PDE5 inhibitors: An original access to novel potent arylated analogues of tadalafil

Bioorg Med Chem Lett. 2007 Feb 1;17(3):789-92. doi: 10.1016/j.bmcl.2006.10.069. Epub 2006 Oct 27.


A method to access totally new analogues of tadalafil was explored. The Buchwald reaction was adapted and used to replace the methyl group of tadalafil by various aryl groups. Inhibition potencies on PDE5 of these analogues were determined and proved to be comparable to the one of tadalafil. Using the same route, compounds with the same level of activity but improved water solubility were produced by introducing a pyridine or a pyrimidine ring. This original route also opens access to new unpatented compounds.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3',5'-Cyclic-GMP Phosphodiesterases / antagonists & inhibitors*
  • Carbolines / pharmacology*
  • Catalysis
  • Copper
  • Cyclic Nucleotide Phosphodiesterases, Type 5
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacology*
  • Fluorescence Resonance Energy Transfer
  • Indicators and Reagents
  • Isomerism
  • Molecular Conformation
  • Structure-Activity Relationship
  • Tadalafil


  • Carbolines
  • Enzyme Inhibitors
  • Indicators and Reagents
  • Tadalafil
  • Copper
  • 3',5'-Cyclic-GMP Phosphodiesterases
  • Cyclic Nucleotide Phosphodiesterases, Type 5