Design, synthesis and biological activity of beta-carboline-based type-5 phosphodiesterase inhibitors

Bioorg Med Chem Lett. 2003 Apr 17;13(8):1425-8. doi: 10.1016/s0960-894x(03)00159-8.

Abstract

The SAR of a series of beta-carboline derived type 5 phosphodiesterase inhibitors has been explored and we have discovered compounds with excellent levels of PDE5 potency and selectivity over PDE6. However, the series exhibits low levels of selectivity over PDE11, a phosphodiesterase with unknown function.

MeSH terms

  • 3',5'-Cyclic-GMP Phosphodiesterases
  • Animals
  • Benzene Derivatives / chemistry
  • Benzene Derivatives / pharmacology
  • Carbolines / chemical synthesis*
  • Carbolines / chemistry
  • Carbolines / pharmacology*
  • Cattle
  • Cyclic Nucleotide Phosphodiesterases, Type 5
  • Dogs
  • Drug Design
  • Humans
  • Inhibitory Concentration 50
  • Isoenzymes
  • Phosphodiesterase Inhibitors / chemical synthesis*
  • Phosphodiesterase Inhibitors / chemistry
  • Phosphodiesterase Inhibitors / pharmacology*
  • Phosphoric Diester Hydrolases / metabolism*
  • Pyrrolidines / chemistry
  • Pyrrolidines / pharmacology
  • Recombinant Proteins / antagonists & inhibitors
  • Spodoptera
  • Structure-Activity Relationship

Substances

  • Benzene Derivatives
  • Carbolines
  • Isoenzymes
  • Phosphodiesterase Inhibitors
  • Pyrrolidines
  • Recombinant Proteins
  • Phosphoric Diester Hydrolases
  • 3',5'-Cyclic-GMP Phosphodiesterases
  • Cyclic Nucleotide Phosphodiesterases, Type 5
  • PDE5A protein, human