Synthesis and Structure-Activity Relationships of 3,8-Diazabicyclo[4.2.0]octane Ligands, Potent Nicotinic Acetylcholine Receptor Agonists
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- 作者：Jennifer M. Frost (né ; e Pace) ; William H. Bunnelle ; Karin R. Tietje ; David J. Anderson ; Lynne E. Rueter ; Peter Curzon ; Carol S. Surowy ; Jianquo Ji ; Jerome F. Daanen ; Kathy L. Kohlhaas ; Michael J
- 刊名：Journal of Medicinal Chemistry
- 出版年：2006
- 出版时间：December 28, 2006
- 年：2006
- 卷：49
- 期：26
- 页码：7843 - 7853
- 全文大小：236K
- 年卷期：v.49,no.26(December 28, 2006)
- ISSN：1520-4804
文摘
A series of potent neuronal nicotinic acetylcholine receptor (nAChR) ligands based on a 3,8-diazabicyclo[4.2.0]octane core have been synthesized and evaluated for affinity and agonist efficacy at the human highaffinity nicotine recognition site (h
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2) and in a rat model of persistent nociceptive pain (formalin model).Numerous analogs in this series exhibit picomolar affinity in radioligand binding assays and nanomolaragonist potency in functional assays, placing them among the most potent nAChR ligands known for theh42 receptor. Several of the compounds reported in this study (i.e., 24, 25, 28, 30, 32, and 47) exhibitequivalent or greater affinity for the h42 receptor relative to epibatidine, and like epibatidine, manyexhibit robust analgesic efficacy in the rat formalin model of persistent pain.
42) and in a rat model of persistent nociceptive pain (formalin model).Numerous analogs in this series exhibit picomolar affinity in radioligand binding assays and nanomolaragonist potency in functional assays, placing them among the most potent nAChR ligands known for theh42 receptor. Several of the compounds reported in this study (i.e., 24, 25, 28, 30, 32, and 47) exhibitequivalent or greater affinity for the h42 receptor relative to epibatidine, and like epibatidine, manyexhibit robust analgesic efficacy in the rat formalin model of persistent pain.