Treatment for obesity
Inventors
Li, Chiang J. • Derdak, Zoltan • STEVANOVIC, Darko • Liu, Jifeng
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-12390460-B2
Publication Date
2025-08-19
Expiration Date
Abstract
The invention provides novel methods of treating or preventing obesity or overweight and closely associated comorbidities therewith in a mammalian subject including human.
Core Innovation
The invention relates to treating or preventing obesity, overweight, type II diabetes and the metabolic syndrome in a mammal by administering a pharmaceutical composition comprising a compound of Formula I, including an enantiomer, diastereomer, tautomer, or pharmaceutically acceptable salt or solvate thereof. The composition comprises a pharmaceutically acceptable excipient, carrier, or diluent, and the method is framed around therapeutic objectives including reducing BMI and/or body weight, improving insulin sensitivity and liver function, and improving metabolic syndrome diagnostic criteria.
The structural scope includes extensive substituent definitions for Formula I, with variable elements defined by symbols R1, R2, R3, R4, R5, R6, R7, Ra, Rb, Rc, Rd, Re and related substituent classes. Formula VII embodiments and related sub-forms further specify allowable compositions for X, Z, and A, together with options for R1, R3, R4, R5/R6/R7, and additional variants, including illustrated structures identified as VII-a through VII-m.
The description supports the therapeutic approach with in vivo animal data and cell-culture assay figure descriptions, including body weight and caloric intake measures, triglycerides and adipose tissue marker outputs, and liver-related outcomes such as NAFLD improvement and intracellular triglyceride accumulation in human liver cells. Additional biomarker and gene expression context is stated through FGF21, leptin, TGFβ, RORA, ACADM, ACOX1, and MLYCD.
Claims Coverage
The document includes independent claims directed to a method for treating or preventing obesity, overweight, type II diabetes, and/or metabolic syndrome in a mammal by administering a pharmaceutical composition containing a compound of Formula I. The inventive subject matter combines therapeutic use of Formula I compounds with extensive structural definitions for allowable substituent symbols.
Treating or preventing obesity, overweight, type II diabetes, and metabolic syndrome
A method for treating a condition selected from obesity, overweight, type II diabetes and the metabolic syndrome in a mammal by administering to a mammalian subject in need thereof a therapeutically effective amount of a pharmaceutical composition.
Pharmaceutical composition with a compound of Formula I for the treatment or prevention
Administering a pharmaceutical composition comprising a compound of Formula I, including an enantiomer, diastereomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, effective in the treatment or prevention of a condition selected from obesity, overweight, type II diabetes and the metabolic syndrome.
Composition includes a pharmaceutically acceptable excipient, carrier, or diluent
The pharmaceutical composition further comprises a pharmaceutically acceptable excipient, carrier, or diluent.
Compound structure scope for Formula I substituent symbols
Using a compound of Formula I in which the symbols are independently selected from the defined substituent classes for R1, R2, R3, R4, R5, R6, R7, Ra, Rb, Rc, Rd, Re, with Rb and Rc together optionally forming a heterocycle with the N to which they are bonded, thereby defining the allowed structural substituent pattern for the administered compound.
Overall, the claim coverage is concentrated on administering a therapeutically effective amount of a Formula I compound, including enantiomer, diastereomer, tautomer, or pharmaceutically acceptable salt or solvate, within a pharmaceutical composition containing a pharmaceutically acceptable excipient, carrier, or diluent to treat or prevent obesity, overweight, type II diabetes, and/or metabolic syndrome in a mammal.
Stated Advantages
Reduces body weight in HFD-fed obese mice while not reducing food/water intake.
Improves fat absorption/apetite-energy marker readouts and alters adipose morphology and TGF-β expression.
Modulates metabolic gene expression including fat oxidation and suppression of de novo lipogenesis, and affects insulin resistance-related markers.
Increases FGF21 and decreases leptin.
Improves liver phenotype.
Enhances glucose tolerance and insulin sensitivity (OGTT/ITT).
Inhibits triglyceride/fat accumulation in human HepG2 cells under palmitoleate challenge.
Reducing BMI and/or body weight.
Improving insulin sensitivity and liver function.
Improving metabolic syndrome diagnostic criteria.
Treating or preventing a condition selected from obesity, overweight, type II diabetes and the metabolic syndrome in a mammal.
The method is effective for treatment or prevention using a therapeutically effective amount of a pharmaceutical composition comprising a compound of Formula I.
Documented Applications
Treatment or prevention of obesity, overweight, type II diabetes, and the metabolic syndrome in a mammal, including biomedical assay use of Compound 14-3 in HFD-fed obese mice.
Assessment in assays showing changes in adipose morphology, TGF-β expression, metabolic gene expression, FGF21/leptin, liver phenotype, glucose tolerance, insulin sensitivity, and triglyceride/fat accumulation in HepG2 cells under palmitoleate challenge.
Treatment and/or prevention of obesity, overweight, type II diabetes, and the metabolic syndrome in mammals, including humans, using pharmaceutical compositions containing compounds of Formula I.
Reduction or amelioration of at least one obesity/overweight/type II diabetes/metabolic syndrome-associated symptom or indication selected from the listed clinical measures.
Interested in licensing this patent?