Identification of 4-(2-furanyl)pyrimidin-2-amines as Janus kinase 2 inhibitors

  • Bioorg Med Chem. 2017 Jan 1;25(1):75-83. doi: 10.1016/j.bmc.2016.10.011.
Yazhou Wang  1 ,  Wei Huang  2 ,  Minhang Xin  3 ,  Pan Chen  4 ,  Li Gui  4 ,  Xinge Zhao  4 ,  Feng Tang  4 ,  Jia Wang  4 ,  Fei Liu  5
Affiliations
  • 1. Key Laboratory of Pesticide and Chemical Biology, Ministry of Education, College of Chemistry, Central China Normal University, Wuhan 430079, PR China; Jiangsu Simcere Pharmaceutical Co. Ltd, Jiangsu Key Laboratory of Molecular Targeted Antitumor Drug Research, No 699-18, Xuan Wu District, Nanjing 210042, PR China. Electronic address: [email protected].
  • 2. Key Laboratory of Pesticide and Chemical Biology, Ministry of Education, College of Chemistry, Central China Normal University, Wuhan 430079, PR China; Jiangsu Simcere Pharmaceutical Co. Ltd, Jiangsu Key Laboratory of Molecular Targeted Antitumor Drug Research, No 699-18, Xuan Wu District, Nanjing 210042, PR China. Electronic address: [email protected].
  • 3. Department of Medicinal Chemistry, School of Pharmacy, Health Science Center, Xi'an Jiaotong University, No 76, Yanta West Road, Xi'an 710061, PR China.
  • 4. Jiangsu Simcere Pharmaceutical Co. Ltd, Jiangsu Key Laboratory of Molecular Targeted Antitumor Drug Research, No 699-18, Xuan Wu District, Nanjing 210042, PR China.
  • 5. Jiangsu Simcere Pharmaceutical Co. Ltd, Jiangsu Key Laboratory of Molecular Targeted Antitumor Drug Research, No 699-18, Xuan Wu District, Nanjing 210042, PR China. Electronic address: [email protected].
PMID: 27771180 DOI: 10.1016/j.bmc.2016.10.011
Abstract

Janus kinases inhibitor is considered to have therapeutic potential for the treatment of oncology and immune-inflammatory diseases. Two series of 4-(2-benzofuranyl)pyrimidin-2-amine and 4-(4,5,6,7-tetrahydrofuro[3,2-c]pyridin-2-yl)pyrimidin-2-amine derivatives have been designed and synthesized. Primary SAR studies resulted in the discovery of a novel class of 4,5,6,7-tetrahydrofuro[3,2-c]pyridine based JAK2 inhibitors with higher potency (IC50 of 0.7nM) and selectivity (>30 fold) to JAK3 kinase than tofacitinib.

Keywords
4,5,6,7-Tetrahydro-furo[3,2-c]pyridine; 4-(2-Furanyl)pyrimidin-2-amine; JAK2 inhibitor; Kinase selectivity.
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