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Merck

Discovery of selective PDE4B inhibitors.

Bioorganic & medicinal chemistry letters (2009-05-19)
Kenji Naganuma, Akifumi Omura, Naomi Maekawara, Masahiro Saitoh, Naoto Ohkawa, Takashi Kubota, Hiromitsu Nagumo, Toshiyuki Kodama, Masayoshi Takemura, Yuji Ohtsuka, Junji Nakamura, Ryuichi Tsujita, Koh Kawasaki, Hirotsugu Yokoi, Masashi Kawanishi
RESUMEN

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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A-33, ≥98% (HPLC)