Small-Molecule CB1 Inhibitors for Obesity, Metabolic Disease, and Liver Disorders
This invention is a family of small-molecule compounds that inhibit cannabinoid receptor type 1 (CB1) activity when administered to a mammal. It offers a single chemical platform for treating obesity, diabetes, dyslipidaemia, atherosclerosis, and liver disorders such as NASH.
Description
CB1 is a receptor on cells that helps regulate appetite, metabolism, and related disease processes. The invention is a defined class of small molecules, described by a core chemical structure (Formula I) with a set of allowed chemical groups at defined positions, that reduce CB1 activity when given to a mammal.The method claims cover administering an effective amount of one of these compounds, or a pharmaceutically acceptable salt (a common drug-grade form of the compound), to inhibit CB1 activity. The claims also cover using this inhibition to treat obesity, fear, metabolic-related disorders, diabetes, dyslipidaemia, atherosclerosis, and liver disorders. The liver disorders named are fatty liver disease, nonalcoholic steatohepatitis (NASH), cirrhosis, and liver cancer.
Applications
- Anti-obesity and weight-management therapeutics- Treatment of diabetes and other metabolic-related disorders
- Therapies for dyslipidaemia and atherosclerosis
- Treatment of liver disorders, including fatty liver disease, NASH, cirrhosis, and liver cancer
- Treatment of fear-related conditions
Advantages
- Defined small-molecule chemical class with a specific structural formula and named lead compounds- Flexible scaffold, with a broad range of permitted substituents supporting further optimization
- One mechanism (CB1 inhibition) applicable to several related conditions: obesity, diabetes, dyslipidaemia, atherosclerosis, and liver disease
- Claimed use across the spectrum of liver disease, from fatty liver to NASH, cirrhosis, and liver cancer
- Deliverable as the free compound or a pharmaceutically acceptable salt