426463-16-3Relevant articles and documents
Compounds and methods for promoting smoking cessation
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, (2008/06/13)
Compounds and methods for promoting smoking cessation. The compounds may be used to treat a variety of other conditions and disease states.
Synthesis, nicotinic acetylcholine receptor binding, and antinociceptive properties of 2-exo-2-(2′,3′-disubstituted 5′-pyridinyl)-7-azabicyclo[2.2.1]heptanes: Epibatidine analogues
Carroll, F. Ivy,Lee, Jeffrey R.,Navarro, Hernán A.,Ma, Wei,Brieaddy, Lawrence E.,Abraham, Philip,Damaj,Martin, Billy R.
, p. 4755 - 4761 (2007/10/03)
A number of 2′,3′-disubstituted epibatidine analogues were synthesized and evaluated in vitro for potency at nicotinic acetylcholine receptors (nAChRs) and in vivo for antinociception activity in the tail-flick and hot-plate models of acute pain and for their ability to affect core body temperature. Compounds that possessed electron-withdrawing groups (F, Cl, Br, and I) in both the 2′- and the 3′-positions showed affinities at the nAChR similar to epibatidine. However, in vivo efficacy did not correlate with affinity. 2-exo-(3′-Amino-2′-chloro-5′- pyridinyl)-7-azabicyclo-[2.2.1]heptane (2i), an epibatidine analogue possessing an electron-releasing amino group in the 3′-position, produced the highest affinity. Compound 2i was also the most selective epibatidine analogue with a Ki of 0.001 nM at αβ nAChRs, which is 26 times greater than that of epibatidine, and a αβ/α7 Ki ratio of 14 000, twice that of epibatidine. In vivo testing revealed that this compound potently inhibited nicotine-induced antinociception with AD50 values below 1 μg/kg. Surprisingly, this same compound was also an agonist at higher doses (ED50 ～20 μg/kg). Thus, the addition of the 3′-amino group to epibatidine confers potent antagonist activity to the compound with little effect on agonist activity. 2,3-Disubstituted epibatidine analogues possessing a 2′-amino group combined with a 3′-bromo or 3′-iodo group showed in vitro and in vivo nAChR properties similar to nicotine.
