Non-fused thiophene derivatives and their uses
Inventors
MELDRUM, Eric • DE CHASSEY, BENOÎT • MACHIN, PETER • Malagu, Karine Fabienne • WINSHIP, PAUL COLIN MICHAEL • Chambers, Mark • Knight, Jamie David • LANARO, Roberta
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-11840527-B2
Publication Date
2023-12-12
Expiration Date
Abstract
The present invention relates to a new class of non-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 compounds of formula (I), including stereoisomers and pharmaceutical salts thereof. The compounds define R1 as a 3-10 membered saturated ring selected from cycloalkyl and bridged carbocyclyl, optionally substituted by halogen and/or a (C1-C6)alkyl, and define R2 as hydrogen, a (C1-C6)alkyl, or halogen. R4 is —COOH and R5 is hydrogen.
R3 is a phenyl optionally substituted by morpholinyl, —NH-tetrahydropyranyl, —NH—(C1-C6)alkyl optionally substituted by tetrahydropyranyl or a (C1-C6)alkyloxy, an azetidinyl optionally substituted by a (C1-C6)alkyloxy, a (C1-C6)alkyl optionally substituted by at least one halogen, halogen, and a (C1-C6)alkyloxy optionally substituted by at least one halogen. The disclosure further provides multiple specific thiophene-3-carboxylic acid derivatives as Compound # examples consistent with the formula (I) framework.
The document also provides chemical structure depictions for additional enumerated thiophene-3-carboxylic acid derivatives sharing a thiophene-3-carboxylic acid core and an amide linkage of the form —NH—C(=O)— to a substituted anilide/aryl group. Across the listed compounds, the shared scaffold is maintained while substituent patterns are diversified, including halogen substituents such as F and Cl, heterocycles described as morpholine-like and tetrahydropyran-like groups, and different alkyl substituents.
Claims Coverage
The claims coverage centers on one independent compound claim defining formula (I) with five substituent positions and included stereoisomers or pharmaceutical salts, together with a therapeutic use claim. In total, the independent claims present two core inventive features: the defined compound class and the disease-treatment method.
Formula I compound with defined substituents
A compound of formula (I) wherein R1 is a 3-10 membered saturated ring selected from cycloalkyl and bridged carbocyclyl optionally substituted by halogen and/or a (C1-C6)alkyl; R2 is hydrogen, a (C1-C6)alkyl, or halogen; R3 is a phenyl optionally substituted by morpholinyl, —NH-tetrahydropyranyl, —NH—(C1-C6)alkyl optionally substituted by tetrahydropyranyl or a (C1-C6)alkyloxy, an azetidinyl optionally substituted by a (C1-C6)alkyloxy, a (C1-C6)alkyl optionally substituted by at least one halogen, halogen, and a (C1-C6)alkyloxy optionally substituted by at least one halogen; R4 is —COOH; and R5 is hydrogen, or a stereoisomer or pharmaceutical salt thereof.
Enumerated specific formula I members
A compound according to claim 1 selected from an explicit listed group of specific substituted thiophene-3-carboxylic acid derivatives identified as Compound #9, #10, #11, #12, #13, #14, #15, #18, #25, #26, #27, #29, #35, #37, #39, #48, #54, #59, #60, #61, #62, #63, #66, #71, #87, #88, #90, #97, #98, #99, #106, #107, #108, #111, #112, and #115.
Treating influenza or lung cancer by administering the compound
A method of treating influenza virus A infection, influenza virus B infection, influenza virus C infection, or lung cancer by administering to a subject in need thereof the compound of formula (I).
Overall, the claims cover a formula (I) compound class with defined substituent options and a therapeutic method using those compounds for influenza virus A/B/C infections or lung cancer.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Treatment of influenza virus A infection, influenza virus B infection, influenza virus C infection, or lung cancer by administering a compound according to formula (I).
Treatment of influenza virus A infection, specifically an H1N1 influenza virus infection.
Treatment of lung cancer.
Antiviral activity against H1N1 using A549 cells.
Cytotoxicity and antitumoral evaluation.
Mechanistic assessment of NEET proteins, including Fe-S cluster stability.
NF-κB inhibition assessed using an NF-κB reporter/NanoLuciferase format after TNF-β1 stimulation.
Providing a pharmaceutical composition including a compound according to claim 1 together with an acceptable pharmaceutical excipient.
Interested in licensing this patent?