder, septicemia, a thrombotic disorder, type II diabetes, obesity, pancreatitis, hypertension, renal disease, inflammation, or impotence.
1. A pharmaceutical composition comprising a compound of formula:
or a pharmaceutically acceptable salt thereof,
wherein:
R 1 is an alkyl group;
X is a halogen;
Y is O, S, or NH;
Z is O or S; and
n is an integer from 0 to 5 and m is 0 or 1, wherein m+n is less than or equal to 5; and
a cardiovascular drug chosen from a peripheral anti-adrenergic drug, a centrally acting antihypertensive drug, an antihypertensive direct vasodilator, a drug affecting renin-angiotensin system, a peripheral vasodilator, an antianginal drug, a cardiac glycoside, an inodilator, an antidysrhythmic drug, a calcium entry blocker, ranitine, bosentan, rezulin, and phentolamine.
2. The pharmaceutical composition of claim 1 , wherein:
the compound is
and
the cardiovascular drug is chosen from a peripheral anti-adrenergic drug, a centrally acting antihypertensive drug, an antihypertensive direct vasodilator, a drug affecting renin-angiotensin system, a peripheral vasodilator, phentolamine, an antianginal drug, a cardiac glycoside, an inodilators, an antidysrhythmic drug, a calcium entry blocker, ranitine, bosentan, and rezulin.
3. The pharmaceutical composition of claim 1 , wherein the compound is a compound of formula
wherein:
R 1 is an alkyl group;
X is a halogen; and
n is an integer from 0 to 5 and m is 0 or 1, wherein m+n is less than or equal to 5.
4. The pharmaceutical composition of claim 1 , wherein the compound is a compound of formula
wherein:
R 1 is an alkyl group; and
n is an integer from 0 to 5.
5. The pharmaceutical composition of claim 1 , wherein the compound is a compound of formula
6. The pharmaceutical composition of claim 1 , wherein the compound is a compound of formula
wherein:
X is a halogen; and
m is an integer from 0 to 1.
7. The pharmaceutical composition of claim 1 , wherein the compound is a compound of formula
8. The pharmaceutical composition of claim 1 , wherein the cardiovascular drug is a peripheral anti-adrenergic drug.
9. The pharmaceutical composition of claim 1 , wherein the cardiovascular drug is a centrally acting antihypertensive drug.
10. The pharmaceutical composition of claim 9 , wherein the centrally acting antihypertensive drug is methyldopa or methyldopa HCl.
11. The pharmaceutical composition of claim 1 , wherein the cardiovascular drug is an antihypertensive direct vasodilator.
12. The pharmaceutical composition of claim 11 , wherein the antihypertensive direct vasodilator is diazoxide or hydralazine HCl.
13. The pharmaceutical composition of claim 1 , wherein the cardiovascular drug is a drug affecting renin-angiotensin system.
14. The pharmaceutical composition of claim 1 , wherein the cardiovascular drug is a peripheral vasodilator.
15. The pharmaceutical composition of claim 1 , wherein the cardiovascular drug is an antianginal drug.
16. The pharmaceutical composition of claim 1 , wherein the cardiovascular drug is a cardiac glycoside.
17. The pharmaceutical composition of claim 1 , wherein the cardiovascular drug is an inodilator.
18. The pharmaceutical composition of claim 17 , wherein the inodilator is chosen from amrinone, milrinone, enoximone, fenoximone, imazodan, and sulmazole.
19. The pharmaceutical composition of claim 1 , wherein the cardiovascular drug is an antidysrhythmic drug.
20. The pharmaceutical composition of claim 1 , wherein the cardiovascular drug is a calcium entry blocker.
21. The pharmaceutical composition of claim 1 , wherein the cardiovascular drug is ranitine, bosentan, rezulin, or phentolamine.