Identification of the 5,5-dioxo-7,8-dihydro-6H-thiopyrano[3,2-d]pyrimidine derivatives as highly selective PDE4B inhibitors.

@article{Goto2014IdentificationOT,
  title={Identification of the 5,5-dioxo-7,8-dihydro-6H-thiopyrano[3,2-d]pyrimidine derivatives as highly selective PDE4B inhibitors.},
  author={Taiji Goto and Akiko Shiina and Takeshi Murata and Masato Tomii and Takanori Yamazaki and Ken-ichi Yoshida and Toshiharu Yoshino and Osamu Suzuki and Yoshitaka Sogawa and Kiyoshi Mizukami and Nana Takagi and Tomomi Yoshitomi and Maki Etori and Hiroshi Tsuchida and Tsuyoshi Mikkaichi and Naoki Nakao and Mizuki Takahashi and Hisashi Takahashi and Shigeki Sasaki},
  journal={Bioorganic & medicinal chemistry letters},
  year={2014},
  volume={24 3},
  pages={893-9}
}
A PDE4B subtype selective inhibitor is expected to have a wider therapeutic window than non-selective PDE4 inhibitors. In this Letter, two series of 7,8-dihydro-6H-thiopyrano[3,2-d]pyrimidine derivatives and 5,5-dioxo-7,8-dihydro-6H-thiopyrano[3,2-d]pyrimidine derivatives were evaluated for their PDE4B subtype selectivity using human PDE4B2 and PDE4D2 full length enzymes. To improve their PDE4B selectivity over PDE4D, we optimized the substituents on the pyrimidine ring and the side chain… CONTINUE READING