Phthalazine PDE4 inhibitors. Part 3: the synthesis and in vitro evaluation of derivatives with a hydrogen bond acceptor

Bioorg Med Chem Lett. 2002 Jan 7;12(1):5-8. doi: 10.1016/s0960-894x(01)00668-0.

Abstract

This communication describes the synthesis and in vitro evaluation of a novel and potent series of phthalazine phosphodiesterase type (IV) (PDE4) inhibitors. The interaction with two distinct polar binding sites allowed us to eliminate the cyclopentyloxy substitution from rolipram-like analogues.

MeSH terms

  • 3',5'-Cyclic-AMP Phosphodiesterases / antagonists & inhibitors*
  • Binding Sites
  • Cyclic Nucleotide Phosphodiesterases, Type 4
  • Drug Design
  • Drug Evaluation, Preclinical
  • Humans
  • Hydrogen Bonding
  • Neutrophils / enzymology
  • Phosphodiesterase Inhibitors / chemical synthesis*
  • Phosphodiesterase Inhibitors / chemistry
  • Phosphodiesterase Inhibitors / pharmacology
  • Phthalazines / chemical synthesis*
  • Phthalazines / chemistry
  • Phthalazines / pharmacology
  • Rolipram / analogs & derivatives
  • Structure-Activity Relationship

Substances

  • Phosphodiesterase Inhibitors
  • Phthalazines
  • 3',5'-Cyclic-AMP Phosphodiesterases
  • Cyclic Nucleotide Phosphodiesterases, Type 4
  • Rolipram