Synthesis and SAR of tetracyclic pyrroloquinolones as phosphodiesterase 5 inhibitors

Bioorg Med Chem. 2004 Mar 15;12(6):1505-15. doi: 10.1016/j.bmc.2003.12.044.

Abstract

The synthesis of the fused tetracyclic pyrroloquinolones 9a-i in four steps is described. The PDE5 inhibitory activities of these compounds, their selectivities against PDE1, PDE2, PDE3, PDE4 and PDE6, the preclinical pharmacokinetic assessments and the in vivo efficacy in increasing intracavernosal pressure are presented and discussed.

MeSH terms

  • 3',5'-Cyclic-GMP Phosphodiesterases
  • Animals
  • Cyclic Nucleotide Phosphodiesterases, Type 5
  • Dogs
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Isoenzymes
  • Phosphodiesterase Inhibitors / chemical synthesis*
  • Phosphodiesterase Inhibitors / pharmacology
  • Phosphoric Diester Hydrolases / chemistry*
  • Piperazines / administration & dosage
  • Purines
  • Quinolones / chemical synthesis*
  • Quinolones / pharmacology
  • Sildenafil Citrate
  • Structure-Activity Relationship
  • Sulfones

Substances

  • Enzyme Inhibitors
  • Isoenzymes
  • Phosphodiesterase Inhibitors
  • Piperazines
  • Purines
  • Quinolones
  • Sulfones
  • Sildenafil Citrate
  • Phosphoric Diester Hydrolases
  • 3',5'-Cyclic-GMP Phosphodiesterases
  • Cyclic Nucleotide Phosphodiesterases, Type 5
  • PDE5A protein, human