Synthesis and biological evaluation of 4-nitroindole derivatives as 5-HT2A receptor antagonists

Bioorg Med Chem. 2015 Mar 15;23(6):1313-20. doi: 10.1016/j.bmc.2015.01.032. Epub 2015 Jan 24.

Abstract

A novel series of 4-nitroindole sulfonamides containing a methyleneamino-N,N-dimethylformamidine were prepared. The binding of these compounds to 5-HT2A and 5-HT2C was evaluated, and most of the compounds showed IC50 values of less than 1μM, and exhibited high selectivity for the 5-HT2C receptor. However, little selectivity was observed in the functional assay for 5-HT6 receptors. The computational modeling studies further validated the biological results and also demonstrated a reasonable correlation between the activity of compounds and the mode of superimposition with specified pharmacophoric features.

Keywords: 4-Nitroindole; 5-HT(2A); 5-HT(2C); 5-HT(6) receptor; Methyleneamino-N,N-dimethylformamidine group; Sulfonamides.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Dose-Response Relationship, Drug
  • Humans
  • Indoles / chemical synthesis
  • Indoles / chemistry
  • Indoles / pharmacology*
  • Molecular Structure
  • Nitro Compounds / chemical synthesis
  • Nitro Compounds / chemistry
  • Nitro Compounds / pharmacology*
  • Receptor, Serotonin, 5-HT2A / metabolism*
  • Recombinant Proteins / metabolism
  • Serotonin 5-HT2 Receptor Antagonists / chemical synthesis*
  • Serotonin 5-HT2 Receptor Antagonists / chemistry
  • Serotonin 5-HT2 Receptor Antagonists / pharmacology*
  • Structure-Activity Relationship

Substances

  • Indoles
  • Nitro Compounds
  • Receptor, Serotonin, 5-HT2A
  • Recombinant Proteins
  • Serotonin 5-HT2 Receptor Antagonists