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 invention relates to a pharmaceutical composition comprising an effective amount of a compound having a specified chemical structure, or a pharmaceutically acceptable salt or solvate thereof, together with sorafenib or lenvatinib, and a pharmaceutically acceptable carrier or vehicle. The disclosed structures are presented as related chemical structure depictions, including substituted aromatic carboxylic acid derivatives, biphenyl/tetralin-like scaffold molecules, cyclopropane-containing aromatic dicarboxylic acid scaffold molecules, and related small molecules with carboxylic acid or acid-derived groups and phenolic hydroxyl groups.

The compound component is described through multiple structure variants that maintain aromatic or polyalkyl backbone features, terminal carboxylic acid groups, and substituent variation including hydroxyl, ester-like, and methyl or branched alkyl motifs. Some depictions also include cyclopropyl substituents, ether linkage involving a cyclopropyl group, or lipophilic chain elements, while other disclosures refer to Formula (II), Formula (III), and/or Formula (IIIB) compounds with variable substituent and linkage parameters.

In a separate disclosed context, multiple substituted aromatic and aliphatic diacid or ester intermediates and final carboxylic acid compounds are described, and biological assay results are reported in liver cancer cell lines. The combination studies describe synergistic inhibition with sorafenib or lenvatinib, and the assays include anti-proliferative effects and clonogenicity assessments in Hep3B and Hepa1-6.

Claims Coverage

The consolidated input provides multiple independent composition claims, each with three common required components: an effective amount of a structurally defined compound, or a pharmaceutically acceptable salt or solvate, sorafenib or lenvatinib, and a pharmaceutically acceptable carrier or vehicle. The structural definitions vary across the inputs, but the claim format is consistent.

Overall, the claim coverage is directed to pharmaceutical compositions that combine a structure-defined compound class with sorafenib or lenvatinib and a pharmaceutically acceptable carrier or vehicle.

Stated Advantages

Documented Applications