Functionalized long-chain hydrocarbon mono- and di-carboxylic acids and their use for the prevention or treatment of disease
Inventors
Assignees
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Publication Number
US-12180151-B2
Publication Date
2024-12-31
Expiration Date
Abstract
This invention provides compounds of Formulae (IA), (IB), (IC), (ID), (IE), (IF), (IG), (IH), (IJ), (IK), (IL), (II), (III), (IIIA), and (IIIB); pharmaceutically acceptable salts and solvates thereof; and compositions thereof. This invention further provides methods for treating a disease, including but not limited to, liver disease or an abnormal liver condition; cancer (such as hepatocellular carcinoma or cholangiocarcinoma); a malignant or benign tumor of the lung, liver, gall bladder, bile duct or digestive tract; an intra- or extra-hepatic bile duct disease; a disorder of lipoprotein; a lipid-and-metabolic disorder; cirrhosis; fibrosis; a disorder of glucose metabolism; a cardiovascular or related vascular disorder; a disease resulting from steatosis, fibrosis, or cirrhosis; a disease associated with increased inflammation (such as hepatic inflammation or pulmonary inflammation); hepatocyte ballooning; a peroxisome proliferator activated receptor-associated disorder; an ATP citrate lyase disorder; an acetyl-coenzyme A carboxylase disorder; obesity; pancreatitis; or renal disease.
Core Innovation
The invention relates to structure-defined compound families, including functionalized long-chain hydrocarbon mono- and di-carboxylic acids, carboxylic-acid compounds, and related claimed structures. The disclosed compounds include Formula (IA), Formula (IB), Formula (IC), Formula (ID), Formula (II), Formula (III), Formula (IIIA/IIIB), Formula (IE), Formula (IF)/(IH)/(IJ)/(IK)/(IL), and related subformulas, with pharmaceutically acceptable salts, solvates, or hydrates thereof.
The compound families vary by substituents, linkers, and structural motifs including aryl, cyclopropane, biphenyl, polycyclic, substituted aromatic, diaryl, and heteroatom-containing motifs such as O, S, Se, sulfoxide, sulfone, and amine options. The examples and structure depictions identify multiple members with carboxylic acid, ester, hydroxyl, alkyl, phenyl, and phenolic hydroxyl substitution patterns.
The patent text frames these compounds as therapeutic agents for liver-related indications, repeatedly linking them to treatment or prevention of non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), and inhibition, reduction, or delay of progression of liver fibrosis. The documents also identify disease-use overviews for cirrhosis, hepatocyte ballooning, inflammatory disorders, cancers including HCC and cholangiocarcinoma, and cardiometabolic and vascular disorders.
Claims Coverage
The consolidated claim coverage centers on structure-defined compound families and extends to pharmaceutically acceptable salts or solvates. Across the combined items, the inventive features are the specified compound structures, pharmaceutical compositions with a pharmaceutically acceptable carrier or vehicle, and therapeutic methods for NAFLD, NASH, and liver fibrosis progression.
Structure-defined compound families with salts or solvates
Compounds having the specified structures, including pharmaceutically acceptable salts or solvates thereof, across Formula (IA), Formula (IB), Formula (IC), Formula (ID), Formula (II), Formula (III)/(IIIA/IIIB), Formula (IE), Formula (IF)/(IH)/(IJ)/(IK)/(IL), and related claimed structure sets.
Pharmaceutical composition with carrier or vehicle
A pharmaceutical composition comprising the claimed compound or a pharmaceutically acceptable salt or solvate thereof together with a pharmaceutically acceptable carrier or vehicle.
Treatment or prevention of NAFLD
A method for treating or preventing non-alcoholic fatty liver disease (NAFLD) by administering an effective amount of the claimed compound or a pharmaceutically acceptable salt or solvate thereof to a subject in need.
Treatment or prevention of NASH
A method for treating or preventing non-alcoholic steatohepatitis (NASH) by administering an effective amount of the claimed compound or a pharmaceutically acceptable salt or solvate thereof to a subject in need.
Inhibiting, reducing, or delaying liver fibrosis progression
A method for inhibiting, reducing, or delaying progression of a subject’s liver fibrosis by administering an effective amount of the claimed compound or a pharmaceutically acceptable salt or solvate thereof.
The claims collectively center on structure-defined compound families, extend to pharmaceutically acceptable salts or solvates and pharmaceutical compositions, and include therapeutic method coverage for NAFLD, NASH, and liver fibrosis progression.
Stated Advantages
Lowering inflammatory markers including CRP and SAA.
Lowering liver enzymes including ALT, AST, ALP, and GGT.
Reducing liver triglycerides.
Elevating HDL.
Inhibiting NF-κB.
Inhibiting stellate cell activation.
Activating PPAR.
Modulating ATP citrate lyase and acetyl-CoA carboxylase 1/2.
Inhibiting mouse primary hepatocyte lipogenesis.
Producing anti-proliferative and anti-clonogenic effects in hepatoma cell lines.
Providing combination and/or synergy with sorafenib and lenvatinib in hepatoma cell line effects.
Treating or preventing non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH).
Inhibiting, reducing, or delaying progression of liver fibrosis.
Documented Applications
Therapeutic methods for treating or preventing non-alcoholic fatty liver disease (NAFLD).
Therapeutic methods for treating or preventing non-alcoholic steatohepatitis (NASH).
Therapeutic methods that inhibit, reduce, or delay progression of liver fibrosis.
Disease-use overview including liver disease and abnormal liver conditions, cirrhosis and fibrosis, NAFLD/NASH-related conditions, hepatocyte ballooning, inflammatory disorders, cancers including HCC and cholangiocarcinoma.
Disease-use overview for cardiometabolic and vascular disorders, including lipoprotein disorder and hyperlipidemia-related conditions.
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