1-(2-(2,2,2-trifluoroethoxy)ethyl-1H-pyrazolo[4,3-d]pyrimidines as potent phosphodiesterase 5 (PDE5) inhibitors

Bioorg Med Chem Lett. 2010 May 15;20(10):3125-8. doi: 10.1016/j.bmcl.2010.03.106. Epub 2010 Apr 3.

Abstract

1H-Pyrazolo[4,3-d]pyrimidines were previously disclosed as a potent second generation class of phosphodiesterase 5 (PDE5) inhibitors. This work explores the advancement of more selective and potent PDE5 inhibitors resulting from the substitution of 2-(2,2,2-trifluoroethoxy)ethyl at the 1 position in the so-called alkoxy pocket.

MeSH terms

  • Animals
  • Antihypertensive Agents / chemical synthesis
  • Antihypertensive Agents / chemistry*
  • Antihypertensive Agents / pharmacokinetics
  • Cyclic Nucleotide Phosphodiesterases, Type 5 / metabolism
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacokinetics
  • Humans
  • Microsomes, Liver / metabolism
  • Patch-Clamp Techniques
  • Phosphodiesterase 5 Inhibitors*
  • Pyrimidines / chemical synthesis
  • Pyrimidines / chemistry*
  • Pyrimidines / pharmacokinetics
  • Rats
  • Structure-Activity Relationship

Substances

  • Antihypertensive Agents
  • Enzyme Inhibitors
  • Phosphodiesterase 5 Inhibitors
  • Pyrimidines
  • Cyclic Nucleotide Phosphodiesterases, Type 5