- Discovery of a Highly Selective JAK2 Inhibitor, BMS-911543, for the Treatment of Myeloproliferative Neoplasms
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JAK2 kinase inhibitors are a promising new class of agents for the treatment of myeloproliferative neoplasms and have potential for the treatment of other diseases possessing a deregulated JAK2-STAT pathway. X-ray structure and ADME guided refinement of C
- Wan, Honghe,Schroeder, Gretchen M.,Hart, Amy C.,Inghrim, Jennifer,Grebinski, James,Tokarski, John S.,Lorenzi, Matthew V.,You, Dan,Mcdevitt, Theresa,Penhallow, Becky,Vuppugalla, Ragini,Zhang, Yueping,Gu, Xiaomei,Iyer, Ramaswamy,Lombardo, Louis J.,Trainor, George L.,Ruepp, Stefan,Lippy, Jonathan,Blat, Yuval,Sack, John S.,Khan, Javed A.,Stefanski, Kevin,Sleczka, Bogdan,Mathur, Arvind,Sun, Jung-Hui,Wong, Michael K.,Wu, Dauh-Rurng,Li, Peng,Gupta, Anuradha,Arunachalam,Pragalathan, Bala,Narayanan, Sankara,Nanjundaswamy,Kuppusamy, Prakasam,Purandare, Ashok V.
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- Ni-Catalyzed C-H Functionalization in the Formation of a Complex Heterocycle: Synthesis of the Potent JAK2 Inhibitor BMS-911543
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BMS-911543 is a complex pyrrolopyridine investigated as a potential treatment for myeloproliferative disorders. The development of a short and efficient synthesis of this molecule is described. During the course of our studies, a Ni-mediated C-N bond formation was invented, which enabled the rapid construction of the highly substituted 2-aminopyridine core. The synthesis of this complex, nitrogen-rich heterocycle was accomplished in only eight steps starting from readily available materials.
- Fitzgerald, Monica A,Soltani, Omid,Wei, Carolyn,Skliar, Dimitri,Zheng, Bin,Li, Jun,Albrecht, Jacob,Schmidt, Michael,Mahoney, Michelle,Fox, Richard J.,Tran, Kristy,Zhu, Keming,Eastgate, Martin D.
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- C-H Arylation in the Formation of a Complex Pyrrolopyridine, the Commercial Synthesis of the Potent JAK2 Inhibitor, BMS-911543
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The development of an improved short and efficient commercial synthesis of the JAK2 inhibitor, a complex pyrrolopyridine, BMS-911543, is described. During the discovery and development of this synthesis, a Pd-catalyzed C-H functionalization was invented which enabled the rapid union of the key pyrrole and imidazole fragments. The synthesis of this complex, nitrogen-rich heterocycle was accomplished in only six steps (longest linear sequence) from readily available materials.
- Fox, Richard J.,Cuniere, Nicolas L.,Bakrania, Lopa,Wei, Carolyn,Strotman, Neil A.,Hay, Michael,Fanfair, Dayne,Regens, Christopher,Beutner, Gregory L.,Lawler, Michael,Lobben, Paul,Soumeillant, Maxime C.,Cohen, Benjamin,Zhu, Keming,Skliar, Dimitri,Rosner, Thorsten,Markwalter, Chester E.,Hsiao, Yi,Tran, Kristy,Eastgate, Martin D.
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- PROCESS FOR THE PREPARATION OF N,N-DICYCLOPROPYL-4-(1,5-DIMETHYL-1H-PYRAZOL-3-YLAMINO)-6-ETHYL-1-METHYL-1,6-DIHYDROIMIDAZO[4,5-d]PYRROLO[2,3-b]PYRIDINE-7-CARBOXAMIDE
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The invention relates to an improved process for synthesizing N,N-dicyclopropyl-4-(1,5-dimethyl-1H-pyrazol-3-ylamino)-6-ethyl-1-methyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxamide of the formula: (I) Compound (I) is currently in clinical trials for the treatment of myeloproliferative disorders, such as polycythaemia vera, thrombocythaemia and primary myelofibrosis.
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- JAK2 INHIBITORS AND THEIR USE FOR THE TREATMENT OF MYELOPROLIFERATIVE DISEASES AND CANCER
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The present invention provides compounds of formula (I) and pharmaceutically acceptable salts thereof. The formula (I) compounds inhibit tyrosine kinase activity of JAK2, thereby making them useful as antiproliferative agents for the treatment of cancer and other diseases.
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