Synthesis and the 5-HT6 receptor antagonistic effect of 3-arylsulfonylamino-5,6-dihydro-6-substituted pyrazolo[3,4]pyridinones for neuropathic pain treatment

Bioorg Med Chem Lett. 2013 Aug 15;23(16):4696-700. doi: 10.1016/j.bmcl.2013.05.100. Epub 2013 Jun 18.

Abstract

A novel series of 3-arylsulfonylamino-5,6-dihydro-6-substituted-1H-pyrazolo[3,4-c]pyridine-7-ones was designed and synthesized as 5-HT6 ligands. Among the derivatives synthesized, the lead compound, 12b, having piperidine functionality at the 6-position and (1-naphthyl)sulfonamino at the 3-position of the core structure showed the most potent 5-HT6 inhibitory activity in vitro, good stability without CYP liability, and good neuropathic pain alleviation activity in a rat animal model.

Keywords: 5-HT(6) receptor antagonist; Arylsufonylamino-5,6-dihydro-pyrazolo[3,4-c]pyridine-7-one; Neuropathic pain; Synthesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Drug Stability
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Inhibitory Concentration 50
  • Molecular Structure
  • Neuralgia / drug therapy
  • Protein Binding / drug effects
  • Pyrazoles / chemical synthesis
  • Pyrazoles / chemistry
  • Pyrazoles / pharmacology
  • Pyridones / chemical synthesis*
  • Pyridones / chemistry
  • Pyridones / pharmacology*
  • Rats
  • Receptors, Serotonin / metabolism*

Substances

  • Enzyme Inhibitors
  • Pyrazoles
  • Pyridones
  • Receptors, Serotonin
  • serotonin 6 receptor