1-(1-phenethylpiperidin-4-yl)-1-phenylethanois as potent and highly selective 5-HT2A antagonists
1-(1-phenethylpiperidin-4-yl)-1-phenylethanois as potent and highly selective 5-HT2A antagonists
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DOI：
10.1002/cmdc.200500023
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发表时间：
2006-02-01
期刊：
影响因子：
3.4
通讯作者：
van Amsterdam, Christoph
中科院分区：
文献类型：
--
作者：
Heinrich, Timo;Boettcher, Henning;van Amsterdam, Christoph
本文报道了一类新型高效且选择性的 5-HT2A 拮抗剂的发现。对血清素 5-HT2A 受体的选择性进行了优化，降低了这些拮抗剂对肾上腺素能 α(1) 和多巴胺能 D-2 受体，特别是对 5-HT2C 受体的亲和力。一系列相应的 7-取代吲哚首次被描述为血清素配体。对映体 R-(+)-1-(4-氟苯基1)-1-{1-[2-(4-氟苯基)乙基]哌啶-4-基}乙醇 (R-(+)-74) 经鉴定对血清素能 5-HT2A 受体具有优异的亲和力 [IC50=0.37 nm]，并对多巴胺能 D-2- [IC50=2300 nm] 具有优异的选择性，肾上腺素能 α(1)- [IC50 = 1000 nm] 和 5-HT2C 受体 [IC50 = 490 nm]。
The discovery of a novel class of highly potent and selective 5-HT2A antagonists is reported herein. Selectivity for the serotonin 5-HT2A receptor was optimized, decreasing the affinity of these antagonists toward the adrenergic alpha(1) and dopaminergic D-2 receptors, and especially to the 5-HT2C receptor. A series of corresponding 7-substituted indoles is described for the first time as serotonergic ligands. The enantiomer R-(+)-1-(4-fluoropheny1)-1-{1-[2-(4-fluorophenyl)ethyl]piperidin-4-yl} ethanol (R-(+)-74) was identified to have superior affinity for the serotonergic 5-HT2A receptor [IC50=0.37nm] and selectivity toward the dopaminergic D-2- [IC50=2300 nm], adrenergic alpha(1)- [IC50 = 1000 nm] and 5-HT2C receptors [IC50 = 490 nm].