Stoit Axel R, den Hartog Arnold P, Mons Harry, van Schaik Sjoerd, Barkhuijsen Nynke, Stroomer Cees, Coolen Hein K A C, Reinders Jan Hendrik, Adolfs Tiny J P, van der Neut Martina, Keizer Hiskias, Kruse Chris G
Solvay Pharmaceuticals, Research Laboratories, C.J. van Houtenlaan 36, 1381 CP Weesp, The Netherlands.
Bioorg Med Chem Lett. 2008 Jan 1;18(1):188-93. doi: 10.1016/j.bmcl.2007.10.101. Epub 2007 Nov 1.
We have investigated a series of 7-azaindoles as potential partial agonists of the alpha4beta2 nicotinic acetylcholine receptor (nAChR). Three series of 7-azaindole derivatives have been synthesized and evaluated for rat brain neuronal nicotinic receptor affinity and functional activity. Compound (+)-51 exhibited the most potent nAChR binding (Ki = 10 nM). Compound 30A demonstrated both moderate binding affinity and partial agonist potency, thus representing a promising lead for the indications of cognition and smoking cessation.
我们研究了一系列7-氮杂吲哚作为α4β2烟碱型乙酰胆碱受体（nAChR）的潜在部分激动剂。合成了三个系列的7-氮杂吲哚衍生物，并评估了它们对大鼠脑神经元烟碱型受体的亲和力和功能活性。化合物（+）-51表现出最强的nAChR结合能力（Ki = 10 nM）。化合物30A表现出中等的结合亲和力和部分激动剂效力，因此对于认知和戒烟适应症而言是一个有前景的先导化合物。
