Novel Triazine Derivatives as NLRP3 Inhibitors for Treating Asthma or COPD

ACS Medicinal Chemistry Letters, Год журнала: 2025, Номер unknown

Опубликована: Янв. 24, 2025

InfoMetricsFiguresRef. ACS Medicinal Chemistry LettersASAPArticle This publication is free to access through this site. Learn More CiteCitationCitation and abstractCitation referencesMore citation options ShareShare onFacebookX (Twitter)WeChatLinkedInRedditEmailJump toExpandCollapse Patent HighlightJanuary 24, 2025Novel Triazine Derivatives as NLRP3 Inhibitors for Treating Asthma or COPDClick copy article linkArticle link copied!Ram W. Sabnis*Ram SabnisSmith, Gambrell & Russell LLP, 1105 Peachtree Street NE, Suite 1000, Atlanta, Georgia 30309, United States*E-mail: [email protected]More by Ram Sabnishttps://orcid.org/0000-0001-7289-0581Open PDFACS LettersCite this: Med. Chem. Lett. 2025, XXXX, XXX, XXX-XXXClick citationCitation copied!https://pubs.acs.org/doi/10.1021/acsmedchemlett.5c00020https://doi.org/10.1021/acsmedchemlett.5c00020Published January 2025 Publication History Received 12 2025Published online 24 2025editorialPublished American Chemical Society. available under these Terms of Use. Request reuse permissionsAbstractClick section linkSection copied!High Resolution ImageDownload MS PowerPoint SlideProvided herein are novel triazine derivatives inhibitors, pharmaceutical compositions, use such compounds in treating asthma COPD, processes preparing compounds.This licensed personal The PublicationsPublished Society Important Compound Classes TitleTriazine NumberWO 2025/003288 A1URL: https://patentscope.wipo.int/search/en/detail.jsf?docId=WO2025003288&_cid=P12-M5SZQM-50837-1 DateJanuary 2, Priority ApplicationEP 23182238.8 DateJune 29, 2023 InventorsBon, D.; Bouche, L. A.; Guba, W.; Hargrave, E.; Jaeschke, G.; Johnston, H. J.; Mesch, S. K.; Schnider, C.; Steiner, S.; Tosstorff, A. M. Assignee CompanyF. Hoffmann-La Roche AG, Switzerland, Inc., USA Disease AreaAsthma COPD Biological TargetNLRP3 SummaryThe (NOD)-like receptor (NLR) family, NOD-like protein 3 (NLRP3) inflammasome a component the inflammatory process, its aberrant activity pathogenic inherited disorders cryopyrin-associated periodic syndromes (CAPS) complex diseases multiple sclerosis, Alzheimer's disease, atherosclerosis. an intracellular signaling molecule that senses many pathogen-derived, environmental, host-derived factors. Upon activation, binds apoptosis-associated speck-like containing caspase activation recruitment domain (ASC). ASC then polymerizes form large aggregate known speck. Polymerized turn interacts with cysteine protease caspase-1 termed inflammasome.Active cytokines derived from important drivers inflammation interact other cytokine pathways shape immune response infection injury. A role central nervous system lung emerging. Furthermore, has development liver diseases, kidney aging.The present application describes series inhibitors treatment chronic obstructive pulmonary disease (COPD). Further, discloses compounds, their preparation, use, composition, treatment. DefinitionsA = -O- CH2; R1 hydroxyalkyl acetyl;R2 alkyl; n 0 1. Key Structures AssayThe THP-1 pyroptosis assay was performed. described were tested ability inhibit NLRP3. IC50 values (nM) shown following table. DataThe table below shows representative inhibition biological data obtained testing examples. ClaimsTotal claims: 16Compound 9Pharmaceutical composition 1Method 1Use compound Recent Review ArticlesSee refs (1−5).Author InformationClick copied!Corresponding AuthorRam Sabnis, Smith, States, https://orcid.org/0000-0001-7289-0581, Email: protected]NotesThe author declares no competing financial interest.ReferencesClick copied! references 5 publications. 1Beucher, L.; Gabillard-Lefort, Baris, O. R.; Mialet-Perez, J. Monoamine oxidases: missing between mitochondria diseases. Redox Biol. 2024, 77, 103393, DOI: 10.1016/j.redox.2024.103393 Google ScholarThere corresponding record reference.2Pan, M.; Yang, Jiang, Z. Inflammasomes roles autoimmune Rheumatol. Autoimmun. 4, 197– 217, 10.1002/rai2.12155 reference.3Zhou, H.; Wang, Lv, Yu, allergic diseases: mechanisms therapeutic implications. Clin. Exp. 231, 10.1007/s10238-024-01492-z reference.4Sabnis, R. Fused Bicyclic Heteroaryl Compounds COPD. 2023, 14, 895– 896, 10.1021/acsmedchemlett.3c00236 reference.5Luo, Zhuang, X.; Fu, Dong, Z.; Yi, Y.; Zhao, Hei, F. interplay macrophage glycolytic reprogramming acute injury/acute respiratory distress syndrome. Transl. e70098 10.1002/ctm2.70098 reference.Cited By Click copied!This not yet been cited publications.Download PDFFiguresReferences Get e-AlertsGet e-AlertsACS copied!https://doi.org/10.1021/acsmedchemlett.5c00020Published permissionsArticle Views-Altmetric-Citations-Learn about metrics closeArticle Views COUNTER-compliant sum full text downloads since November 2008 (both PDF HTML) across all institutions individuals. These regularly updated reflect usage leading up last few days.Citations number articles citing article, calculated Crossref daily. Find more information counts.The Altmetric Attention Score quantitative measure attention research received online. Clicking on donut icon will load page at altmetric.com additional details score social media presence given article. how calculated.Recommended Articles FiguresReferencesAbstractHigh SlideReferences There reference.

Язык: Английский

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Genetic and Epigenetic Interconnections Between Atopic Dermatitis, Allergic Rhinitis, and Rhinitis with Nasal Polyps

Allergies, Год журнала: 2025, Номер 5(2), С. 9 - 9

Опубликована: Март 27, 2025

Background: Atopic dermatitis (AD), allergic rhinitis (AR), and chronic rhinosinusitis with nasal polyps (CRSwNP) represent interconnected conditions within the spectrum of type 2 inflammatory diseases. While these share common genetic epigenetic pathways, precise molecular mechanisms remain underexplored. Methods: This review integrates latest insights on factors linking AD, AR, CRSwNP, focusing genome-wide association studies, DNA methylation patterns, histone modifications, microRNA regulation. Results: In all three conditions, including (Me) acetylation (Ac) methylation, regulate barrier-related genes, influencing disease severity. Notably, miRNAs such as miR-146a miR-155 play pivotal roles in modulating inflammation across diseases, while disease-specific contribute to airway remodeling (miR-125b miR-21 AR CRSwNP). Emerging evidence underscores role microbiome-driven inflammasome activation matrix metalloproteinases (MMP-2, MMP-9, MMP-12) perpetuating remodeling. Conclusions: The interplay between predispositions, exposomal systemic nature inflammation. A deeper understanding could lead transformative, personalized diagnostic therapeutic advancements.

Язык: Английский

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Novel Compounds as NLRP3 Inhibitors for Treating Asthma or COPD

ACS Medicinal Chemistry Letters, Год журнала: 2025, Номер 16(4), С. 538 - 539

Опубликована: Апрель 1, 2025

Provided herein are novel compounds as NLRP3 inhibitors, pharmaceutical compositions, use of such in treating asthma or COPD, and processes for preparing compounds.

Язык: Английский

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Interleukin 1β Mediates the Pathogenesis of Nasal Mucosal Epithelial Barrier Dysfunction in Allergic Rhinitis

Journal of Inflammation Research, Год журнала: 2024, Номер Volume 17, С. 9071 - 9085

Опубликована: Ноя. 1, 2024

The nasal mucosal epithelial barrier is the primary site of allergic rhinitis (AR). Interleukin-1β (IL-1β), as a crucial factor in immune inflammation, not only plays role hypersensitivity reactions but also affects digestive mucosa and skin barrier. However, IL-1β AR has been reported, this study aimed to investigate effect possible mechanisms involved.

Язык: Английский

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Extracellular vesicles of ADSCs inhibit ischemic stroke-induced pyroptosis through Gbp3 regulation: A role for the NLRP3/GSDMD signaling pathway

International Immunopharmacology, Год журнала: 2024, Номер 146, С. 113881 - 113881

Опубликована: Дек. 24, 2024

Язык: Английский

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