论文信息 - 2-Amino-aryl-7-aryl-benzoxazoles as potent, selective and orally available JAK2 inhibitors.

2-Amino-aryl-7-aryl-benzoxazoles as potent, selective and orally available JAK2 inhibitors.

A series of novel benzoxazole derivatives has been designed and shown to exhibit attractive JAK2 inhibitory profiles in biochemical and cellular assays, capable of delivering compounds with favorable PK properties in rats. Synthesis and structure-activity relationship data are also provided.

[1] Sandra A. Moore,et al. Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis. , 2005, Cancer cell.

[2] Mauno Vihinen,et al. Autoinhibition of Jak2 tyrosine kinase is dependent on specific regions in its pseudokinase domain. , 2003, Molecular biology of the cell.

[3] A. Andres,et al. JAK2, a third member of the JAK family of protein tyrosine kinases. , 1992, Oncogene.

[4] Stefan N. Constantinescu,et al. A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera , 2005, Nature.

[5] J. Pierre,et al. JAK/STAT signal transduction: regulators and implication in hematological malignancies. , 2006, Biochemical pharmacology.

[6] O. Silvennoinen,et al. The Janus kinases (Jaks) , 2004, Genome Biology.

[7] J. Caldwell,et al. Design and synthesis of 7H-pyrrolo[2,3-d]pyrimidines as focal adhesion kinase inhibitors. Part 1. , 2006, Bioorganic & medicinal chemistry letters.

[8] H. Deeg,et al. International Working Group (IWG) consensus criteria for treatment response in myelofibrosis with myeloid metaplasia, for the IWG for Myelofibrosis Research and Treatment (IWG-MRT). , 2006, Blood.

[9] W. Vainchenker,et al. A unique activating mutation in JAK2 (V617F) is at the origin of polycythemia vera and allows a new classification of myeloproliferative diseases. , 2005, Hematology. American Society of Hematology. Education Program.