Design and synthesis of new homo and hetero bis-piperazinyl-1-propanone derivatives as 5-HT7R selective ligands over 5-HT1AR. Issue 16 (15th August 2016)

• Record Type: Journal Article
• Authors: Intagliata, Sebastiano; Modica, Maria N.; Pittalà, Valeria; Salerno, Loredana; Siracusa, Maria A.; Cagnotto, Alfredo; Salmona, Mario; Romeo, Giuseppe
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 26:Issue 16(2016)
• Page Start: 4052
• Page End: 4056
• Publication Date: 2016-08-15
• Subjects: Serotonin receptors -- 5-HT7 selective ligands -- Homo bis-piperazine -- Hetero bis-piperazine -- Bivalent ligand approach; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2016.06.080
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: 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 derivatives15, 24, 25, and27 –29 displayed nanomolar affinity values for the 5-HT7 receptor ( K i 23.5–52.0 nM) and no affinity for the 5-HT1A receptor.