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

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Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 11 ноября 2019 г.

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[1] New rigid nicotine analogues, carrying a norbornane moiety, are potent agonists of $upalpha$7 and $upalpha$3ast nicotinic receptors / D. Manetti, A. Garifulina, G. Bartolucci et al. // Journal of Medicinal Chemistry. — 2019. — Vol. 62, no. 4. — P. 1887–1901. 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. [ DOI ]

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