- TYK2 INHIBITORS AND USES THEREOF
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Described herein are compounds that are useful in treating a TYK2-mediated disorder. In some embodiments, the TYK2-mediated disorder is an autoimmune disorder, an inflammatory disorder, a proliferative disorder, an endocrine disorder, a neurological disorder, or a disorder associated with transplantation.
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Paragraph 00242; 00342
(2020/09/27)
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- Identification of 2-Imidazopyridine and 2-Aminopyridone Purinones as Potent Pan-Janus Kinase (JAK) Inhibitors for the Inhaled Treatment of Respiratory Diseases
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Janus kinases (JAKs) have a key role in regulating the expression and function of relevant inflammatory cytokines involved in asthma and chronic obstructive pulmonary disease. Herein are described the design, synthesis, and pharmacological evaluation of a series of novel purinone JAK inhibitors with profiles suitable for inhaled administration. Replacement of the imidazopyridine hinge binding motif present in the initial compounds of this series with a pyridone ring resulted in the mitigation of cell cytotoxicity. Further systematic structure-activity relationship (SAR) efforts driven by structural biology studies led to the discovery of pyridone 34, a potent pan-JAK inhibitor with good selectivity, long lung retention time, low oral bioavailability, and proven efficacy in the lipopolysaccharide-induced rat model of airway inflammation by the inhaled route.
- Bach, Jordi,Eastwood, Paul,González, Jacob,Gómez, Elena,Alonso, Juan Antonio,Fonquerna, Silvia,Lozoya, Estrella,Orellana, Adela,Maldonado, Mónica,Calaf, Elena,Albertí, Joan,Pérez, Juan,Andrés, Ana,Prats, Neus,Carre?o, Cristina,Calama, Elena,De Alba, Jorge,Calbet, Marta,Miralpeix, Montserrat,Ramis, Isabel
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supporting information
p. 9045 - 9060
(2019/11/03)
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- Discovery of (E)-3-((styrylsulfonyl)methyl)pyridine and (E)-2-((styrylsulfonyl)methyl)pyridine derivatives as anticancer agents: Synthesis, structure-activity relationships, and biological activities
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ON01910.Na is a highly effective anticancer agent that induces mitotic arrest and apoptosis. Clinical studies with ON01910 in cancer patients have shown efficacy along with an impressive safety profile. While ON01910 is highly active against cancer cells,
- Lu, Tiangong,Goh, Aik Wye,Yu, Mingfeng,Adams, Julian,Lam, Frankie,Teo, Theodosia,Li, Peng,Noll, Ben,Zhong, Longjin,Diab, Sarah,Chahrour, Osama,Hu, Anran,Abbas, Abdullahi Y.,Liu, Xiangrui,Huang, Shiliang,Sumby, Christopher J.,Milne, Robert,Midgley, Carol,Wang, Shudong
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p. 2275 - 2291
(2014/04/17)
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- Pyridin-2(1H)-one derivatives useful as medicaments for the treatment of myeloproliferative disorders, transplant rejection, immune-mediated and inflammatory diseases
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New pyridin-2(1h)-one derivatives having the chemical structure of formula (I) are disclosed; as well as process for their preparation, pharmaceutical compositions comprising them and their use in therapy as inhibitors of Janus Kinases (JAK).
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Page/Page column 23
(2012/12/13)
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- PYRIDIN-2 (1H) -ONE DERIVATIVES USEFUL AS MEDICAMENTS FOR THE TREATMENT OF MYELOPROLIFERATIVE DISORDERS, TRANSPLANT REJECTION, IMMUNE-MEDIATED AND INFLAMMATORY DISEASES
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Compoundshaving the chemical structure of formula (I) are disclosed; as well as process for theirpreparation, pharmaceutical compositions comprising them and their use in therapy as inhibitors of Janus Kinases (JAK).
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Page/Page column 68
(2012/12/13)
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- COMPOUNDS FOR TREATING PROLIFERATIVE DISORDERS
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.A compound of formula (I) or a pharmaceutically acceptable salt or solvate or physiologically hydrolysable, solubilising or immobilisable derivative thereof; wherein: any one or two of X·,, X2 and X3 is a N atom and the remaining two or one of X1, X2 and
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- Metallation in connection with cross-coupling reactions. Coupling of hindered aryls for the synthesis of 4-phenylpyridines as part of Streptonigrin and Lavendamycin analogues
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The synthesis of the C-D ring system of Streptonigrin and Lavendamycln alkaloid analogues by cross-coupling under Suzuki's conditions has been studied. Steric hindrance is the main problem. It has been solved either by using strong bases or working in a sealed tube under pressure.
- Godard,Rocca,Pomel,Thomas-Dit-Dumont,Rovera,Thaburet,Marsais,Queguiner
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