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-11267778-B2
Publication Date
2022-03-08
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 a method for treating or preventing hepatocellular carcinoma by administering to a subject in need thereof an effective amount of a compound having a specified chemical structure, or a pharmaceutically acceptable salt or solvate thereof. The disclosed compounds are defined by multiple related structural embodiments, including substituted aromatic, cyclopropane-1-carboxylic acid, carboxylic acid, ester, hydroxyl, hydrophobic scaffold, long-chain hydrocarbon, biphenyl/aryl, polyene/lipid-like, cyclopropyl, and substituted carboxylic acid scaffold variants presented in formulas, tables, and structure depictions.
The compound descriptions include Formula (IE), Formula (IF), Formula (II), Formula (IC), Formula (IA)/(IB)/(IC), and related exemplified structures, with variable substituents and functional-group definitions. The disclosure also recites generic formulas with substituent variables, specific compound examples, and compositions containing the compounds, including pharmaceutically acceptable carrier or vehicle forms and optional additional pharmaceutically active agents.
The material links these compound structures to hepatocellular carcinoma treatment or prevention and related pathological states. It also associates the compounds with target and biomarker modulation involving NF-baB, PPAR, ATP citrate lyase, and acetyl-CoA carboxylase 1/2, and reports biological contexts including anti-liver-cancer activity, clonogenicity, hepatocyte lipogenesis, and tumor cell proliferation.
Claims Coverage
The consolidated material identifies one independent claim directed to treating or preventing hepatocellular carcinoma by administering an effective amount of a compound having a specified chemical structure, with pharmaceutically acceptable salt or solvate coverage. The claim sets also include a dependent feature that adds further administration of sorafenib or lenvatinib, giving 2 inventive features in total.
Administration of a specified compound for hepatocellular carcinoma treatment or prevention
A method for treating or preventing hepatocellular carcinoma by administering to a subject in need thereof an effective amount of a compound having the specified structure, or a pharmaceutically acceptable salt or solvate thereof.
Further administration of sorafenib or lenvatinib
The method further includes administering sorafenib or lenvatinib to the subject.
Overall, the claim coverage is directed to hepatocellular carcinoma treatment or prevention through administration of an effective amount of a structurally defined compound, with some claims further specifying sorafenib or lenvatinib as an additional therapeutic component.
Stated Advantages
Reduces serum CRP, SAA, ALT, AST, ALP, and GGT.
Reduces triglycerides in liver.
Elevates HDL.
Provides target modulation including NF-baB inhibition and PPAR activation.
Modulates ATP citrate lyase and acetyl-CoA carboxylase 1/2.
Exhibits anti-proliferative activity against hepatocellular carcinoma cell models.
Clonogenicity inhibition reported for selected compounds.
Synergistic antiproliferative effects reported in combination with sorafenib or lenvatinib.
Treating or preventing hepatocellular carcinoma.
Documented Applications
Treating or preventing hepatocellular carcinoma in a subject in need thereof by administering an effective amount of a compound having the specified structure, or a pharmaceutically acceptable salt or solvate thereof.
Co-administration treatment/prevention contexts that include further administering sorafenib or lenvatinib to the subject.
Compositions containing the compounds, including pharmaceutically acceptable carrier or vehicle forms and optional additional pharmaceutically active agents.
Anti-liver-cancer activity testing of selected compounds in Hep3B and Hepa1-6, including proliferation reduction/IC50 and clonogenicity assays.
Combination studies demonstrating synergistic antiproliferative effects with sorafenib or lenvatinib.
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