Structural analysis and optimization of NK1 receptor antagonists through modulation of atropisomer interconversion properties
Structural analysis and optimization of NK1 receptor antagonists through modulation of atropisomer interconversion properties
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DOI：
10.1021/jm030197g
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发表时间：
2004-01-29
影响因子：
7.3
通讯作者：
Russell, K
中科院分区：
文献类型：
--
作者：
Albert, JS;Ohnmacht, C;Russell, K
我们之前描述了一系列对 NK1 受体表现出高效力和选择性的拮抗剂。然而，这些化合物也具有作为相互转化的旋转异构体的混合物存在的不期望的性质。在这里，我们证明 2-萘基取代基的改变可以调节异构体交换的速率。 NK1 受体对各种构象的亲和力的比较。形式促进了详细的 NK1 药效团模型的开发。
We have previously described a series of antagonists that showed high potency and selectivity for the NK1 receptor. However, these compounds also had the undesirable property of existing as a mixture of interconverting rotational isomers. Here we show that alteration of the 2-naphthyl substituent can modulate the rate of isomer exchange. Comparisons of the NK1 receptor affinity for the various conformational. forms has facilitated the development of a detailed NK1 pharmacophore model.