Design and synthesis of new homo and hetero bis-piperazinyl-1-propanone derivatives as 5-HT₇R selective ligands over 5-HT_1AR

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• 作者：Sebastiano Intagliata^a ; ^{s.intagliata@studium.unict.it" class="auth_mail" title="E-mail the corresponding author} ; Maria N. Modica^a ; Valeria Pittalà ; ^a ; Loredana Salerno^a ; Maria A. Siracusa^a ; Alfredo Cagnotto^b ; Mario Salmona^b ; Giuseppe Romeo^a
• 关键词：Serotonin receptors ; 5-HT7 selective ligands ; Homo bis-piperazine ; Hetero bis-piperazine ; Bivalent ligand approach
• 刊名：Bioorganic & Medicinal Chemistry Letters
• 出版年：2016
• 出版时间：15 August 2016
• 年：2016
• 卷：26
• 期：16
• 页码：4052-4056
• 全文大小：589 K

文摘

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-HT_1A 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-HT_1A 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 (K_i 23.5–52.0 nM) and no affinity for the 5-HT_1A receptor.