Do GluN2B subunit containing NMDA receptors tolerate a fluorine atom in the phenylalkyl side chain?
Do GluN2B subunit containing NMDA receptors tolerate a fluorine atom in the phenylalkyl side chain?
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含有 NMDA 受体的 GluN2B 亚基能否耐受苯烷基侧链中的氟原子？
DOI：
10.1039/c6md00621c
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发表时间：
2017
期刊：
影响因子：
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通讯作者：
Masato Kitamura and Bernhard Wuensch
中科院分区：
文献类型：
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作者：
Yoshihiro Shuto;Simone Thum; Louisa Temme; Dirk Schepmann; Masato Kitamura and Bernhard Wuensch
研究了苯并[7]轮烯-7-胺侧链上的F原子对含NMDA受体的GluN2B亚基的亲和力和对相关受体选择性的影响。5a和5b的合成是通过酮6与伯烷基胺14a和14b的还原胺化反应进行的，伯烷胺14a和14b在β位置上含有一个F原子。非氟化和氟化配体4和5的GluN2B亲和力几乎相同。F原子对GluN2B亲和力的低影响是意想不到的，因为它影响了配体的几个化学和物理化学性质。然而，F原子的引入降低了对σ受体的选择性。虽然5a和5b仍然表现出对GluN2B的偏好是σ1受体的2-3倍，但它们对GluN2B和σ2受体的亲和力几乎相同。
The influence of an F-atom in the side chain of benzo[7]annulen-7-amines on the affinity towards GluN2B subunit containing NMDA receptors and the selectivity over related receptors was investigated. The synthesis of 5a and 5b was performed by reductive amination of the ketone 6 with primary alkanamines 14a and 14b bearing an F-atom in β-position. The GluN2B affinities of non-fluorinated and fluorinated ligands 4 and 5 are almost identical. The low impact of the F-atom on GluN2B affinity was unexpected, as it influences several chemical and physicochemical properties of the ligands. However, introduction of the F-atom led to reduced selectivity over σ receptors. Whereas 5a and 5b display still a 2–3-fold preference for GluN2B over σ1 receptors, they show almost the same affinity to GluN2B and σ2 receptors.