Category: pyrazoles-derivativesOn November 25, 2020 ,《Discovery of Tyrosine Kinase 2 (TYK2) Inhibitor (PF-06826647) for the Treatment of Autoimmune Diseases》 appeared in Journal of Medicinal Chemistry. The author of the article were Gerstenberger, Brian S.; Ambler, Catherine; Arnold, Eric P.; Banker, Mary-Ellen; Brown, Matthew F.; Clark, James D.; Dermenci, Alpay; Dowty, Martin E.; Fensome, Andrew; Fish, Susan; Hayward, Matthew M.; Hegen, Martin; Hollingshead, Brett D.; Knafels, John D.; Lin, David W.; Lin, Tsung H.; Owen, Dafydd R.; Saiah, Eddine; Sharma, Raman; Vajdos, Felix F.; Xing, Li; Yang, Xiaojing; Yang, Xin; Wright, Stephen W.. The article conveys some information:
Tyrosine kinase 2 (TYK2) is a member of the JAK kinase family that regulates signal transduction downstream of receptors for the IL-23/IL-12 pathways and type I interferon family, where it pairs with JAK2 or JAK1, resp. On the basis of human genetic and emerging clin. data, a selective TYK2 inhibitor provides an opportunity to treat autoimmune diseases delivering a potentially differentiated clin. profile compared to currently approved JAK inhibitors. The discovery of an ATP-competitive pyrazolopyrazinyl series of TYK2 inhibitors was accomplished through computational and structurally enabled design starting from a known kinase hinge binding motif. With understanding of PK/PD relationships, a target profile balancing TYK2 potency and selectivity over off-target JAK2 was established. Lead optimization involved modulating potency, selectivity, and ADME properties which led to the identification of the clin. candidate PF-06826647 (22). The experimental process involved the reaction of 1-Methylpyrazole(cas: 930-36-9Category: pyrazoles-derivatives)
1-Methylpyrazole(cas: 930-36-9) belongs to pyrazoles. Pyrazoles and their related multiring analogs are common elements of a wide variety of bioactive compounds. These ring structures are rare in nature. A consequence of this is that they have previously been thought to be poor moieties to include in potential new drugs. Category: pyrazoles-derivatives
Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics