Functionalized long-chain hydrocarbon mono- and di-carboxylic acids and derivatives thereof, and their use for the prevention or treatment of disease
Inventors
Oniciu, Daniela Carmen • STEINBERG, Gregory R. • HEATON, Spencer • Newton, Roger Schofield • LALLY, James Stuart Vincent • GAUTAM, Jaya
Assignees
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Publication Number
US-11737995-B2
Publication Date
2023-08-29
Expiration Date
Abstract
Methods for treating or preventing kidney diseases and fibrosis, such as chronic kidney disease (CKD), kidney fibrosis, heart fibrosis, uterine fibrosis, and cystic fibrosis, with 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.
Core Innovation
The invention defines a class of structure-defined compounds with variable substituents C1 and C2, where C1 and C2 are selected from COOH or CO-CoA in different combinations, together with variable substituents R1 and R2, with options including H, halogens, CF3, and (C1-C4)alkyl. The disclosure presents multiple embedded chemical structures and chemical file identifiers that illustrate alternative members of the same compound family, including aromatic, cyclopropane-containing, and CoA-containing variants.
The disclosed subject matter further encompasses Coenzyme A (CoA) ester compounds, CoA conjugates, and pharmaceutically acceptable salts and solvates of the compounds. The patent presents several compound classes and representative structural embodiments, including Formula (I), Formula (IB), Formula (IH), and Formula (IJ), as well as related dibenzo/biaryl-dicarboxylic acid derivative compounds and substituted aromatic scaffold variants.
The invention is directed to using these structure-defined compounds in methods for treating autosomal polycystic kidney disease and kidney fibrosis by administering an effective amount of a compound having the specified structure, or a pharmaceutically acceptable salt or solvate thereof. The disclosed methods also include dependent refinements for specific autosomal polycystic kidney disease variants and embodiments in which a second pharmaceutically active agent is administered alongside the structure-defined compound, including pioglitazone or tolvaptan.
Claims Coverage
The consolidated claim coverage includes two independent method claims, one for autosomal polycystic kidney disease and one for kidney fibrosis. Across the independent claims, the inventive features center on administering an effective amount of a compound having a specified chemical structure, including pharmaceutically acceptable salts or solvates, with dependent refinements for disease variants and optional combination administration with another pharmaceutically active agent. The number of core inventive features is two.
Treating autosomal polycystic kidney disease with a structure-defined compound
A method for treating autosomal polycystic kidney disease comprising administering to a subject in need thereof an effective amount of a compound having the structure, or a pharmaceutically acceptable salt or solvate thereof.
Treating kidney fibrosis with a structure-defined compound
A method for treating kidney fibrosis comprising administering to a subject in need thereof an effective amount of a compound having the structure, or a pharmaceutically acceptable salt or solvate thereof.
Treating autosomal polycystic kidney disease variants
The method includes autosomal dominant polycystic kidney disease, autosomal recessive polycystic kidney disease, or autosomal dominant polycystic kidney disease type 1 with tuberous sclerosis.
Combination treatment with another pharmaceutically active agent
The subject is treated with another pharmaceutically active agent in addition to the structure-defined compound.
Using pioglitazone as the other pharmaceutically active agent
The other pharmaceutically active agent is pioglitazone or a pharmaceutically acceptable salt thereof.
Using tolvaptan as the other pharmaceutically active agent
The other pharmaceutically active agent is tolvaptan.
The claims cover administration of an effective amount of a structure-defined compound, including pharmaceutically acceptable salts or solvates, for treating autosomal polycystic kidney disease or kidney fibrosis. Dependent claims further narrow autosomal polycystic kidney disease to specific variants and include combination treatment with pioglitazone or tolvaptan.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Treating autosomal polycystic kidney disease by administering an effective amount of a compound having the specified structure, or a pharmaceutically acceptable salt or solvate thereof.
Treating kidney fibrosis by administering an effective amount of a compound having the specified structure, or a pharmaceutically acceptable salt or solvate thereof.
Combination use with an additional pharmaceutically active agent, including pioglitazone (or a pharmaceutically acceptable salt) and tolvaptan.
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