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Discovery and profiling of a selective and efficacious Syk inhibitor
Gebhard Thoma1, Alexander B Smith, Maurice J van Eis
1Global Discovery Chemistry, ‡Analytical Sciences & Imaging, §Autoimmunity, Transplantation and Inflammation Research, Novartis Institutes for Biomedical Research , 4056 Basel, Switzerland.
Abstract:
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.
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