Design and synthesis of new homo and hetero bis-piperazinyl-1-propanone derivatives as 5-HT7R selective ligands over 5-HT1AR

Sebastiano Intagliata, Maria N. Modica, Valeria Pittalà, Loredana Salerno, Maria A. Siracusa, Alfredo Cagnotto, Mario Salmona, Giuseppe Romeo

Research output: Contribution to journalArticle


In this work we report the discovery of new homo and hetero bis-piperazinyl-1-propanone derivatives as selective ligands for 5-HT7 over 5-HT1A receptor. These newly synthesized compounds possess a 4-arylpiperazine linked through an acyl spacer to another substituted piperazine system and were tested for their binding properties on human cloned 5-HT1A and 5-HT7 serotonin receptors. Among these, phenyl, 4- and 2-chlorophenyl, 2-methoxyphenyl, 2-pyridyl, and 2-pyrimidyl derivatives 15, 24, 25, and 27–29 displayed nanomolar affinity values for the 5-HT7 receptor (Ki 23.5–52.0 nM) and no affinity for the 5-HT1A receptor.

Original languageEnglish
Pages (from-to)4052-4056
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Issue number16
Publication statusPublished - Aug 15 2016



  • 5-HT selective ligands
  • Bivalent ligand approach
  • Hetero bis-piperazine
  • Homo bis-piperazine
  • Serotonin receptors

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Molecular Biology
  • Molecular Medicine
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science

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