Pharmacophore based synthesis of 3-chloroquinoxaline-2-carboxamides as serotonin3 (5-HT3) receptor antagonist

Biol Pharm Bull. 2004 Sep;27(9):1403-5. doi: 10.1248/bpb.27.1403.

Abstract

A series of 3-chloroquinoxaline-2-carboxamides were designed and prepared by the condensation of 3-chloro-2-quinoxaloylchloride with appropriate Mannich bases of the p-aminophenol in the microwave environment. The synthesized compounds were evaluated for serotonin(3) (5-HT(3)) receptor antagonistic activities in longitudinal muscle-myenteric plexus (LMMP) preparation from guinea pig ileum against the 5-HT(3) agonist, 2-methyl-5-HT. Compound 3g exhibited comparable 5-HT(3) antagonistic activity (pA(2) 6.4) to that of standard antagonist Ondansetron (pA(2) 6.9), while the other compounds exhibited mild to moderate 5-HT(3) antagonistic activities.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Guinea Pigs
  • Ileum / drug effects
  • In Vitro Techniques
  • Male
  • Molecular Structure
  • Muscle Contraction / drug effects
  • Muscle, Smooth / drug effects
  • Myenteric Plexus
  • Quinoxalines / chemical synthesis*
  • Quinoxalines / pharmacology
  • Serotonin / analogs & derivatives*
  • Serotonin / pharmacology
  • Serotonin 5-HT3 Receptor Antagonists*
  • Serotonin Antagonists / chemical synthesis
  • Serotonin Antagonists / pharmacology
  • Structure-Activity Relationship

Substances

  • Quinoxalines
  • Serotonin 5-HT3 Receptor Antagonists
  • Serotonin Antagonists
  • Serotonin
  • 2-methyl-5-HT