Indole-3-piperazinyl derivatives: novel chemical class of 5-HT(6) receptor antagonists

Bioorg Med Chem Lett. 2011 Jan 1;21(1):346-9. doi: 10.1016/j.bmcl.2010.11.001. Epub 2010 Nov 5.

Abstract

N(1)-Arylsulfonyl-3-piperazinyl indole derivatives were designed and identified as a novel class of 5-HT(6) receptors ligands. All the compounds have high affinity and antagonist activity towards 5-HT(6) receptor. The compound 7a (K(i) = 3.4 nM, functional assay IC(50) = 310 nM) shows enhanced cognitive effect when tested in NORT and Morris water maze models. Synthesis, SAR and PK profile of these novel compounds constitute the subject matter of this Letter.

MeSH terms

  • Administration, Oral
  • Animals
  • Humans
  • Indoles / chemical synthesis
  • Indoles / chemistry*
  • Indoles / pharmacokinetics
  • Male
  • Microsomes, Liver / metabolism
  • Piperazines / chemical synthesis
  • Piperazines / chemistry*
  • Piperazines / pharmacokinetics
  • Protein Binding
  • Rats
  • Rats, Wistar
  • Receptors, Serotonin / chemistry*
  • Receptors, Serotonin / metabolism
  • Serotonin Antagonists / chemical synthesis
  • Serotonin Antagonists / chemistry*
  • Serotonin Antagonists / pharmacokinetics
  • Structure-Activity Relationship
  • Sulfonamides / chemical synthesis
  • Sulfonamides / chemistry*
  • Sulfonamides / pharmacokinetics

Substances

  • Indoles
  • Piperazines
  • Receptors, Serotonin
  • Serotonin Antagonists
  • Sulfonamides
  • serotonin 6 receptor