Fused thiophene derivatives and their uses
Inventors
MELDRUM, Eric • DE CHASSEY, BENOÎT • MACHIN, PETER • LANARO, Roberta • Macleod, Calum • Malagu, Karine Fabienne • Proisy, Nicolas • VESEY, DAVID ROBERT • WINSHIP, PAUL COLIN MICHAEL • Chambers, Mark • Paparin, Jean-Laurent
Assignees
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Publication Number
US-11603368-B2
Publication Date
2023-03-14
Expiration Date
Abstract
The present invention relates to a new class of fused thiophene derivatives and their uses for treating diseases such as infection, cancer, metabolic diseases, cardiovascular diseases, iron storage disorders and inflammatory disorders.
Core Innovation
The invention relates to substituted thieno[2,3-c]pyridine-3-carboxylic acid compounds, including benzamido and benzoylamino derivatives, with a thieno[2,3-c]pyridine core and defined 6-aryl substituents. The compounds include fluoro, difluoro, methoxy, trifluoromethyl, o-tolyl, alkyl, and related aryl substitution patterns, and some are presented as salt or protected forms, including a formate salt and a Boc-protected acid.
The compounds are represented by Formula (I) with variable definitions for X, n, R1a/R1b/R1c/R1d/R2/R3, and the embodiments include pharmaceutically acceptable salts and stereoisomers, including enantiomers and diastereoisomers. The examples and claim material identify specific compounds such as 2-benzamido and 2-[(benzoyl)amino] derivatives, including a formate salt example.
The patent also states that these compounds are associated with NEET proteins, including mitoNEET (CISD1), NAF-1 (CISD2), and Miner2/MiNT (CISD3), and describes them as modulators of Fe-S cluster binding. The medicinal use is broadly described for antiviral, antitumor, metabolic, cardiovascular, inflammatory, iron storage, aging, and neurodegenerative disease contexts.
Claims Coverage
The independent claim coverage identifies a defined group of specific substituted thieno[2,3-c]pyridine-3-carboxylic acid compounds, with one dependent claim adding a pharmaceutical composition comprising an acceptable pharmaceutical excipient. The inventive features center on the fixed fused-ring scaffold, the 2-position amide or benzamido linkage, the 6-position aryl substitution pattern, and one formate salt embodiment.
Selected substituted thieno[2,3-c]pyridine carboxylic acid compounds
A compound selected from the group consisting of 2-benzamido-6-phenyl-5,7-dihydro-4H-thieno[2,3-c]pyridine-3-carboxylic acid; 2-benzamido-6-(4-fluoro-2-methylphenyl)-5,7-dihydro-4H-thieno[2,3-c]pyridine-3-carboxylic acid; 2-[(3,4-dimethoxybenzoyl)amino]-6-(4-fluoro-2-methylphenyl)-5,7-dihydro-4H-thieno[2,3-c]pyridine-3-carboxylic acid; 2-[(2-fluoro-4-methoxybenzoyl)amino]-6-(4-fluoro-2-methylphenyl)-5,7-dihydro-4H-thieno[2,3-c]pyridine-3-carboxylic acid; 2-benzamido-6-(2,4-difluorophenyl)-5,7-dihydro-4H-thieno[2,3-c]pyridine-3-carboxylic acid; 2-benzamido-6-(o-tolyl)-5,7-dihydro-4H-thieno[2,3-c]pyridine-3-carboxylic acid; 2-benzamido-6-[4-(trifluoromethyl)phenyl]-5,7-dihydro-4H-thieno[2,3-c]pyridine-3-carboxylic acid; 2-[(3,4-dimethoxybenzoyl)amino]-6-(4-fluorophenyl)-5,7-dihydro-4H-thieno[2,3-c]pyridine-3-carboxylic acid; 6-tert-butoxycarbonyl-2-[(2-methylbenzoyl)amino]-5,7-dihydro-4H-thieno[2,3-c]pyridine-3-carboxylic acid; and 6-iso-butyl-2-[(2-methylbenzoyl)amino]-5,7-dihydro-4H-thieno[2,3-c]pyridine-3-carboxylic acid formate salt.
Pharmaceutical composition with acceptable excipient
A pharmaceutical composition comprising a compound as defined in claim 1, and an acceptable pharmaceutical excipient.
Overall, the claims cover a specifically enumerated set of substituted thieno[2,3-c]pyridine-3-carboxylic acid compounds, including benzamido and substituted benzamido variants and a formate salt, and further cover pharmaceutical compositions containing one of the defined compounds together with an acceptable pharmaceutical excipient.
Stated Advantages
Demonstrates antiviral effects.
Can be used for therapeutic indications including infections (viral and bacterial), cancer, metabolic disease, cardiovascular disease, inflammatory disorders, and iron-storage disorders.
Acts as modulators affecting Fe-S cluster binding by NEET proteins, characterized as stabilisers or destabiliser of Fe-S cluster binding.
Documented Applications
Treatment of viral infections and bacterial infections, including influenza virus.
Treatment of cancers as antitumor agents.
Treatment of metabolic disorders and metabolic disease.
Treatment of cardiovascular and inflammatory diseases and inflammatory disorders.
Treatment of iron storage disorders.
Treatment of aging and neurodegenerative diseases.
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