Discovery of selective PDE4B inhibitors

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Abstract

In this study the first PDE4B selective inhibitor is described. Optimization of lead 2-arylpyrimidine derivatives afforded a series of potent PDE4B inhibitors with >100-fold selectivity over the PDE4D isozyme. With a good pharmacokinetic profile, a selected compound exhibited potent anti-inflammatory effects in vivo and showed less emesis compared with Cilomilast.

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Acknowledgments

The authors thank the analytical groups in the Research Center, Asahi Kasei Pharma Corporation for analytical and spectroscopic data. The authors thank Naoko Yamaguchi for biological evaluation.

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