Di- and trisubstituted pyrazolo[1,5-a]pyridine derivatives: synthesis, dopamine receptor binding and ligand efficacy

Bioorg Med Chem Lett. 2002 Feb 25;12(4):633-6. doi: 10.1016/s0960-894x(01)00814-9.

Abstract

Based on the lead molecule FAUC 113, a series of di- and trisubstituted pyrazolo[1,5-a]pyridine derivatives was synthesized and investigated for their dopamine receptor binding profile. The carbonitrile 11a (FAUC 327) showed excellent pharmacological properties combining high D4 affinity (K(i)=1.5 nM) and selectivity with significant intrinsic activity (31%) in low nanomolar concentrations (EC50=1.5 nM).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Dopamine Agonists / chemical synthesis*
  • Dopamine Agonists / metabolism
  • Dopamine Agonists / pharmacology
  • Humans
  • Ligands
  • Protein Binding
  • Pyrazoles / chemistry
  • Pyrazoles / metabolism
  • Pyridines / chemical synthesis*
  • Pyridines / chemistry
  • Pyridines / metabolism
  • Pyridines / pharmacology*
  • Receptors, Dopamine / metabolism*
  • Receptors, Dopamine D2 / agonists
  • Receptors, Dopamine D4
  • Structure-Activity Relationship

Substances

  • 3-(4-(4-chlorophenyl)piperazinylmethyl)pyrazolo(1,5-a)pyridine
  • DRD4 protein, human
  • Dopamine Agonists
  • Ligands
  • Pyrazoles
  • Pyridines
  • Receptors, Dopamine
  • Receptors, Dopamine D2
  • Receptors, Dopamine D4