Bile acid derivatives as FXR/TGR5 agonists and methods of use thereof
Inventors
Wang, Guoqiang • Or, Yat Sun • Shen, Ruichao • Long, Jiang • Dai, Peng • Xing, Xuechao • He, Jing
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-12281140-B2
Publication Date
2025-04-22
Expiration Date
Abstract
The present invention provides compounds of Formula I, pharmaceutical compositions comprising these compounds and methods of using these compounds to prevent or treat FXR-mediated or TGR5-mediated diseases or conditions.
Core Innovation
The invention relates to a series of steroid-like compounds represented by Formula IV-A, Formula IV-B, Formula IV-C, Formula IV-D, Formula V-A, Formula V-B, Formula V-C, Formula VI-A, Formula VI-B, Formula VII-A, Formula VII-B, and Formula IA, with extensive substituent definitions and stereochemical specifications. The compounds include substituted heterocyclic, aromatic, and alicyclic motifs, as well as thioamide, sulfur-containing acyl, sulfonamide, sulfone-linked, and bile acid derivative structures, together with pharmaceutically acceptable salts, solvates, hydrates, esters, and prodrugs in some embodiments.
Representative compounds are listed in tables and structural depictions, including compounds 1 to 75, 76 to 150, 151 to 225, 676 to 686, and Formula III-related examples. The disclosure defines variable groups such as R1, R_a, R_b, R1 to R10, and m, with substituent examples including fluorine, trifluoromethyl, trifluoromethoxy, methyl, ethyl, isopropyl, butyl, t-butyl, propyl, benzyl, vinyl, allyl, aryl, heterocycle, and cyclic amine motifs.
The pharmaceutical compositions described comprise a compound selected from the compounds below or depicted in the images, or a pharmaceutically acceptable salt thereof, together with a pharmaceutically acceptable carrier. The pharmaceutical composition is a solid dosage form suitable for oral administration, and the claimed context ties specific compound selections to that dosage form.
Claims Coverage
The consolidated claim coverage centers on a solid oral pharmaceutical composition comprising a selected compound from the disclosed compound set, or a pharmaceutically acceptable salt thereof, together with a pharmaceutically acceptable carrier. Across the provided items, the inventive features consistently include the selected compound or salt, the carrier, and the solid dosage form suitable for oral administration, with dependent refinements narrowing to capsule or tablet forms and to specific depicted chemical structures.
Solid oral pharmaceutical composition with selected compound or salt and carrier
A pharmaceutical composition comprising a compound selected from the compounds described in the claim text, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, wherein the pharmaceutical composition is a solid dosage form suitable for oral administration.
Capsule or tablet solid dosage form
The pharmaceutical composition is in the form of a capsule or a tablet.
Specific compound structures shown in the images
The included compound is the specific structure shown in the images, or a pharmaceutically acceptable salt thereof.
The claims are directed to a solid oral pharmaceutical composition that includes a selected compound from the disclosed compound sets, or a pharmaceutically acceptable salt, with a pharmaceutically acceptable carrier. Dependent claims repeatedly narrow the composition to capsule or tablet forms and to compounds defined by the referenced chemical structure images.
Stated Advantages
Therapeutic and prophylactic use of invention compounds for treating or preventing FXR-mediated diseases and conditions.
Documented Applications
Treating or preventing FXR-mediated diseases and conditions via therapeutically effective amounts.
Prevention or treatment of FXR-mediated and/or TGR5-mediated diseases/conditions, including metabolic and inflammatory diseases.
Cardiovascular disease, including atherosclerosis.
Metabolic disorders including hypercholesterolemia, hyperlipidemia, insulin resistance, type I and type II diabetes, and obesity.
Chronic liver disease including primary biliary cirrhosis, primary sclerosing cholangitis, NAFLD, and NASH.
Gastrointestinal diseases including inflammatory bowel disease, Crohn's disease, and ulcerative colitis.
Renal disease including diabetic nephropathy.
Autoimmune and inflammatory diseases including rheumatoid arthritis, multiple sclerosis, and psoriasis.
Cancer including colorectal cancer.
Solid oral pharmaceutical composition use in solid dosage form suitable for oral administration.
Interested in licensing this patent?