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.; Schonbrunn, Ernst published an article in 2021. The article was titled 《Structural Insights into JAK2 Inhibition by Ruxolitinib, Fedratinib, and Derivatives Thereof》, and you may find the article in Journal of Medicinal Chemistry.Synthetic Route of C6H3Cl2N3 The information in the text is summarized as follows:
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 mol. inhibitors for this patient population. Ruxolitinib and fedratinib have been approved for use in MPN patients, while baricitinib, an achiral analog 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 methodol. 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 biochem. 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. The results came from multiple reactions, including the reaction of 2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4Synthetic Route of C6H3Cl2N3)
2,4-Dichloro-7H-pyrrolo[2,3-d]pyrimidine(cas: 90213-66-4) belongs to pyrimidine. Pyrimidine nucleotide derivatives have a wide range of biological applications. For example, pyrimidine derivatives are useful in DNA repair studies involving cancer and epigenetics. Synthetic Route of C6H3Cl2N3
Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia