N‐(4‐(4‐(2‐Halogenophenyl)piperazin‐1‐yl)butyl) Substituted Cinnamoyl Amide Derivatives as Dopamine D2 and D3 Receptor Ligands
N‐(4‐(4‐(2‐Halogenophenyl)piperazin‐1‐yl)butyl) Substituted Cinnamoyl Amide Derivatives as Dopamine D2 and D3 Receptor Ligands
复制标题
N-(4-(4-(2-卤代苯基)哌嗪-1-基)丁基)取代肉桂酰酰胺衍生物作为多巴胺 D2 和 D3 受体配体
DOI：
10.1002/ardp.200600196
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发表时间：
2007
影响因子：
5.1
通讯作者：
H. Stark
中科院分区：
文献类型：
--
作者：
O. Saur;Anneke E. Hackling;S. Perachon;J. Schwartz;P. Sokoloff;H. Stark
合成了一系列8个取代的N-（4-（4-（2-卤代苯基）哌嗪-1-基）丁基）-3-苯基丙烯酰胺衍生物，并筛选了其与多巴胺hD2和hD 3受体的结合亲和力。所有化合物均显示出高至显著的受体亲和力，并且一些化合物导致对D3受体的不同选择性。已观察到3-（4-氨基苯基）-N-（4-（4-（2-氟苯基）哌嗪-1-基）丁基）丙烯酰胺的D3受体亲和力最高（hD 3 Ki 0.9 nM; hD2 Ki 17.4 nM）。3-（4-氯苯基）-N-（4-（4-（2-氟苯基）哌嗪-1-基）丁基）丙烯酰胺的选择性比最好，对hD 3的偏好是对hD2的56倍。通过有丝分裂试验对N-（4-（4-（2-氟苯基）哌嗪-1-基）丁基）-3，3-二苯基丙烯酰胺进行了功能活性试验，令人惊讶的是，其显示出完全的激动剂性质。
A series of eight substituted N‐(4‐(4‐(2‐halogenophenyl)piperazin‐1‐yl)butyl)‐3‐phenylacryl amide derivatives have been synthesized and screened for binding affinities at dopamine hD2 and hD3 receptors. All compounds have shown high to remarkable receptor affinities and some have led to distinct selectivity for D3 receptors. Highest D3‐receptor affinity has been observed for 3‐(4‐aminophenyl)‐N‐(4‐(4‐(2‐fluorophenyl)piperazin‐1‐yl)butyl)acryl amide (hD3 Ki 0.9 nM; hD2 Ki 17.4 nM). Selectivity ratio has been best for 3‐(4‐chlorophenyl)‐N‐(4‐(4‐(2‐fluorophenyl)piperazin‐1‐yl)butyl)acryl amide with a 56‐fold preference for hD3 versus hD2. A functional activity test has been performed by a mitogenesis test for N‐(4‐(4‐(2‐fluorophenyl)piperazin‐1‐yl)butyl)‐3,3‐diphenylacryl amide, which, surprisingly, has shown full agonist properties.