Bodnar Alice L, Cortes-Burgos Luz A, Cook Karen K, Dinh Dac M, Groppi Vincent E, Hajos Mihaly, Higdon Nicole R, Hoffmann William E, Hurst Raymond S, Myers Jason K, Rogers Bruce N, Wall Theron M, Wolfe Mark L, Wong Erik
Department of Neuroscience, Global Research and Development, Pfizer Inc., Groton, CT, USA.
J Med Chem. 2005 Feb 24;48(4):905-8. doi: 10.1021/jm049363q.
A library of benzamides was tested for alpha7 nicotinic acetylcholine receptor (nAChR) agonist activity using a chimeric receptor in a functional, cell-based, high-throughput assay. From this library, quinuclidine benzamides were found to have alpha7 nAChR agonist activity. The SAR diverged from the activity of this compound class verses the 5-HT(3) receptor, a structural homologue of the alpha7 nAChR. PNU-282987, the most potent compound from this series, was also shown to open native alpha7 nAChRs in cultured rat neurons and to reverse an amphetamine-induced gating deficit in rats.
在一项基于细胞的功能性高通量检测中，使用嵌合受体对一系列苯甲酰胺进行了α7烟碱型乙酰胆碱受体（nAChR）激动剂活性测试。从该系列化合物中发现，奎宁环苯甲酰胺具有α7 nAChR激动剂活性。该系列化合物的构效关系与5-HT(3)受体（α7 nAChR的结构同源物）的活性不同。该系列中最有效的化合物PNU-282987还被证明可打开培养大鼠神经元中的天然α7 nAChRs，并逆转大鼠中由苯丙胺引起的门控缺陷。
