A convenient synthesis by microwave heating and pharmacological evaluation of novel benzoyltriazole and saccharine derivatives as 5-HT(1A) receptor ligands

Eur J Pharm Sci. 2002 Jul;16(1-2):15-28. doi: 10.1016/s0928-0987(02)00045-3.

Abstract

A series of novel 1,2,3-4-benzoyltriazole and saccharine derivatives were designed and synthesized by microwave heating. They were evaluated on a battery of receptors, including serotonin 5-HT(1A,) 5-HT(2A) and 5-HT(2C), and the most interesting compounds were further evaluated on dopaminergic D(1), D(2) and adrenergic alpha(1), alpha(2) receptors. Conventional and microwave heating of the reactions were compared. Synthesis by microwave heating gave the desired compounds in better yields than those obtained by conventional heating. The overall times for the syntheses were considerably reduced. All compounds displayed moderate affinity for 5-HT(1A) receptor. The most interesting compound 33 showed a high affinity (K(i)=93 nM) which was combined with no affinity on the other receptors considered.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / metabolism
  • Heating
  • In Vitro Techniques
  • Ligands
  • Magnetic Resonance Spectroscopy
  • Microwaves*
  • Piperazines / chemical synthesis*
  • Piperazines / chemistry
  • Piperazines / pharmacology
  • Radioligand Assay
  • Rats
  • Rats, Wistar
  • Receptor, Serotonin, 5-HT2A
  • Receptor, Serotonin, 5-HT2C
  • Receptors, Serotonin / metabolism*
  • Receptors, Serotonin, 5-HT1
  • Saccharin / analogs & derivatives*
  • Saccharin / chemical synthesis*
  • Saccharin / chemistry
  • Saccharin / pharmacology
  • Structure-Activity Relationship
  • Triazoles / chemical synthesis*
  • Triazoles / chemistry
  • Triazoles / pharmacology

Substances

  • Ligands
  • Piperazines
  • Receptor, Serotonin, 5-HT2A
  • Receptor, Serotonin, 5-HT2C
  • Receptors, Serotonin
  • Receptors, Serotonin, 5-HT1
  • Triazoles
  • Saccharin