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New Rigid Nicotine Analogues, Carrying a Norbornane Moiety, Are Potent Agonists of $\upalpha$7 and $\upalpha$3\ast Nicotinic Receptorsстатья
Статья опубликована в высокорейтинговом журнале
Информация о цитировании статьи получена из
Web of Science,
Scopus
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 11 ноября 2019 г.
- Авторы: Manetti Dina, Garifulina Alexandra, Bartolucci Gianluca, Bazzicalupi Carla, Bellucci Cristina, Chiaramonte Niccolò, Dei Silvia, Mannelli Lorenzo Di Cesare, Ghelardini Carla, Gratteri Paola, Spirova Ekaterina, Shelukhina Irina, Teodori Elisabetta, Varani Katia, Tsetlin Victor, Romanelli Maria Novella
- Журнал: Journal of Medicinal Chemistry
- Том: 62
- Номер: 4
- Год издания: 2019
- Издательство: American Chemical Society
- Местоположение издательства: United States
- Первая страница: 1887
- Последняя страница: 1901
- DOI: 10.1021/acs.jmedchem.8b01372
- Аннотация: A three-dimensional database search has been applied to design a series of endo- and exo-3-(pyridin-3-yl)bicyclo[2.2.1]heptan-2-amines as nicotinic receptor ligands. The synthesized compounds were tested in radioligand binding assay on rat cortex against [H-3]-cytisine and [3H]-methyllycaconitine to measure their affinity for alpha 4 beta 2* and alpha 7* nicotinic receptors. The new derivatives showed some preference for the alpha 4 beta 2* over the alpha 7* subtype, with their affinity being dependent on the endo/exo isomerism and on the methylation degree of the basic nitrogen. The endo primary amines displayed the lowest K-i values on both receptor subtypes. Selected compounds (1a, 2a, 3a, and 6a) were tested on heterologously expressed alpha 4 beta 2, alpha 7, and alpha 3 beta 2 receptors and on SHSY-5Y cells. Compounds 1a and 2a showed alpha 4 beta 2 antagonistic properties while behaved as full agonists on recombinant alpha 7 and on SHSYSY cells. On the alpha 3 beta 2 subtype, only the chloro derivative 2a showed full agonist activity and submicromolar potency (EC50 = 0.43 mu M). The primary amines described here represent new chemotypes for the alpha 7 and alpha 3* receptor subtypes.
- Добавил в систему: Смирнова Инна Григорьевна