Discovery of triazines as selective PDE4B versus PDE4D inhibitors.

@article{Hagen2014DiscoveryOT,
  title={Discovery of triazines as selective PDE4B versus PDE4D inhibitors.},
  author={T. H. J. J. van der Hagen and Xuesheng Mo and Alex B. Burgin and David L Fox and Zheng Zhang and Mark E Gurney},
  journal={Bioorganic & medicinal chemistry letters},
  year={2014},
  volume={24 16},
  pages={4031-4}
}
In this study we report a series of triazine derivatives that are potent inhibitors of PDE4B. We also provide a series of structure activity relationships that demonstrate the triazine core can be used to generate subtype selective inhibitors of PDE4B versus PDE4D. A high resolution co-crystal structure shows that the inhibitors interact with a C-terminal regulatory helix (CR3) locking the enzyme in an inactive 'closed' conformation. The results show that the compounds interact with both… CONTINUE READING