Spiroquinazolinones as novel, potent, and selective PDE7 inhibitors. Part 2: Optimization of 5,8-disubstituted derivatives

Bioorg Med Chem Lett. 2004 Sep 20;14(18):4627-31. doi: 10.1016/j.bmcl.2004.07.010.

Abstract

The optimization of 5,8-disubstituted spirocyclohexane-quinazolinones into potent, selective, soluble PDE7 inhibitors with acceptable in vivo pharmacokinetic parameters is presented.

Publication types

  • Comparative Study

MeSH terms

  • 3',5'-Cyclic-AMP Phosphodiesterases / antagonists & inhibitors*
  • 3',5'-Cyclic-AMP Phosphodiesterases / classification
  • 3',5'-Cyclic-AMP Phosphodiesterases / metabolism
  • Animals
  • Biological Availability
  • Cell Line
  • Cyclic Nucleotide Phosphodiesterases, Type 7
  • Half-Life
  • Humans
  • In Vitro Techniques
  • Isoenzymes / antagonists & inhibitors*
  • Isoenzymes / classification
  • Isoenzymes / metabolism
  • Microsomes / drug effects
  • Microsomes / metabolism
  • Phosphodiesterase Inhibitors / chemistry*
  • Phosphodiesterase Inhibitors / pharmacokinetics*
  • Quinazolines / chemical synthesis*
  • Quinazolines / chemistry
  • Quinazolines / pharmacology
  • Rats
  • Spiro Compounds / chemical synthesis*
  • Spiro Compounds / chemistry
  • Spiro Compounds / pharmacology
  • Structure-Activity Relationship

Substances

  • Isoenzymes
  • Phosphodiesterase Inhibitors
  • Quinazolines
  • Spiro Compounds
  • 3',5'-Cyclic-AMP Phosphodiesterases
  • Cyclic Nucleotide Phosphodiesterases, Type 7