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

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 23.5-52.0nM) and no affinity for the 5-HT1A receptor.
(Copyright © 2016 Elsevier Ltd. All rights reserved.)