Functionalized long-chain hydrocarbon mono- and di-carboxylic acids and derivatives thereof, and their use for the prevention or treatment of disease
Inventors
Assignees
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Publication Number
US-11730712-B2
Publication Date
2023-08-22
Expiration Date
Abstract
This invention provides compounds of Formulae (I), (IA), (IB), (IC), (ID), (IE), (IF), (IG), (IH), (IJ), (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 compound having a specified structure that includes the motifs CO—CoA and CoA-OC—, together with pharmaceutically acceptable salt or solvate forms. The compound family is defined by variable substituent patterns, including C1 and C2 positions selected from COOH and CO—CoA in different combinations, including swapped combinations. The structures are presented as substituted aromatic, polyene-like, steroid-like, cyclopropyl-containing, hydrophobic, and related scaffold variants.
The disclosure further includes R1 and R2 substituent variability, with H, (C1-C4)alkyl, halogens F, Cl, Br, and CF3, and in some embodiments alkoxy, ether, ester-like, hydroxyl, and phenoxy-type forms. The described compound class also includes CoA mono- and di-thioester or CoA ester forms, with examples shown as substituted arene derivatives, carboxylic acid derivatives, and cyclopropane-carboxylic acid derivatives. Representative structures in tables and drawings illustrate the same broad structural theme across the disclosed formula families.
The specification also presents isolated and purified forms and pharmaceutical composition embodiments in which the compound, or its pharmaceutically acceptable salt or solvate, is combined with a pharmaceutically acceptable carrier or vehicle. The compound scope is repeatedly illustrated by formula-defined embodiments and by compounds having aromatic, aliphatic, and cyclopropyl-substituted frameworks with carboxylic acid, CoA-linked, and salt or solvate variants.
Claims Coverage
The consolidated claim coverage centers on one independent claim directed to a compound having the CO—CoA and CoA-OC— structural motifs, with pharmaceutically acceptable salt or solvate coverage. Across the inputs, the recurring inventive features are the defined compound structure, isolated and purified forms, and pharmaceutical compositions containing the compound with a pharmaceutically acceptable carrier or vehicle and a specified compound weight-percent range.
Defined compound structure with CO—CoA and CoA-OC— motifs
A compound having a specified structure in which CO—CoA and CoA-OC— have the defined structure, including positional variants where C1 and C2 are COOH and/or CO—CoA in different combinations.
Pharmaceutically acceptable salt or solvate forms
The compound is covered together with pharmaceutically acceptable salts or solvates of the defined structure.
Isolated and purified compound forms
The compound, or a pharmaceutically acceptable salt or solvate thereof, is covered in isolated and purified form.
Pharmaceutical composition with carrier or vehicle and defined wt% range
A pharmaceutical composition including the compound, or a pharmaceutically acceptable salt or solvate thereof, together with a pharmaceutically acceptable carrier or vehicle, with the compound present at 10±1 wt% to 99±1 wt% of the total composition weight.
Overall, the claims are directed to compounds defined by the CO—CoA and CoA-OC— motifs, extended to pharmaceutically acceptable salts or solvates, and further narrowed to isolated and purified forms and pharmaceutical compositions containing a carrier or vehicle and a specified compound weight-percent range.
Stated Advantages
Provides a compound suitable for pharmaceutical use, including pharmaceutically acceptable salts or solvates.
Provides isolated and purified compound forms.
Provides pharmaceutical compositions including a pharmaceutically acceptable carrier or vehicle with a specified compound content range of 10±1 wt% to 99±1 wt%.
Documented Applications
Pharmaceutical composition use cases, where the compound or a pharmaceutically acceptable salt or solvate is included with a pharmaceutically acceptable carrier or vehicle.
Treatment and/or prevention of liver disease or an abnormal liver condition, including fibrosis/steatosis/NASH.
Treatment and/or prevention of cancers including hepatocellular carcinoma (HCC) and cholangiocarcinoma.
Treatment and/or prevention of inflammatory and metabolic disorders.
Inhibition of viral infection, including viral replication inhibition.
Therapeutic and prophylactic uses including inhibiting production of beta-hCG, beta-2-microglobulin, B-cell immunoglobulin, and alpha-fetoprotein.
Modulating hepatic lipid/sterol synthesis via an ACC/malonyl-CoA/CPT-I regulatory axis and ATP citrate lyase (ACLY) and ACC1/ACC2 modulation or inhibition.
Lowering HDL/LDL for treating metabolic syndrome and dyslipidemia.
Reducing fat/cholesterol content in livestock meat/poultry eggs.
Reducing cancer risk or cancer growth, including hepatocellular carcinoma and other tumor types.
Treating or preventing viral infections, including oncoviruses such as HPV, HBV, HCV, and EBV.
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