Global Discovery Chemistry, ‡Analytical Sciences & Imaging, §Autoimmunity, Transplantation and Inflammation Research, Novartis Institutes for Biomedical Research , 4056 Basel, Switzerland.
J Med Chem. 2015 Feb 26;58(4):1950-63. doi: 10.1021/jm5018863. Epub 2015 Feb 9.
We describe the discovery of selective and potent Syk inhibitor 11, which exhibited favorable PK profiles in rat and dog and was found to be active in a collagen-induced arthritis model in rats. Compound 11 was selected for further profiling, but, unfortunately, in GLP toxicological studies it showed liver findings in rat and dog. Nevertheless, 11 could become a valuable tool compound to investigate the rich biology of Syk in vitro and in vivo.
我们描述了选择性和强效的 Syk 抑制剂 11 的发现，它在大鼠和狗中表现出良好的 PK 特征，并在大鼠胶原诱导性关节炎模型中被发现具有活性。化合物 11 被选为进一步研究，但不幸的是，在 GLP 毒理学研究中，它在大鼠和狗中显示出肝脏发现。尽管如此，11 仍可能成为一种有价值的工具化合物，用于在体外和体内研究 Syk 的丰富生物学。
