Pyrazoloquinolines as PDE10A inhibitors: discovery of a tool compound

Bioorg Med Chem Lett. 2012 Feb 1;22(3):1335-9. doi: 10.1016/j.bmcl.2011.12.080. Epub 2011 Dec 21.

Abstract

A series of pyrazoloquinolines, possessing (hetero)arylhydroxymethyl substituents at the quinoline C-4 position were evaluated as PDE10A inhibitors. Among these, methylpyrimidyl analogue 15 was identified as having good rodent and monkey exposure, and a MED of 10 mg/kg in an in vivo model.

MeSH terms

  • Animals
  • Drug Discovery*
  • Enzyme Activation / drug effects
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacokinetics
  • Enzyme Inhibitors / pharmacology*
  • Haplorhini
  • Hepatocytes / drug effects
  • Hepatocytes / metabolism
  • Inhibitory Concentration 50
  • Molecular Structure
  • Phosphoric Diester Hydrolases / metabolism*
  • Pyrazolones / chemical synthesis
  • Pyrazolones / chemistry
  • Pyrazolones / pharmacokinetics
  • Pyrazolones / pharmacology
  • Quinolines / chemical synthesis
  • Quinolines / chemistry*
  • Quinolines / pharmacokinetics
  • Quinolines / pharmacology*
  • Rats

Substances

  • Enzyme Inhibitors
  • Pyrazolones
  • Quinolines
  • PDE10A protein, human
  • Phosphoric Diester Hydrolases