European Journal of Medicinal Chemistry p. 875 - 888 (1996)
Update date:2022-07-30
Topics:
Dukat, M.
Fiedler, W.
Dumas, D.
Damaj, I.
Martin, B. R.
et al.
Because the structural requirements for the binding of nicotine to central nicotine receptors remain largely uninvestigated, we undertook a systematic investigation of pyrrolidine ring-opened analogs.This led to a subsequent investigation of related conformationally restricted derivatives of these analogs.The results are reported relative to the binding of several well-known and widely used nicotine receptor ligands.Although none of the ring-opened analogs binds with higher affinity than (-)-nicotine (Ki = 2.3 nM), 3-(N-methyl-N-ethylaminomethyl)pyridine (12a; Ki = 28 nM) binds with significant affinity.A conformationally restricted analog of 12a, N-methyl <2,7>naphthyridine 30b (Ki = 18 nM), binds with similar affinity. 6-Substitution of 12a and racemic nicotine seems to be tolerated when the substituent is halogen or methyl.In functional studies (hypolocomotion and antinociception in mice; stimulus generalization in nicotine-trained rats) 30b retains nicotine-like properties.Several of the 6-substituted compounds were 2 to 20 times more potent than (+/-)nicotine.Although the intact pyrrolidine ring of nicotine appears important for optimal affinity, its presence is not an absolute requirement for activity, and 6-position substitution of the pyridine nucleus can influence both binding and functional activity. - Keywords: nicotine; nicotine receptor; drug discrimination; antinociception.
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Doi:10.1021/ja9620595
(1997)Doi:10.1139/v96-240
(1996)Doi:10.1016/S0957-4166(96)00445-4
(1996)Doi:10.1021/ja963067o
(1997)Doi:10.1016/S0022-328X(96)06551-5
(1996)Doi:10.1039/p19960002793
(1996)