Benzyl vinylogous amide substituted aryldihydropyridazinones and aryldimethylpyrazolones as potent and selective PDE3B inhibitors

Bioorg Med Chem Lett. 2003 Nov 17;13(22):3983-7. doi: 10.1016/j.bmcl.2003.08.056.

Abstract

Aryldihydropyridazinones and aryldimethylpyrazolones with 2-benzyl vinylogous amide substituents have been identified as potent PDE3B subtype selective inhibitors. Dihydropyridazinone 8a (PDE3B IC(50)=0.19 nM, 3A IC(50)=1.3 nM) was selected for in vivo evaluation of lipolysis induction, metabolic rate increase, and cardiovascular effects.

MeSH terms

  • 3',5'-Cyclic-AMP Phosphodiesterases / antagonists & inhibitors*
  • Cyclic Nucleotide Phosphodiesterases, Type 3
  • Drug Design
  • Kinetics
  • Phosphodiesterase Inhibitors / chemical synthesis*
  • Phosphodiesterase Inhibitors / pharmacology*
  • Pyridazines / chemical synthesis*
  • Pyridazines / pharmacology
  • Structure-Activity Relationship
  • Vinyl Compounds / chemical synthesis
  • Vinyl Compounds / pharmacology

Substances

  • Phosphodiesterase Inhibitors
  • Pyridazines
  • Vinyl Compounds
  • pyridazine
  • 3',5'-Cyclic-AMP Phosphodiesterases
  • Cyclic Nucleotide Phosphodiesterases, Type 3