Phthalazine PDE4 inhibitors. Part 2: the synthesis and biological evaluation of 6-methoxy-1,4-disubstituted derivatives

Bioorg Med Chem Lett. 2001 Jan 8;11(1):33-7. doi: 10.1016/s0960-894x(00)00587-4.

Abstract

This communication describes the synthesis and in vitro evaluation of a novel and potent series of phosphodiesterase type IV (PDE4) inhibitors. The compounds described present substituents in position 4 of the phthalazine ring to replace the commonly observed cyclopentyloxy moiety of rolipram analogues. Preliminary evidences of reduced side effects compared to standards and improved pharmacokinetic properties for selected derivatives are also reported.

MeSH terms

  • 3',5'-Cyclic-AMP Phosphodiesterases / antagonists & inhibitors*
  • 3',5'-Cyclic-AMP Phosphodiesterases / metabolism
  • Animals
  • Benzamides / pharmacology
  • Biological Availability
  • Cyclic Nucleotide Phosphodiesterases, Type 4
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Guinea Pigs
  • Humans
  • Inhibitory Concentration 50
  • Molecular Structure
  • Monocytes / drug effects
  • Monocytes / metabolism
  • Neutrophils / drug effects
  • Neutrophils / enzymology
  • Phthalazines / chemical synthesis*
  • Phthalazines / chemistry
  • Phthalazines / pharmacology*
  • Protein Binding
  • Pyridines / pharmacology
  • Rolipram / metabolism
  • Tumor Necrosis Factor-alpha / biosynthesis

Substances

  • Benzamides
  • Enzyme Inhibitors
  • Phthalazines
  • Pyridines
  • Tumor Necrosis Factor-alpha
  • 3',5'-Cyclic-AMP Phosphodiesterases
  • Cyclic Nucleotide Phosphodiesterases, Type 4
  • Rolipram
  • piclamilast