Thiazole as a carbonyl bioisostere. A novel class of highly potent and selective 5-HT3 receptor antagonists

J Med Chem. 1990 Oct;33(10):2715-20. doi: 10.1021/jm00172a006.


A novel structural class of highly potent and selective 5-HT3 receptor antagonists is described. The compounds in this new series contain a thiazole moiety linking an aromatic group and a nitrogen-containing basic region; the thiazole group appears to be acting as a carbonyl bioisostere in this system. An optimized member of this series, 4-(2-methoxyphenyl)-2-[[4(5)-methyl-5(4)-imidazolyl]methyl]thiazole (5), exhibits oral activity in the Bezold-Jarisch reflex paradigm comparable to or better than the standard agents ondansetron (1) and ICS-205-930 (2). Several of the structure-activity relationships are rationalized in terms of a computer pharmacophore model for 5-HT3 receptor binding.

MeSH terms

  • Administration, Oral
  • Animals
  • Computer Graphics
  • In Vitro Techniques
  • Mice
  • Models, Molecular
  • Neurons / metabolism
  • Radioligand Assay
  • Rats
  • Receptors, Serotonin / classification
  • Receptors, Serotonin / drug effects*
  • Serotonin Antagonists / chemical synthesis*
  • Serotonin Antagonists / metabolism
  • Serotonin Antagonists / pharmacology
  • Structure-Activity Relationship
  • Thiazoles / administration & dosage
  • Thiazoles / chemistry
  • Thiazoles / pharmacology*
  • Tumor Cells, Cultured


  • Receptors, Serotonin
  • Serotonin Antagonists
  • Thiazoles