Functionalized long-chain hydrocarbon mono- and di-carboxylic acids and their use for the prevention or treatment of disease

Inventors

Oniciu, Daniela Carmen

Assignees

Espervita Therapeutics Inc

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 disclosed subject matter relates to pharmaceutical compositions comprising an effective amount of a compound having a specific chemical structure, or a pharmaceutically acceptable salt or solvate thereof, together with sorafenib or lenvatinib and a pharmaceutically acceptable carrier or vehicle. The compounds are described by multiple related structural formulae and chemical structure depictions, including aromatic, substituted phenyl, biaryl, bis-aryl/alkyl carboxylic acid, and carboxylic-acid-containing scaffold variants with phenolic hydroxyl and carboxylic acid functionality.

The disclosure further provides multiple structural depictions and formula-defined families, including Formula (IC), Formula (IIIA), Formula (IIIB), Formula (III), and related compound sets such as I-61 through I-77, I-71 and I-72, CHEM-US-00819 through CHEM-US-00899, C00390 through C00414, and Table A-1, Table A-3, and Table B2 embodiments. The disclosed variants include carboxylic acid and carboxylate forms, phenolic hydroxyl substituents, halogens, ether or ester forms, sulfoxide or sulfone analogs, and pharmaceutically acceptable salts and solvates.

The disclosure also mentions functionalized long-chain hydrocarbon mono- and di-carboxylic acids, aryl-alkyl-cyclopropane bis/mono-carboxylic acids, and bistructured phenyl-linked bis-cyclopropane carboxylic acid structures. In addition, the provided content states disease-related targets and biological rationale in connection with abnormal liver condition, liver disease, fibrosis, cirrhosis, NF-κB, stellate cell activation, PPAR activation, ATP citrate lyase, and acetyl-CoA carboxylase, as well as figure captions indicating in vitro anti-lipogenesis/anti-proliferation effects and combination activity with sorafenib and lenvatinib.

Claims Coverage

The consolidated claim coverage centers on one independent pharmaceutical composition claim. The claim includes three main inventive elements: an effective amount of a compound having a specified structure (or a pharmaceutically acceptable salt or solvate), sorafenib or lenvatinib, and a pharmaceutically acceptable carrier or vehicle.

The independent claim coverage is a pharmaceutical composition combining an effective amount of a structure-defined compound, including pharmaceutically acceptable salt or solvate forms, with sorafenib or lenvatinib and a pharmaceutically acceptable carrier or vehicle.

Stated Advantages

Documented Applications