Synthesis, Nicotinic Acetylcholine Receptor Binding, and Antinociceptive Properties of 2′-Fluoro-3′-(substituted pyridinyl)-7-deschloroepibatidine Analogues

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• 作者：Pauline W. Ondachi ; Ana H. Castro ; Jakub M. Bartkowiak ; Charles W. Luetje ; M. Imad Damaj ; S. Wayne Mascarella ; Hernán A. Navarro ; F. Ivy Carroll
• 刊名：Journal of Medicinal Chemistry
• 出版年：2014
• 出版时间：February 13, 2014
• 年：2014
• 卷：57
• 期：3
• 页码：836-848
• 全文大小：375K
• ISSN：1520-4804

文摘

2鈥?Fluoro-3-(substituted pyridine)epibatidine analogues 7a鈥?b>e and 8a鈥?b>e were synthesized, and their in vitro and in vivo nAChR properties were determined. 2鈥?Fluoro-3鈥?(4鈥?pyridinyl)deschloroepibatidine (7a) and 2鈥?fluoro-3鈥?(3鈥?pyridinyl)deschloroepibatidine (8a) were synthesized as bioisosteres of the 4鈥?nitrophenyl lead compounds 5a and 5g. Comparison of the in vitro nAChR properties of 7a and 8a to those of 5a and 5g showed that 7a and 8a had in vitro nAChR properties similar to those of 5a and 5g but both were more selective for the 伪4尾2-nAChR relative to the 伪3尾4- and 伪7-nAChRs than 5a and 5g. The in vivo nAChR properties in mice of 7a were similar to those of 5a. In contrast, 8a was an agonist in all four mouse acute tests, whereas 5g was active only in a spontaneous activity test. In addition, 5g was a nicotine antagonist in both the tail-flick and hot-plate tests, whereas 8a was an antagonist only in the tail-flick test.