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 structure-defined compounds having substituted aromatic or biphenyl-like cores with phenolic hydroxyl groups, long aliphatic or alkyl linker chains, and terminal carboxylic acid groups. The disclosed structures include related variants with cyclopropyl motifs, carboxylate or ester-like features, and different substitution patterns while maintaining the same overall scaffold framework.

The compounds are defined by chemical structure and include pharmaceutically acceptable salt or solvate forms. The disclosure also includes pharmaceutical compositions comprising the structure-defined compound and a pharmaceutically acceptable carrier or vehicle, with some embodiments also referring to additional active agents.

The methods disclosed use an effective amount of the structure-defined compound, or a pharmaceutically acceptable salt or solvate thereof, for liver-related indications. The stated therapeutic uses include treating cirrhosis, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), and inhibiting, reducing, or delaying advancement of a subject's liver fibrosis.

Claims Coverage

The consolidated independent claims cover a structure-defined compound, a pharmaceutical composition comprising that compound and a pharmaceutically acceptable carrier or vehicle, and therapeutic methods using the same compound for liver indications. Across the claims, the key inventive features are the specific chemical structure definition, inclusion of pharmaceutically acceptable salt or solvate forms, and treatment of cirrhosis, NAFLD, NASH, and liver fibrosis advancement. Four inventive features are consistently present.

Overall, the claim coverage is centered on structure-defined compounds with pharmaceutically acceptable salt or solvate forms, their formulation in pharmaceutical compositions with a pharmaceutically acceptable carrier or vehicle, and their use in methods for treating cirrhosis, NAFLD, NASH, and inhibiting, reducing, or delaying liver fibrosis advancement.

Stated Advantages

Documented Applications