252853-22-8Relevant academic research and scientific papers
Discovery of CP-690,550: A potent and selective janus kinase (JAK) inhibitor for the treatment of autoimmune diseases and organ transplant rejection
Flanagan, Mark E.,Blumenkopf, Todd A.,Brissette, William H.,Brown, Matthew F.,Casavant, Jeffrey M.,Shang-Poa, Chang,Doty, Jonathan L.,Elliott, Eileen A.,Fisher, Michael B.,Hines, Michael,Kent, Craig,Kudlacz, Elizabeth M.,Lillie, Brett M.,Magnuson, Kelly S.,McCurdy, Sandra P.,Munchhof, Michael J.,Perry, Bret D.,Sawyer, Perry S.,Strelevitz, Timothy J.,Subramanyam, Chakrapani,Sun, Jianmin,Whipple, David A.,Changelian, Paul S.
experimental part, p. 8468 - 8484 (2011/02/26)
There is a critical need for safer and more convenient treatments for organ transplant rejection and autoimmune disorders such as rheumatoid arthritis. Janus tyrosine kinases (JAK1, JAK3) are expressed in lymphoid cells and are involved in the signaling of multiple cytokines important for various T cell functions. Blockade of the JAK1/JAK3-STAT pathway with a small molecule was anticipated to provide therapeutic immunosuppression/immunomodulation. The Pfizer compound library was screened against the catalytic domain of JAK3 resulting in the identification of a pyrrolopyrimidine-based series of inhibitors represented by CP-352,664 (2a). Synthetic analogues of 2a were screened against the JAK enzymes and evaluated in an IL-2 induced T cell blast proliferation assay. Select compounds were evaluated in rodent efficacy models of allograft rejection and destructive inflammatory arthritis. Optimization within this chemical series led to identification of CP-690,550 1, a potential first-in-class JAK inhibitor for treatment of autoimmune diseases and organ transplant rejection.
Pyrrolo[2,3-d]pyrimidine compounds
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, (2008/06/13)
A compound of the formula wherein R1, R2 and R3 are as defined above, which are inhibitors of the enzyme protein tyrosine kinases such as Janus Kinase 3 and as such are useful therapy as immunosuppressive agents for organ transplants, lupus, multiple sclerosis, rheumatoid arthritis, psoriasis, Type I diabetes and complications from diabetes, cancer, asthma, atopic dermatitis, autoimmune thyroid disorders, ulcerative colitis, Crohn's disease, Alzheimer's disease, Leukemia and other autoimmune diseases.
