Methods and formulations for modulating Lyn kinase activity and treating related disorders
Inventors
Reaume, Andrew G. • Saporito, Michael S.
Assignees
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Publication Number
US-9763945-B2
Publication Date
2017-09-19
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 invention provides Lyn kinase-modulating compounds of Formulas I-VII, including specific embodiments described as activators/agonists of Lyn kinase. The compounds act in an insulin-receptor pathway and modulate lipid metabolism in a mammal, with effects on insulin/glucose regulation together with blood lipid markers.
The disclosed subject matter addresses dyslipidemia and altered lipid metabolism in a mammal, including dyslipoproteinemia and metabolic syndrome (Syndrome X). It also targets metabolic and cardiovascular-related disorders in which lipid metabolism is implicated, including type II diabetes, obesity, fat-depot-associated conditions, and cardiovascular disease.
The disclosure further places the Lyn kinase-modulating compounds within therapeutic contexts that include inflammation- and thrombotic-related disorders and other conditions described for treatment or prophylaxis. It also provides treatment methods that include administering an effective amount of a composition comprising a compound of the defined formula, or a pharmaceutically acceptable salt, including specified administration routes and combination-therapy contexts with other therapeutic agents.
Claims Coverage
The independent claim covers a method for treating dyslipidemia or altering lipid metabolism by administering an effective amount of a Lyn kinase-modulating compound, or a pharmaceutically acceptable salt, defined by a constrained chemical formula. Across the independent-claim family, the claims refine the covered methods with specific constraints on lipid-metabolism aspects, administration routes, dosing ranges, and concurrent combination-therapy agent classes.
Formula-defined Lyn kinase-modulating compound for dyslipidemia treatment
A method of treating dyslipidemia or altering lipid metabolism in a mammal comprising administering to the mammal in need thereof an effective amount of a composition comprising a compound of formula, or a pharmaceutically acceptable salt thereof, wherein R1 is methyl and n is 1; X is a halogen; and m is 0 or 1.
Claim coverage centers on administering a composition containing a formula-defined compound, or pharmaceutically acceptable salt, to treat dyslipidemia or alter lipid metabolism, with dependent limitations specifying blood lipid markers, route-dependent dosing ranges, and concurrent administration with specified therapeutic-agent classes and example drugs.
Stated Advantages
Improves insulin/glucose regulation and lipid metabolism.
Treats dyslipidemia or alters lipid metabolism in a mammal.
Provides therapeutic or prophylactic utility for Lyn-kinase-associated disorders including dyslipidemia/metabolic syndrome (Syndrome X) and type II diabetes.
Documented Applications
Treating dyslipidemia or altering lipid metabolism in a mammal.
Altering metabolic syndrome (Syndrome X) and dyslipidemia/dyslipoproteinemia, including effects associated with blood lipid markers (HDL, LDL, VLDL, triglyceride, Lp(a), apo A-I, apo E, and related non-esterified fatty acids).
Addressing type II diabetes and insulin/glucose regulation, with illustrative in vivo indications described using oral glucose tolerance and blood glucose reductions.
Addressing obesity and fat-depot-related outcomes, with illustrative readouts described including weight gain and fat-pad weights and leptin levels.
Therapeutic or prophylactic treatment of cardiovascular diseases.
Therapeutic or prophylactic treatment of inflammation/thrombotic disorders.
Therapeutic or prophylactic treatment of renal disease.
Therapeutic or prophylactic treatment contexts described as involving combination therapy with agent classes including statins, PPAR agonists, bile-acid binding resins, niacin/RXR agonists, anti-obesity drugs, hormones/insulin/insulin secretagogues, α-glucosidase inhibitors, apo A-I agonists, cardiovascular drugs, and chemotherapeutic agents.
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