185510-44-5Relevant articles and documents
Microwave-assisted iridium-catalyzed synthesis of nicotine and anabasine derivatives
Apsunde, Tushar Dattu,Trudell, Mark L.
, p. 2120 - 2124 (2013/08/23)
Various functionalized nicotine and anabasine analogues are synthesized via a three-step sequence that exploits a microwave-assisted iridium-catalyzed N-heterocyclization of 1,4- and 1,5-diols for the construction of the pyrrolidine and piperidine ring systems. The microwave-assisted N-heterocyclization furnishes derivatives of nicotine and anabasine in good yields (50-75%) with overall yields ranging from 30-50%. Georg Thieme Verlag Stuttgart. New York.
Pyrrolidine-modified and 6-substituted analogs of nicotine: a structure-affinity investigation
Dukat, M.,Fiedler, W.,Dumas, D.,Damaj, I.,Martin, B. R.,et al.
, p. 875 - 888 (2007/10/03)
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 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.
