Synthesis and receptor binding of new thieno[2,3-d]-pyrimidines as selective ligands of 5-HT3 receptors

Maria N. Modica, Giuseppe Romeo, Loredana Salerno, Valeria Pittalà, Maria A. Siracusa, Ilario Mereghetti, Alfredo Cagnotto, Tiziana Mennini, Róbert Gáspár, Adrienn Gál, George Falkay, Márta Palkó, Gábor Maksay, Ferenc Fülüp

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5 Citations (Scopus)

Abstract

With the aim to develop new potent and selective ligands of 5-HT 3-type serotonin receptors and to acquire more information on their structure-affinity relationships, new thieno[2,3-d]pyrimidine derivatives 32-39 were synthesized and their binding to 5-HT3 versus 5-HT4 receptors was studied. Some of these new compounds exhibit good affinity for cortical 5-HT3 receptors, but not for 5-HT4 receptors. Among these derivatives, 6-ethyl-4-(4-methyl-1-piperazinyl)-2-(methylthio)- thieno[2,3-d]pyrimidine 32 is the most potent ligand (Ki = 67 nM); it behaves as a competitive antagonist of the 5-HT3 receptor function in the guinea pig colon. Its binding interactions with 5-HT3A receptors were analysed by using receptor modelling and comparative docking.

Original languageEnglish
Pages (from-to)333-343
Number of pages11
JournalArchiv der Pharmazie
Volume341
Issue number6
DOIs
Publication statusPublished - Jun 2008

Keywords

  • 5-HT receptors
  • Antagonists
  • Receptor docking
  • Thieno[2,3-d]pyrimidines /

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Drug Discovery

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    Modica, M. N., Romeo, G., Salerno, L., Pittalà, V., Siracusa, M. A., Mereghetti, I., Cagnotto, A., Mennini, T., Gáspár, R., Gál, A., Falkay, G., Palkó, M., Maksay, G., & Fülüp, F. (2008). Synthesis and receptor binding of new thieno[2,3-d]-pyrimidines as selective ligands of 5-HT3 receptors. Archiv der Pharmazie, 341(6), 333-343. https://doi.org/10.1002/ardp.200700205