Structure鈥揂ctivity Relationship Studies of Sulfonylpiperazine Analogues as Novel Negative Allosteric Modulators of Human Neuronal Nicotinic Receptors

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• 作者：Brandon J. Henderson ; Daniel J. Carper ; Tatiana F. Gonz谩lez-Cestari ; Bitna Yi ; Kiran Mahasenan ; Ryan E. Pavlovicz ; Martin L. Dalefield ; Robert S. Coleman ; Chenglong Li ; Dennis B. McKay
• 刊名：Journal of Medicinal Chemistry
• 出版年：2011
• 出版时间：December 22, 2011
• 年：2011
• 卷：54
• 期：24
• 页码：8681-8692
• 全文大小：666K
• 年卷期：v.54,no.24(December 22, 2011)
• ISSN：1520-4804

文摘

Neuronal nicotinic receptors have been implicated in several diseases and disorders such as autism, Alzheimer鈥檚 disease, Parkinson鈥檚 disease, epilepsy, and various forms of addiction. To understand the role of nicotinic receptors in these conditions, it would be beneficial to have selective molecules that target specific nicotinic receptors in vitro and in vivo. Our laboratory has previously identified novel negative allosteric modulators of human 伪4尾2 (H伪4尾2) and human 伪3尾4 (H伪3尾4) nicotinic receptors. The effects of novel sulfonylpiperazine analogues that act as negative allosteric modulators on both H伪4尾2 nAChRs and H伪3尾4 nAChRs were investigated. This work, through structure鈥揳ctivity relationship (SAR) studies, describes the chemical features of these molecules that are important for both potency and selectivity on H伪4尾2 nAChRs.