Discovery of a Highly Selective JAK2 Inhibitor, BMS-911543, for the Treatment of Myeloproliferative Neoplasms

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• 作者：Honghe Wan ; Gretchen M. Schroeder ; Amy C. Hart ; Jennifer Inghrim ; James Grebinski ; John S. Tokarski ; Matthew V. Lorenzi ; Dan You ; Theresa Mcdevitt ; Becky Penhallow ; Ragini Vuppugalla ; Yueping Zhang ; Xiaomei Gu ; Ramaswamy Iyer ; Louis J. Lombardo ; George L. Trainor ; Stefan Ruepp ; Jonathan Lippy ; Yuval Blat ; John S. Sack ; Javed A. Khan ; Kevin Stefanski ; Bogdan Sleczka ; Arvind Mathur ; Jung-Hui Sun ; Michael K. Wong ; Dauh-Rurng Wu ; Peng Li ; Anuradha Gupta ; P. N. Arunachalam ; Bala Pragalathan ; Sankara Narayanan ; Nanjundaswamy K.C. ; Prakasam Kuppusamy ; Ashok V. Purandare
• 刊名：ACS Medicinal Chemistry Letters
• 出版年：2015
• 出版时间：August 13, 2015
• 年：2015
• 卷：6
• 期：8
• 页码：850-855
• 全文大小：386K
• ISSN：1948-5875

文摘

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-4 heterocycles to address metabolic liability present in dialkylthiazole 1 led to the discovery of a clinical candidate, BMS-911543 (11), with excellent kinome selectivity, in vivo PD activity, and safety profile.