Design, synthesis and binding properties of novel and selective 5-HT3 and 5-HT4 receptor ligands

Maria Modica, Maria Santagati, Salvatore Guccione, Filippo Russo, Alfredo Cagnotto, Mara Goegan, Tiziana Mennini

Research output: Contribution to journalArticlepeer-review

Abstract

This work reports the synthesis and the binding tests on the 5-HT3 and 5-HT4 receptors of new thienopyrimidopiperazine and piperazinylacylaminodimethylthiophene derivatives, in order to identify potent and selective ligands for each receptor. The 3-amino-2-(4-benzyl-1-piperazinyl)-5,6-dimethyl-thieno[2,3-d]pyrimidin-4 (3H)-one derivative 28 showed the highest affinity and selectivity for the 5-HT3 over the 5-HT4 receptor (5-HT3 Ki = 3.92 nM, 5-HT4 not active), whereas the 2-[4-[4-(2-pyrimidinyl)-1-piperazinyl]butanoylamino]-4,5-dimethyl-3- thiophenecarboxylic acid ethyl ester (41) showed the highest affinity and selectivity for the 5-HT4 over the 5-HT3 receptor (5-HT4 Ki = 81.3 nM, 5-HT3 not active). Conformational analyses were carried out on the compounds of the piperazinylacylaminodimethylthiophene series (39-42) taking compound 41 as the template.

Original languageEnglish
Pages (from-to)287-301
Number of pages15
JournalEuropean Journal of Medicinal Chemistry
Volume36
Issue number3
DOIs
Publication statusPublished - Apr 1 2001

Keywords

  • 5-HT and 5-HT receptors
  • Arylpiperazines
  • Conformational analysis
  • Ligands

ASJC Scopus subject areas

  • Molecular Medicine
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science

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