Discovery of selective PDE4B inhibitors

  • Bioorg Med Chem Lett. 2009 Jun 15;19(12):3174-6. doi: 10.1016/j.bmcl.2009.04.121.
Kenji Naganuma  1 ,  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
Affiliations
  • 1. Pharmaceuticals Research Center, Asahi Kasei Pharma Corporation, 632-1 Mifuku, Izunokuni-shi, Shizuoka 410-2321, Japan.
PMID: 19447034 DOI: 10.1016/j.bmcl.2009.04.121
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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