Methods and formulations for modulating lyn kinase activity and treating related disorders
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) a compound of formula:
or a pharmaceutically acceptable salt thereof; and
b) a therapeutic agent chosen from:
i) metformin;
ii) insulin;
iii) a PPAR agonist;
iv) an insulin secretagogue;
v) a sulfonylurea-based drug; and
vi) an α-glucosidase inhibitor.
2. The pharmaceutical composition of claim 1 wherein:
the PPAR agonist is chosen from troglitazone, pioglitazone, rosiglitazone, ciglitazone, 5-((4-(2-(methyl-2-pyridinylamino)ethoxy)phenyl)methyl)-2,4-thiazolidinedione, AD 5075, WAY-120,744, englitazone, darglitazone, gemfibrozil, fenofibrate, clofibrate, and ciprofibrate;
the insulin secretagogue is chosen from forskolin, dibutryl cAMP, and isobutylmethylxanthine;
the sulfonylurea-based drug is chosen from glisoxepid, glyburide, acetohexamide, chlorpropamide, glibornuride, tolbutamide, tolazamide, glipizide, gliclazide, gliquidone, glyhexamide, phenbutamide, and tolcyclamide; and
the α-glucosidase inhibitor is chosen from acarbose and miglitol.
3. The pharmaceutical composition of claim 1 wherein the PPAR agonist is pioglitazone or rosiglitazone.
4. The pharmaceutical composition of claim 1 which is in unit dosage form.
5. The pharmaceutical composition of claim 4 wherein the unit dosage form is in the form of a solution, suspension, emulsion, tablet, pill, pellet, capsule, powder, sustained-release formulation, controlled-release formulation, suppository, aerosol, or spray.
6. The pharmaceutical composition of claim 5 wherein the unit dosage form is in the form of a solution, suspension, tablet, capsule, sustained-release formulation, or controlled-release formulation.
7. The pharmaceutical composition of claim 4 wherein the unit dosage form is in the form of tablet, lozenge, aqueous or oily suspension, granule, powder, emulsion, capsule, syrup, or elixir.
8. The pharmaceutical composition of claim 7 wherein the unit dosage form is in the form of tablet, lozenge, aqueous or oily suspension, or capsule.
9. The pharmaceutical composition of claim 4 further comprising a sweetening agent, a flavoring agent, a coloring agent, or a preserving agent.
10. The pharmaceutical composition of claim 4 wherein the composition is in the form of a coated tablet.
11. The pharmaceutical composition of claim 1 wherein the therapeutic agent is metformin.
12. The pharmaceutical composition of claim 1 wherein the therapeutic agent is insulin.
13. The pharmaceutical composition of claim 1 wherein the therapeutic agent is a PPAR agonist.
14. The pharmaceutical composition of claim 13 wherein the PPAR agonist is chosen from troglitazone, pioglitazone, rosiglitazone, ciglitazone, 5-((4-(2-(methyl-2-pyridinylamino)ethoxy)phenyl)methyl)-2,4-thiazolidinedione, AD 5075, WAY-120,744, englitazone, darglitazone, gemfibrozil, fenofibrate, clofibrate, and ciprofibrate.
15. The pharmaceutical composition of claim 1 wherein the therapeutic agent is an insulin secretagogue.
16. The pharmaceutical composition of claim 15 wherein the insulin secretagogue is chosen from forskolin, dibutryl cAMP, and isobutylmethylxanthine.
17. The pharmaceutical composition of claim 1 wherein the therapeutic agent is a sulfonylurea-based drug.
18. The pharmaceutical composition of claim 17 wherein the sulfonylurea-based drug is chosen from glisoxepid, glyburide, acetohexamide, chlorpropamide, glibornuride, tolbutamide, tolazamide, glipizide, gliclazide, gliquidone, glyhexamide, phenbutamide, and tolcyclamide.
19. The pharmaceutical composition of claim 1 wherein the therapeutic agent is an α-glucosidase inhibitor.
20. The pharmaceutical composition of claim 19 wherein the α-glucosidase inhibitor is acarbose or miglitol.