Thiazolidinediones of omega-3 polyunsaturated acids as new insulin sensitizers for treating type2 diabetes
Inventors
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-9364465-B2
Publication Date
2016-06-14
Expiration Date
Abstract
The present invention relates to thiazolidinedione derivatives of omega-3 fatty acids as insulin sensitizers, and their use in treating Type2 diabetes, obesity, hypertriglyceridemia, cardiovascular diseases, metabolic diseases, inflammation, renal anemia, and/or Alzheimer's disease: and for modulating activity of peroxisome proliferator-activated receptors (PPARs).
Core Innovation
The invention concerns conjugating a thiazolidinedione (TZD) moiety to omega-3 polyunsaturated fatty acids (PUFAs) to obtain TZD-omega-3 derivatives of Formula (I). The derivatives are defined such that the R group is joined from the methylene moiety formed by reduction of the carboxylic acid of specified cis,cis,cis omega-3 acids, including HTA, ALA, SDA, ETE, ETA, EPA, HPA, DPA, DHA, TPA, and THA.
The compounds are described as “souped-up” TZD-PUFA compounds intended to act as insulin sensitizers. The insulin-sensitizing activity is through enhanced PPARγ activity, and PPARα and PPARδ activity are part of the pharmacological context for these TZD-omega-3 derivatives.
The described scope includes therapeutic and beneficial uses, including Type 2 diabetes and potentially Alzheimer’s disease. The chunk further includes an explicit general reaction scheme and an example preparation for EPA-TZ and DHA-TZ, with in vitro PPARγ transcriptional activation data supporting increased potency for the TZD-PUFA derivatives.
Claims Coverage
The claim set centers on Formula (I) TZD-omega-3 derivatives and related therapeutic and formulation coverage. The inventive features primarily relate to the Formula (I) compounds defined by methylene-joined reduction-derived R groups, with refinements for chemical purity, pharmaceutical formulation composition, dosage forms, and specific therapeutic use constraints.
Formula (I) TZD-omega-3 derivatives via methylene-joined reduction-derived R group
Compounds of Formula (I) wherein R is joined from the methylene moiety formed by reduction of the carboxylic acid of specified cis,cis,cis omega-3 acids, yielding the corresponding thiazolidine-2,4-dione (TZD) derivatives derived from HTA, ALA, SDA, ETE, ETA, EPA, HPA, DPA, DHA, TPA, or THA.
Chemical purity threshold for Formula (I) compound
The compound of claim 1 has chemical purity greater than or equal to 90%.
Pharmaceutical formulation with Formula (I) active and pharmaceutically acceptable components
A pharmaceutical formulation that includes one or more compounds of Formula (I) or pharmaceutically acceptable salts as the active ingredient, plus pharmaceutically acceptable adjuvants and formulation excipients including binders, desiccants, diluents, and excipients.
Pharmaceutical formulation in specified dosage forms
The pharmaceutical formulation is provided in one of the forms: a solution for injection, a gelatin capsule, or a tablet.
Type 2 diabetes treatment formulation with metformin hydrochloride
A pharmaceutical formulation for treating Type 2 diabetes includes metformin hydrochloride as a single formulation.
Alzheimer’s disease effective daily dose regimen constraint
For the Alzheimer’s disease-limited method, the effective amount is administered as a daily dose of about 0.05 to about 5 g/day divided into 1 to 4 doses per day.
The claims focus on Formula (I) TZD-omega-3 derivatives defined by methylene-joined reduction of specified omega-3 carboxylic acids, with dependent claims adding purity, formulation, dosage form, and therapeutic use limitations for Type 2 diabetes and Alzheimer’s disease.
Stated Advantages
Insulin sensitizers activity through enhanced PPARγ activity.
Documented Applications
Treatment or beneficial use in Type 2 diabetes.
Potential application in Alzheimer’s disease.
Interested in licensing this patent?