Structure鈥揂ctivity 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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- 作者：Scott R. Breining ; Matt Melvin ; Balwinder S. Bhatti ; Gary D. Byrd ; Melanie N. Kiser ; Christopher D. Hepler ; Dawn N. Hooker ; Jenny Zhang ; Leslie A. Reynolds ; Lisa R. Benson ; Nikolai B. Fedorov ; Serguei S. Sidach ; J. Pike Mitchener ; Linda M. Lucero ; Ronald J. Lukas ; Paul Whiteaker ; Daniel Yohannes
- 刊名：Journal of Medicinal Chemistry
- 出版年：2012
- 出版时间：November 26, 2012
- 年：2012
- 卷：55
- 期：22
- 页码：9929-9945
- 全文大小：453K
- 年卷期：v.55,no.22(November 26, 2012)
- ISSN：1520-4804
文摘
The potential for nicotinic ligands with affinity for the 伪4尾2 or 伪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 伪4尾2鈭捨? ligands, to explore the possibility of synergistic effects. We report here the structure鈥揳ctivity 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.