Antifibrotic compounds and uses thereof
Inventors
Panicker, Bijoy • Mishra, Rama K. • Lim, Dong Sung • Oehlen, Lambertus J. W. M. • Jung, Dawoon
Assignees
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Publication Number
US-11504359-B2
Publication Date
2022-11-22
Expiration Date
Abstract
The present invention provides compounds having the general structural formula (I) and pharmaceutically acceptable derivatives thereof, as described generally and in classes and subclasses herein, and additionally provides pharmaceutical compositions thereof, and methods for the use thereof for the treatment of any of a number of conditions or diseases involving abnormal or excessive fibrosis.
Core Innovation
The patent describes antifibrotic small-molecule scaffolds defined by Formulas (I)–(IV) with variable substituents (R1–R6, A, B), including pharmaceutically acceptable salts and prodrugs. The compounds are presented together with specific substituted examples within the described scaffold families and are suitable for pharmaceutical use, including compound forms intended for administration as medicines.
The patent addresses abnormal or excessive fibrosis by providing therapeutic compounds and pharmaceutical compositions for preventing and treating diseases involving abnormal or excessive fibrosis. The described disease contexts include liver fibrosis and cirrhosis, ischemia-reperfusion injury, stroke and cerebral infarction, cardiac fibrosis and atherosclerosis, renal fibrosis, idiopathic pulmonary fibrosis, and scleroderma and skin fibrosis.
The document further reports biological findings associated with the described compounds, including kinase inhibition activities (KDR and PDGFR) and cellular inhibition of receptor phosphorylation and collagen production. It also describes in vivo antifibrotic efficacy in hepatic, renal, lung, and skin fibrosis models, with reductions reported for hydroxyproline, fibrotic scores, and fibrotic marker proteins.
Claims Coverage
The provided independent claim set includes one independent claim covering a pharmaceutical composition containing selected (Z)-substituted pyrrolo[2,3-b]pyridine/methylene ester compounds, or pharmaceutically acceptable salts, with at least one pharmaceutically acceptable carrier, specifically formulated as a capsule or tablet.
Selected (Z)-methyl pyrrolo[2,3-b]pyridine/methylene ester compounds in a pharmaceutical composition
A pharmaceutical composition comprising a compound selected from the enumerated (Z)-methyl pyrrolo[2,3-b]pyridine/methylene ester variants listed in the claim, or a pharmaceutically acceptable salt thereof.
Pharmaceutically acceptable carrier
The pharmaceutical composition further comprises at least one pharmaceutically acceptable carrier.
Capsule or tablet dosage form
The pharmaceutical composition is in the form of a capsule or tablet.
The inventive coverage is grounded in composition of the specified enumerated (Z)-methyl pyrrolo[2,3-b]pyridine/methylene ester compounds or salts, inclusion of at least one pharmaceutically acceptable carrier, and specification of the capsule or tablet form.
Stated Advantages
Antifibrotic activity in preventing or treating diseases involving abnormal or excessive fibrosis.
Reduction of fibrosis readouts in reported in vivo fibrosis models, including reductions in hydroxyproline, fibrotic scores, and fibrotic marker proteins.
Kinase inhibition activities (KDR and PDGFR) and cellular inhibition of receptor phosphorylation and collagen production are reported for the described compounds.
Documented Applications
Preventing and treating diseases involving abnormal or excessive fibrosis, including liver fibrosis and cirrhosis.
Preventing and treating ischemia-reperfusion injury.
Preventing and treating stroke and cerebral infarction.
Preventing and treating cardiac fibrosis and atherosclerosis.
Preventing and treating renal fibrosis.
Preventing and treating idiopathic pulmonary fibrosis.
Preventing and treating scleroderma and skin fibrosis.
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