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, 26 (22), 5562-5567

Synthesis and Optimization of furano[3,2-d]pyrimidines as Selective Spleen Tyrosine Kinase (Syk) Inhibitors

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Synthesis and Optimization of furano[3,2-d]pyrimidines as Selective Spleen Tyrosine Kinase (Syk) Inhibitors

Michael Hoemann et al. Bioorg Med Chem Lett.

Abstract

A series of furano[3,2-d]pyrimidine Syk inhibitors were synthesized and optimized for their enzyme potency and selectivity versus other kinases. In addition, ADME properties were assessed and compounds were prepared with optimized profiles for in vivo experiments. Compound 23 was identified as having acceptable pharmacokinetic properties and demonstrated efficacy in a rat collagen induced arthritis model.

Keywords: Furano[3,2-d]pyrimidine; Kinase inhibitor; Rheumatoid arthritis; Spleen tyrosine kinase; Syk.

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