Phenyl benzenesulfonamides are novel and selective 5-HT6 antagonists: identification of N-(2,5-dibromo-3-fluorophenyl)-4-methoxy-3-piperazin-1-ylbenzenesulfonamide (SB-357134)

Bioorg Med Chem Lett. 2001 Jan 8;11(1):55-8. doi: 10.1016/s0960-894x(00)00597-7.

Abstract

Substituted N-phenyl-4-methoxy-3-piperazin-1-ylbenzenesulfonamides and conformationally restricted analogues have been identified as high affinity and selective 5-HT6 antagonists. Compounds from this series had a range of pharmacokinetic profiles in rat and in general there was a correlation between clearance and CNS penetration. Based on its overall biological profile 2 (SB-357134) was selected for further pre-clinical evaluation.

MeSH terms

  • Animals
  • Biological Availability
  • Blood-Brain Barrier / physiology
  • Humans
  • Models, Molecular
  • Molecular Conformation
  • Molecular Structure
  • Piperazines / chemistry
  • Piperazines / pharmacokinetics
  • Piperazines / pharmacology*
  • Rats
  • Receptors, Serotonin / metabolism*
  • Serotonin Antagonists / chemical synthesis
  • Serotonin Antagonists / chemistry
  • Serotonin Antagonists / pharmacokinetics
  • Serotonin Antagonists / pharmacology*
  • Structure-Activity Relationship
  • Substrate Specificity
  • Sulfonamides / chemical synthesis
  • Sulfonamides / chemistry*
  • Sulfonamides / pharmacokinetics
  • Sulfonamides / pharmacology*

Substances

  • N-(2,5-dibromo-3-fluorophenyl)-4-methoxy-3-piperazin-1-ylbenzenesulfonamide
  • Piperazines
  • Receptors, Serotonin
  • Serotonin Antagonists
  • Sulfonamides
  • serotonin 6 receptor