Novel nicotinic receptor ligands
1994; Birkhäuser; Linguagem: Inglês
10.1007/978-3-0348-7416-8_9
ISSN2504-3684
AutoresWolfgang Fiedler, Małgorzata Dukat, M. Imad Damaj, Billy R. Martin, Richard A. Glennon, Li Hong Teng, Alain Ravard, Susan T. Buxton, Peter A. Crooks, Linda P. Dwoskin, Chuan-Gui Liu, Hai Ming Wang, De-lu Zhao, Zhan-Guo Gao, Wenyu Cui, Shuping Zhang, Qing-Suo Qiao, Yun-Zhang Ran, J. Michael McIntosh, David S. Johnson, Doju Yoshikami, Eve Mahé, David B. Nielsen, Jean Rivier, W. R. Gravy, B.M. Olivera, William R. Kem, Vladimir M. Mahnir, Bo Lin, Christopher J. Lingle, Roger L. Papke, Katalin Prókai‐Tátrai,
Tópico(s)Fluorine in Organic Chemistry
ResumoFew agents (agonists) bind at [3H]nicotine-labeled nicotine receptors with an affinity comparable to that of nicotine. We initially approached this problem by undertaking a systematic structure-affinity study to determine the contribution to binding of various aspects of the nicotine molecule and of nicotine-related derivatives. For example a series of aryl-substituted and unsubstituted, primary, secondary, and tertiary amine derivatives of 3-(aminomethyl)pyridine (1) were prepared and examined. The finding that 1 (R = Me, R’ = Et, X = H) binds with good affinity (Ki = 28 nM) led to the synthesis of several conformationally-restricted analogs, such as 2 and 3 (Ki = 85 and 12 nM, respectively). With the availability of such structure-affinity and conformational data, it should now be possible to optimize affintiy by design and synthesis of new compounds. (Supported in part by funding from TDC/CIT.)
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