4-(4-Fluorobenzoyl)-1-[2-(4-iodo-2,5-dimethoxyphenyl)ethyl]piperidine and its derivatives: synthesis and affinity at 5-HT_2A, 5-HT_2B and 5-HT_2C serotonin receptors

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• 作者：Claudi ; Francesco ; Scoccia ; Loredana ; Giorgioni ; Gianfabio ; Accorroni ; Beatrice ; Marucci ; Gabriella ; et. al.
• 关键词：4-(4-Fluorobenzoyl)-1-[2-(4-iodo-2 ; 5-dimethoxyphenyl)ethyl]piperidine derivatives ; synthesis ; 5-HT_2A ; 5-HT_2B ; and 5-HT_2C serotonin receptor affinity ; 5-HT_2A antagonistic activity
• 刊名：European Journal of Medicinal Chemistry
• 出版年：1999
• 出版时间：October, 1999
• 年：1999
• 卷：34
• 期：10
• 页码：843-852
• 全文大小：129 K

文摘

4-(4-Fluorobenzoyl)-1-[2-(4-iodo-2,5-dimethoxyphenyl)ethyl]piperidine (7) and its derivatives modified at the carbonyl group of the fluorobenzoyl moiety were prepared and evaluated for affinity at 5-HT_2A, 5-HT_2C (rat cortex) and 5-HT_2B (rat stomach fundus) serotonin receptors. Compound 7 bound the 5-HT_2A sites with higher affinity (K_i = 8.2 nM) than the 5-HT_2B (K_b = 1 290 nM) and 5-HT_2C ones (K_i = 54.2 nM). Modification of the benzoyl carbonyl group decreased the 5-HT_2A and 5-HT_2C affinities but did not significantly influence 5-HT_2B affinity. This suggests that the carbonyl group is the determinant for the interaction with 5-HT_2A and 5-HT_2C receptor subtypes. Compound 7 was found to be a 5-HT_2A receptor antagonist.