Pyrazolo[1,5-a]pyrimidine acetamides: 4-Phenyl alkyl ether derivatives as potent ligands for the 18 kDa translocator protein (TSPO)

Bioorg Med Chem Lett. 2010 Oct 1;20(19):5799-802. doi: 10.1016/j.bmcl.2010.07.135. Epub 2010 Aug 4.

Abstract

Herein, we report the synthesis of four new phenyl alkyl ether derivatives (7, 9-11) of the pyrazolo[1,5-a]pyrimidine acetamide class, all of which showed high binding affinity and selectivity for the TSPO and, in the case of the propyl, propargyl, and butyl ether derivatives, the ability to increase pregnenolone biosynthesis by 80-175% over baseline in rat C6 glioma cells. While these compounds fit our in silico generated pharmacophore for TSPO binding the current model does not account for the observed functional activity.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acetamides / chemical synthesis
  • Acetamides / chemistry*
  • Acetamides / pharmacology
  • Animals
  • Carrier Proteins / antagonists & inhibitors*
  • Carrier Proteins / metabolism
  • Cell Line, Tumor
  • Ethers / chemical synthesis
  • Ethers / chemistry*
  • Ethers / pharmacology
  • Ligands
  • Pregnenolone / biosynthesis
  • Protein Binding
  • Pyrazoles / chemistry*
  • Pyridines / chemistry*
  • Rats
  • Receptors, GABA-A / metabolism

Substances

  • Acetamides
  • Carrier Proteins
  • Ethers
  • Ligands
  • Pyrazoles
  • Pyridines
  • Receptors, GABA-A
  • pyrazolopyridine
  • Tspo protein, rat
  • Pregnenolone