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 journalArticle

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 compound with higher affinity and selectivity for the 5-HT3 over the 5-HT4 receptor was the 3-amino-2-(4-benzyl-l-piperazinyl)-5,6-dimethyl-thieno[2,3-d]pyrimidin-4(3H)- one 28 (5-HT3 Ki = 3.92 nM, 5-HT4 not active), the compound with higher affinity and selectivity for the 5-HT4 over the 5-HT3 receptor was the 2-[4-[4-(2-pyrimidinyl)-l-piperazinyl]butanoylamino]-4,5-dimethyl-3-thiophene carboxylic acid ethyl ester 41 (5-HT4Ki= 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)1065-1079
Number of pages15
JournalEuropean Journal of Medicinal Chemistry
Volume35
Issue number12
DOIs
Publication statusPublished - 2000

Keywords

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

ASJC Scopus subject areas

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

Fingerprint Dive into the research topics of 'Design, synthesis and binding properties of novel and selective 5-HT<sub>3</sub> and 5-HT<sub>4</sub> receptor ligands'. Together they form a unique fingerprint.

  • Cite this