Model studies on a synthetically facile series of N-substituted phenyl-N'-pyridin-3-yl ureas leading to 1-(3-pyridylcarbamoyl) indolines that are potent and selective 5-HT(2C/2B) receptor antagonists

Bioorg Med Chem. 1999 Dec;7(12):2767-73. doi: 10.1016/s0968-0896(99)00228-x.

Abstract

A model series of 5-HT2C antagonists have been prepared by rapid parallel synthesis. These N-substituted phenyl-N'-pyridin-3-yl ureas were found to have a range of 5-HT2C receptor affinities and selectivities over the closely related 5-HT2A receptor. Extrapolation of simple SAR, derived from this set of compounds, to the more active but synthetically more complex 1-(3-pyridylcarbamoyl)indoline series allowed us to target optimal substitution patterns and identify potent and selective 5-HT(2C/2B) antagonists.

MeSH terms

  • Animals
  • Humans
  • In Vitro Techniques
  • Kinetics
  • Magnetic Resonance Spectroscopy
  • Models, Chemical
  • Phenylurea Compounds / chemical synthesis
  • Phenylurea Compounds / chemistry*
  • Phenylurea Compounds / pharmacology*
  • Pyridines / chemical synthesis
  • Pyridines / chemistry*
  • Pyridines / pharmacology*
  • Receptor, Serotonin, 5-HT2B
  • Receptor, Serotonin, 5-HT2C
  • Receptors, Serotonin / drug effects*
  • Receptors, Serotonin / metabolism
  • Serotonin Antagonists / chemical synthesis
  • Serotonin Antagonists / chemistry*
  • Serotonin Antagonists / pharmacology*
  • Structure-Activity Relationship

Substances

  • Phenylurea Compounds
  • Pyridines
  • Receptor, Serotonin, 5-HT2B
  • Receptor, Serotonin, 5-HT2C
  • Receptors, Serotonin
  • Serotonin Antagonists