Novel pyridyl ring C5 substituted analogues of epibatidine and 3-(1-methyl-2(S)-pyrrolidinylmethoxy)pyridine (A-84543) as highly selective agents for neuronal nicotinic acetylcholine receptors containing β2 subunits

Zhi Liang Wei; Yingxian Xiao; Hongbin Yuan; Maryna Baydyuk; Pavel A. Petukhov; John L. Musachio; Kenneth J. Kellar; Alan P. Kozikowski

doi:10.1021/jm0492406

Novel pyridyl ring C5 substituted analogues of epibatidine and 3-(1-methyl-2(S)-pyrrolidinylmethoxy)pyridine (A-84543) as highly selective agents for neuronal nicotinic acetylcholine receptors containing β2 subunits

Zhi Liang Wei, Yingxian Xiao, Hongbin Yuan, Maryna Baydyuk, Pavel A. Petukhov, John L. Musachio, Kenneth J. Kellar, Alan P. Kozikowski

Research output: Contribution to journal › Article › peer-review

39 Scopus citations

Abstract

Introduction of a hydrophobic or hydrogen-bonding alkynyl group into the C5 position of the pyridyl ring of epibatidine and A-84543 significantly increased the selectivity for neuronal nicotinic acetylcholine receptors (nAChRs) containing β2 subunits over nAChRs containing β4 subunits (K _i ratio up to 92000-fold). Our data indicate that the extracellular domains of the nAChRs are sufficiently different to allow for the design of novel ligands with high affinity and selectivity for the nAChR subtypes.

Original language	English (US)
Pages (from-to)	1721-1724
Number of pages	4
Journal	Journal of medicinal chemistry
Volume	48
Issue number	6
DOIs	https://doi.org/10.1021/jm0492406
State	Published - Mar 24 2005
Externally published	Yes

ASJC Scopus subject areas

Molecular Medicine
Drug Discovery

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Wei, Z. L., Xiao, Y., Yuan, H., Baydyuk, M., Petukhov, P. A., Musachio, J. L., Kellar, K. J., & Kozikowski, A. P. (2005). Novel pyridyl ring C5 substituted analogues of epibatidine and 3-(1-methyl-2(S)-pyrrolidinylmethoxy)pyridine (A-84543) as highly selective agents for neuronal nicotinic acetylcholine receptors containing β2 subunits. Journal of medicinal chemistry, 48(6), 1721-1724. https://doi.org/10.1021/jm0492406

Novel pyridyl ring C5 substituted analogues of epibatidine and 3-(1-methyl-2(S)-pyrrolidinylmethoxy)pyridine (A-84543) as highly selective agents for neuronal nicotinic acetylcholine receptors containing β2 subunits. / Wei, Zhi Liang; Xiao, Yingxian; Yuan, Hongbin et al.
In: Journal of medicinal chemistry, Vol. 48, No. 6, 24.03.2005, p. 1721-1724.

Research output: Contribution to journal › Article › peer-review

Wei, ZL, Xiao, Y, Yuan, H, Baydyuk, M, Petukhov, PA, Musachio, JL, Kellar, KJ & Kozikowski, AP 2005, 'Novel pyridyl ring C5 substituted analogues of epibatidine and 3-(1-methyl-2(S)-pyrrolidinylmethoxy)pyridine (A-84543) as highly selective agents for neuronal nicotinic acetylcholine receptors containing β2 subunits', Journal of medicinal chemistry, vol. 48, no. 6, pp. 1721-1724. https://doi.org/10.1021/jm0492406

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abstract = "Introduction of a hydrophobic or hydrogen-bonding alkynyl group into the C5 position of the pyridyl ring of epibatidine and A-84543 significantly increased the selectivity for neuronal nicotinic acetylcholine receptors (nAChRs) containing β2 subunits over nAChRs containing β4 subunits (K i ratio up to 92000-fold). Our data indicate that the extracellular domains of the nAChRs are sufficiently different to allow for the design of novel ligands with high affinity and selectivity for the nAChR subtypes.",

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AU - Wei, Zhi Liang

AU - Xiao, Yingxian

AU - Yuan, Hongbin

AU - Baydyuk, Maryna

AU - Petukhov, Pavel A.

AU - Musachio, John L.

AU - Kellar, Kenneth J.

AU - Kozikowski, Alan P.

PY - 2005/3/24

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Novel pyridyl ring C5 substituted analogues of epibatidine and 3-(1-methyl-2(S)-pyrrolidinylmethoxy)pyridine (A-84543) as highly selective agents for neuronal nicotinic acetylcholine receptors containing β2 subunits

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