Methods and formulations for treating cardiovascular disease
Inventors
Reaume, Andrew G. • Saporito, Michael S.
Assignees
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Publication Number
US-9216959-B2
Publication Date
2015-12-22
Expiration Date
Abstract
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.
Core Innovation
The disclosed invention provides Lyn-kinase-modulating compounds usable as pharmaceutical composition components for treating and/or preventing disease. The compounds are described as compounds of Formulas I-VII and include pharmaceutically acceptable salts and prodrugs.
The disclosure addresses the need for therapeutic and/or prophylactic agents to treat and/or prevent cardiovascular and metabolic disorders, including metabolic syndrome (Syndrome X), dyslipidemia/dyslipoproteinemia, type II diabetes/diabetes, obesity, hypertension, renal disease, inflammation, and thrombotic disorders. The approach is presented as Lyn kinase-directed modulation for these conditions.
The disclosed rationale states that the compounds act as Lyn kinase activators/agonists, including up-regulating Lyn activity/expression. The disclosure also indicates that such Lyn modulation may involve the insulin receptor pathway, linking Lyn kinase activity to glucose metabolism and related metabolic outcomes.
Claims Coverage
The independent claim contains three core inventive aspects: a compound defined by a general formula with constrained substituents and integer parameters, the inclusion of a pharmaceutically acceptable salt thereof, and combination with a cardiovascular drug selected from a specified list.
Pharmaceutical composition with a Lyn-kinase-modulating compound of defined formula
A pharmaceutical composition comprising a compound of formula (as stated) or a pharmaceutically acceptable salt, wherein R1 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 with m being 0 or 1 such that m+n is less than or equal to 5.
Pharmaceutical composition including a selected cardiovascular drug
The pharmaceutical composition includes 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.
Refined cardiovascular drug selection to a centrally acting antihypertensive agent
The pharmaceutical composition wherein the centrally acting antihypertensive drug is methyldopa or methyldopa HCl.
Refined cardiovascular drug selection to an antihypertensive direct vasodilator
The pharmaceutical composition wherein the antihypertensive direct vasodilator is diazoxide or hydralazine HCl.
Refined cardiovascular drug selection by renin-angiotensin targeting
The pharmaceutical composition wherein the cardiovascular drug affects the renin-angiotensin system.
Overall, the claim coverage centers on a pharmaceutical composition that combines a specifically constrained compound-of-formula, or pharmaceutically acceptable salt, with a chosen cardiovascular drug from a defined set, with additional refinements narrowing the cardiovascular drug selection to centrally acting antihypertensives, direct vasodilators, or renin-angiotensin system-affecting drugs.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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