Synthesis and pharmacological evaluation of aryl aminosulfonamide derivatives as potent 5-HT(6) receptor antagonists

Bioorg Med Chem Lett. 2010 Aug 1;20(15):4440-3. doi: 10.1016/j.bmcl.2010.06.060. Epub 2010 Jun 12.

Abstract

A series of novel aryl aminosulfonamides was designed and synthesized as 5-HT(6) receptor ligands. Many compounds screened in a functional reporter gene based assay displayed potent antagonistic activity with Kb values in the range of 0.02-10nM. The lead compound 11m exemplified in this series showed good ADME surrogate properties, acceptable pharmacokinetic profile and is active in animal models of cognition like novel object recognition test and Morris water maze. The compound was selected for detailed profiling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cognition / drug effects
  • Cytochrome P-450 Enzyme System / metabolism
  • Drug Design
  • Humans
  • 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

  • Receptors, Serotonin
  • Serotonin Antagonists
  • Sulfonamides
  • serotonin 6 receptor
  • Cytochrome P-450 Enzyme System