Investigation of aminopyridiopyrazinones as PDE5 inhibitors: Evaluation of modifications to the central ring system

Bioorg Med Chem Lett. 2009 Aug 1;19(15):4092-6. doi: 10.1016/j.bmcl.2009.06.004. Epub 2009 Jun 6.

Abstract

Efforts to improve the potency and physical properties of the aminopyridiopyrazinone class of PDE5 inhibitors through modification of the core ring system are described. Five new ring systems are evaluated and features that impart improved potency and improved solubility are delineated.

MeSH terms

  • Administration, Oral
  • Aminopyridines / chemical synthesis*
  • Aminopyridines / pharmacology
  • Animals
  • Chemistry, Pharmaceutical / methods
  • Cyclic GMP / chemistry
  • Cyclic Nucleotide Phosphodiesterases, Type 5 / chemistry
  • Drug Design
  • Humans
  • Hydrogen-Ion Concentration
  • Hypertension / drug therapy
  • Microsomes / drug effects
  • Models, Chemical
  • Phosphodiesterase 5 Inhibitors*
  • Phosphodiesterase Inhibitors / chemical synthesis*
  • Phosphodiesterase Inhibitors / pharmacology
  • Pyrazines / chemical synthesis*
  • Pyrazines / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Solubility

Substances

  • Aminopyridines
  • Phosphodiesterase 5 Inhibitors
  • Phosphodiesterase Inhibitors
  • Pyrazines
  • Cyclic Nucleotide Phosphodiesterases, Type 5
  • Cyclic GMP