Identification of novel indanylsulfonamide guanylhydrazones as potent 5-HT6 serotonin receptor antagonists

J Med Chem. 2009 Oct 8;52(19):6153-7. doi: 10.1021/jm900796p.

Abstract

Changing the N,N-(dimethylamino)ethyl side chain in the N-[3-(aminoethyl)inden-5-yl]sulfonamide 5-HT(6) serotonin receptor agonists 1 by a conformationally rigid guanylhydrazone moiety at the indene 3-position led to the identification of the title indanylguanylhydrazones 6, which exhibited excellent binding affinities and an antagonistic response at the 5-HT(6) receptor, with K(i) and IC(50) values in the nanomolar range (K(i) >or= 1.2 nM, IC(50) >or= 47 nM, and I(max) <or= 173%).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Guanosine Monophosphate / chemistry
  • Guanosine Monophosphate / pharmacology
  • Humans
  • Hydrazones / chemical synthesis
  • Hydrazones / pharmacology*
  • Indenes
  • Inhibitory Concentration 50
  • Protein Binding
  • Receptors, Serotonin / drug effects*
  • Serotonin Antagonists / chemical synthesis*
  • Structure-Activity Relationship
  • Sulfonamides / chemistry
  • Sulfonamides / pharmacology

Substances

  • Hydrazones
  • Indenes
  • Receptors, Serotonin
  • Serotonin Antagonists
  • Sulfonamides
  • serotonin 6 receptor
  • Guanosine Monophosphate