Novel antagonists of 5-HT3 receptors. Synthesis and biological evaluation of piperazinylquinoxaline derivatives

  • J Med Chem. 1993 Sep 17;36(19):2745-50. doi: 10.1021/jm00071a005.
A Monge  1 ,  J A Palop ,  J C Del Castillo ,  J M Calderó ,  J Roca ,  G Romero ,  J Del Río ,  B Lasheras
Affiliations
  • 1. Department Química Orgánica y CIFA, Universidad de Navarra, Pamplona, Spain.
PMID: 8410988 DOI: 10.1021/jm00071a005
Abstract

A series of piperazinylquinoxalines has been synthesized and studied as 5-HT3 receptor antagonists in different preparations. Antagonism to 5-HT in the longitudinal muscle of the guinea pig ileum was particularly prominent in cyanoquinoxaline derivatives with an alkyl substitutuent on the piperazine moiety. The pA2 of some selected compounds against the 5-HT3 agonist 2-methyl-5HT in the guinea pig ileum was in the range of tropisetron or ondansetron, and one of them, 7e, was more potent than these reference compounds by approximately 2 or 3 orders of magnitude. However, these compounds were markedly less potent than either tropisetron or ondansetron as displacers of 3H-BRL 43694 binding to rat cortical membranes or as antagonists of the Bezold-Jarisch reflex in rats. Piperazinylcyanoquinoxalines represent a new class of 5-HT3 antagonists with a selective effect on guinea pig peripheral receptors.

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