Discovery of the macrocycle (9E)-15-(2-(pyrrolidin-1-yl)ethoxy)-7,12,25-trioxa-19,21,24-triaza-tetracyclo[18.3.1.1(2,5).1(14,18)]hexacosa-1(24),2,4,9,14(26),15,17,20,22-nonaene (SB1578), a potent inhibitor of janus kinase 2/fms-like tyrosine kinase-3 (JAK2/FLT3) for the treatment of rheumatoid arthr

@article{William2012DiscoveryOT,
  title={Discovery of the macrocycle (9E)-15-(2-(pyrrolidin-1-yl)ethoxy)-7,12,25-trioxa-19,21,24-triaza-tetracyclo[18.3.1.1(2,5).1(14,18)]hexacosa-1(24),2,4,9,14(26),15,17,20,22-nonaene (SB1578), a potent inhibitor of janus kinase 2/fms-like tyrosine kinase-3 (JAK2/FLT3) for the treatment of rheumatoid arthr},
  author={A. William and Angeline Lee and A. Poulsen and K. Goh and B. Madan and S. Hart and Evelyn Tan and Haishan Wang and Harish Nagaraj and Dizhong Chen and C. Lee and E. Sun and R. Jayaraman and Mohammad Khalid Pasha and K. Ethirajulu and J. Wood and B. Dymock},
  journal={Journal of medicinal chemistry},
  year={2012},
  volume={55 6},
  pages={
          2623-40
        }
}
Herein, we describe the synthesis and SAR of a series of small molecule macrocycles that selectively inhibit JAK2 kinase within the JAK family and FLT3 kinase. Following a multiparameter optimization of a key aryl ring of the previously described SB1518 (pacritinib), the highly soluble 14l was selected as the optimal compound. Oral efficacy in the murine collagen-induced arthritis (CIA) model for rheumatoid arthritis (RA) supported 14l as a potential treatment for autoimmune diseases and… Expand
Recent advances in FLT3 inhibitors for acute myeloid leukemia.
Ensemble docking-based virtual screening yields novel spirocyclic JAK1 inhibitors.
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