Structure-Activity Studies of 7-Heteroaryl-3-azabicyclo[3.3.1]non-6-enes: A Novel Class of Highly Potent Nicotinic Receptor Ligands
Structure-Activity Studies of 7-Heteroaryl-3-azabicyclo[3.3.1]non-6-enes: A Novel Class of Highly Potent Nicotinic Receptor Ligands
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DOI：
10.1021/jm3011299
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发表时间：
2012-11-22
影响因子：
7.3
通讯作者：
Yohannes, Daniel
中科院分区：
文献类型：
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作者：
Breining, Scott R.;Melvin, Matt;Yohannes, Daniel
对α 4 β 2或α 7亚型具有亲和力的烟碱配体治疗诸如烟碱成瘾、神经性疼痛和神经变性和认知障碍的多种疾病的潜力已在临床上对于几种化合物显示出来，而在相关的体内模型中的临床前活性已被证明用于更多的化合物。对于几个治疗方案，我们寻求在两种亚型中具有各种亲和力和功能组合的烟碱配体，重点是双重α 4 β 2-α 7配体，以探索协同效应的可能性。我们在这里报告的结构-活性关系（SAR）的一个新的系列7-杂芳基-3-氮杂双环[3.3.1]壬-6-烯和表征许多类似物的活性在多个烟碱亚型。
The potential for nicotinic ligands with affinity for the alpha 4 beta 2 or alpha 7 subtypes to treat such diverse diseases as nicotine addiction, neuropathic pain, and neurodegenerative and cognitive disorders has been exhibited clinically for several compounds while preclinical activity in relevant in vivo models has been demonstrated for many more. For several therapeutic programs, we sought nicotinic ligands with various combinations of affinity and function across both subtypes, with an emphasis on dual alpha 4 beta 2-alpha 7 ligands, to explore, the possibility of synergistic effects. We report here the structure-activity relationships (SAR) for a novel series of 7-heteroaryl-3-azabicyclo[3.3.1]non-6-enes and characterize many of the analogues for activity at multiple nicotinic subtypes.