Triazine derivatives as interferon gamma inhibitors: The present invention relates to interferon-gamma (IFN-γ) inhibitors, and their utility in treating or controlling diseases that can be treated or controlled through inhibition of IFN-γ production, such as Alzheimer's disease, prion diseases, multiple sclerosis, epilepsy, rheumatoid arthritis, inflammatory bowel disease, uveitis, autoimmune skin diseases, psoriasis, Sjögren's syndrome, Crohn's disease, and type 1 diabetes mellitus. The compounds are of Formula 1, 2 3, or are solvates, tautomers, or pharmaceutically acceptable salts thereof; (I), (II), (III) in which: A is an aromatic ring selected from; i. a phenyl ring substituted with up to five substituents, each independently selected from halogen atoms, haloalkyl groups having from 1 to 4 carbon atoms, alkoxy groups having from 1 to 4 carbon atoms, and haloalkoxy groups having from 1 to 4 carbon atoms; ii. a thiophene ring optionally substituted with up to three substituents each selected independently from halogen atoms, alkyl groups having from 1 to 4 carbon atoms, haloalkyl groups having from 1 to 4 carbon atoms, alkoxy groups having from 1 to 4 carbon atoms and haloalkoxy groups having from 1 to 4 carbon atoms; and iii. a C(Rd)3 group, wherein each Rd is independently selected from hydrogen, alkyl groups having from 1 to 4 carbon atoms, haloalkyl groups having from 1 to 4 carbon atoms, alkoxy groups having from 1 to 4 carbon atoms, haloalkoxy groups having from 1 to 4 carbon atoms, and phenyl rings optionally substituted with up to five substituents, each independently selected from halogen atoms, alkyl groups having from 1 to 4 carbon atoms, haloalkyl groups having from 1 to 4 carbon atoms, alkoxy groups having from 1 to 4 carbon atoms, and haloalkoxy groups having from 1 to 4 carbon atoms, cycloalkyl groups having from 3 to 8 carbon atoms, halocycloalkyl groups having from 3 to 8 carbon atoms, and wherein at least one Rd is an optionally substituted phenyl ring; Ra is selected from hydrogen, haloalkyl groups having from 1 to 4 carbon atoms, and alkyl-alkoxy groups having from 1 to 6 carbon atoms that are optionally substituted with one or more halogen atoms, with the proviso that when A is a phenyl ring comprising one or more directly bound halogen substituents, the compound is of Formula 2 or Formula 3, and Ra is not hydrogen; and each Rb is independently selected from hydrogen, and alkyl groups having from 1 to 4 carbon atoms, and haloalkyl groups having from 1 to 4 carbon atoms.
- Submitting institution
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University of Greenwich
- Unit of assessment
- 8 - Chemistry
- Output identifier
- 16252
- Type
- F - Patent/ published patent application
- Patent registration number
- WO 2016/109978 A1
- Month
- -
- Year
- 2016
- URL
-
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- Supplementary information
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- Request cross-referral to
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- Output has been delayed by COVID-19
- No
- COVID-19 affected output statement
- -
- Forensic science
- No
- Criminology
- No
- Interdisciplinary
- No
- Number of additional authors
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0
- Research group(s)
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-
- Proposed double-weighted
- No
- Reserve for an output with double weighting
- No
- Additional information
- This patent relates to the invention of certain novel orally bioavailable triazine compounds. These compounds initially arose from a previous screen of compounds for voltage gated sodium channel blocking activity. Certain voltage gated sodium channels are now known to have a role in immune system function apart from being targets in neurodegenerative processes and pain perception. Compounds within this triazine series were subsequently found to act as inhibitors of the pro-inflammatory mediator Interferon-gamma, and investigative work has now greatly expanded on this initial discovery to study many other pro-inflammatory cytokines. Key molecules within this patent have been found to potently inhibit the production of other pro-inflammatory cytokine mediators (apart from Interferon-gamma), particularly Interleukin-1-beta, Interleukin-6 and Interleukin-17.
Inflammatory mediators including Interferon-gamma, drive inflammatory processes in autoimmune diseases such as multiple sclerosis, psoriasis, Rheumatoid arthritis and Crohn's disease. These novel patented compounds which suppress pro-inflammatory cytokine expression therefore have the potential as new orally acting therapeutic agents in the treatment or control of the disease/disorders mentioned above. Inflammatory mediators, particularly Interferon-gamma, Interleukin-1-beta and Interleukin-6 have also been identified as culprits in the Cytokine Storm inflammatory process following infection by the SARSCoV-2/Covid 19 virus, in sepsis and following influenza infection. Current treatments are mainly monoclonal antibody injectable biologics targeted to an individual inflammatory mediator. The novel key compounds protected in this patent offer the advantage of being orally active agents, are pharmacologically controllable and inhibit relevant pro-inflammatory mediators in one agent. Additional extensive data on these compounds has been reported in numerous pharmaceutical industry networking IN-PART briefing sheets for collaboration with the Pharma industry. Subsequent 2020 GB patents filed are "Cytokine Storm" and "Interleukin Inhibitors", and there is active interest in these agents from Pharma and Government (US and UK).
- Author contribution statement
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- Non-English
- No
- English abstract
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