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-10251883-B2
Publication Date
2019-04-09
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 relates to compounds that modulate Lyn activity and are described as surprisingly acting as Lyn activators/agonists, producing insulin-receptor-pathway-like effects. The compounds are formulated as pharmaceutically acceptable salts and prodrugs and are provided as compositions comprising compounds of Formulas I-VII.
The document describes examples of such compounds, including Compound 102 and Compound 105. The invention further relates to methods of treating and/or preventing metabolic and cardiovascular disorders associated with Lyn-kinase activity using the Lyn-modulating compounds.
Reported outcomes include glucose metabolism and weight/fat-pad measures together with Lyn kinase activity.
Claims Coverage
The claims cover one independent method for treating insulin dependent diabetes mellitus in a mammal using a compound of a specified formula or a pharmaceutically acceptable salt. Four dependent inventive features refine administration route, dosage, and co-administration.
Insulin dependent diabetes mellitus treatment with a constrained formula compound
A method of treating insulin dependent diabetes mellitus in a mammal comprising administering a compound of a formula 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 and m is 0 or 1, wherein m+n is less than or equal to 5, or a pharmaceutically acceptable salt thereof.
Intravenous administration of the formula compound
The method further comprises administering the compound intravenously.
Intravenous dosage range per body weight
The method further specifies that the compound is administered intravenously at an amount of 0.1 mg to 35 mg per kilogram of body weight.
Intranasal administration of the formula compound
The method further specifies that the compound is administered intranasally.
Concurrent co-administration with another therapeutic agent
The method includes administering the compound concurrently with another therapeutic agent.
Overall, the claims cover a treatment method for insulin dependent diabetes mellitus using a Lyn-modulating formula compound defined by structural parameter constraints, with further refinements focused on intravenous or intranasal administration, an intravenous dosage range, and concurrent co-administration with another therapeutic agent.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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