Synthesis and biological activities of 1-pyridylisoquinoline and 1-pyridyldihydroisoquinoline derivatives as PDE4 inhibitors

Bioorg Med Chem Lett. 2003 Jul 21;13(14):2347-50. doi: 10.1016/s0960-894x(03)00438-4.

Abstract

A novel series of 1-pyridylisoquinoline and 1-pyridyldihydroisoquinoline derivatives has been prepared. These compounds showed potent PDE4 inhibitory activities and a broad margin between the K(i) value of the rolipram binding affinity and the IC(50) value of PDE4 inhibition. They also exhibited potent inhibitory activities toward LPS-induced TNF-alpha production in mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3',5'-Cyclic-AMP Phosphodiesterases / antagonists & inhibitors*
  • Animals
  • Binding, Competitive / drug effects
  • Cyclic Nucleotide Phosphodiesterases, Type 4
  • Dose-Response Relationship, Drug
  • Indicators and Reagents
  • Isoquinolines / chemical synthesis
  • Kinetics
  • Lipopolysaccharides / antagonists & inhibitors
  • Lipopolysaccharides / pharmacology
  • Mice
  • Phosphodiesterase Inhibitors / chemical synthesis*
  • Phosphodiesterase Inhibitors / metabolism
  • Phosphodiesterase Inhibitors / pharmacology*
  • Quinolines / chemical synthesis
  • Rolipram / metabolism
  • Stereoisomerism
  • Tumor Necrosis Factor-alpha / biosynthesis

Substances

  • Indicators and Reagents
  • Isoquinolines
  • Lipopolysaccharides
  • Phosphodiesterase Inhibitors
  • Quinolines
  • Tumor Necrosis Factor-alpha
  • 3',5'-Cyclic-AMP Phosphodiesterases
  • Cyclic Nucleotide Phosphodiesterases, Type 4
  • Rolipram