In 2018,Journal of Medicinal Chemistry included an article by Vazquez, Michael L.; Kaila, Neelu; Strohbach, Joseph W.; Trzupek, John D.; Brown, Matthew F.; Flanagan, Mark E.; Mitton-Fry, Mark J.; Johnson, Timothy A.; TenBrink, Ruth E.; Arnold, Eric P.; Basak, Arindrajit; Heasley, Steven E.; Kwon, Soojin; Langille, Jonathan; Parikh, Mihir D.; Griffin, Sarah H.; Casavant, Jeffrey M.; Duclos, Brian A.; Fenwick, Ashley E.; Harris, Thomas M.; Han, Seungil; Caspers, Nicole; Dowty, Martin E.; Yang, Xin; Banker, Mary Ellen; Hegen, Martin; Symanowicz, Peter T.; Li, Li; Wang, Lu; Lin, Tsung H.; Jussif, Jason; Clark, James D.; Telliez, Jean-Baptiste; Robinson, Ralph P.; Unwalla, Ray. Related Products of 90213-66-4. The article was titled 《Identification of N-{cis-3-[Methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}propane-1-sulfonamide (PF-04965842): A Selective JAK1 Clinical Candidate for the Treatment of Autoimmune Diseases》. The information in the text is summarized as follows:
Janus kinases (JAKs) are intracellular tyrosine kinases that mediate the signaling of numerous cytokines and growth factors involved in the regulation of immunity, inflammation, and hematopoiesis. As JAK1 pairs with JAK2, JAK3, and TYK2, a JAK1-selective inhibitor would be expected to inhibit many cytokines involved in inflammation and immune function while avoiding inhibition of the JAK2 homodimer regulating erythropoietin and thrombopoietin signaling. The authors’ efforts began with tofacitinib, an oral JAK inhibitor approved for the treatment of rheumatoid arthritis. Through modification of the 3-aminopiperidine linker in tofacitinib, the authors discovered highly selective JAK1 inhibitors with nanomolar potency in a human whole blood assay. Improvements in JAK1 potency and selectivity were achieved via structural modifications suggested by x-ray crystallog. anal. After demonstrating efficacy in a rat adjuvant-induced arthritis (rAIA) model, PF-04965842 (25) was nominated as a clin. candidate for the treatment of JAK1-mediated autoimmune diseases.2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4Related Products of 90213-66-4) was used in this study.
2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4) belongs to pyrimidine. The pyrimidine ring system has wide occurrence in nature as substituted and ring fused compounds and derivatives, including the nucleotides cytosine, thymine and uracil, thiamine (vitamin B1) and alloxan. Related Products of 90213-66-4
Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia