1146629-84-6Relevant articles and documents
Structural Insights into JAK2 Inhibition by Ruxolitinib, Fedratinib, and Derivatives Thereof
Davis, Ryan R.,Li, Baoli,Yun, Sang Y.,Chan, Alice,Nareddy, Pradeep,Gunawan, Steven,Ayaz, Muhammad,Lawrence, Harshani R.,Reuther, Gary W.,Lawrence, Nicholas J.,Sch?nbrunn, Ernst
supporting information, p. 2228 - 2241 (2021/03/01)
The discovery that aberrant activity of Janus kinase 2 (JAK2) is a driver of myeloproliferative neoplasms (MPNs) has led to significant efforts to develop small molecule inhibitors for this patient population. Ruxolitinib and fedratinib have been approved for use in MPN patients, while baricitinib, an achiral analogue of ruxolitinib, has been approved for rheumatoid arthritis. However, structural information on the interaction of these therapeutics with JAK2 remains unknown. Here, we describe a new methodology for the large-scale production of JAK2 from mammalian cells, which enabled us to determine the first crystal structures of JAK2 bound to these drugs and derivatives thereof. Along with biochemical and cellular data, the results provide a comprehensive view of the shape complementarity required for chiral and achiral inhibitors to achieve highest activity, which may facilitate the development of more effective JAK2 inhibitors as therapeutics.
PROCESSES FOR PREPARING JAK INHIBITORS AND RELATED INTERMEDIATE COMPOUNDS
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Page/Page column 91-92, (2010/08/07)
The present invention is related to processes for preparing chiral substituted pyrazolyl pyrrolo[2,3-d]pyrimidines of Formula III, and related synthetic intermediate compounds. The chiral substituted pyrazolyl pyrrolo[2,3-d]pyrimidines are useful as inhibitors of the Janus Kinase family of protein tyrosine kinases (JAKs) for treatment of inflammatory diseases, myeloproliferative disorders, and other diseases.