A novel series of [3.2.1] azabicyclic biaryl ethers as α3β4 and α6/4β4 nicotinic receptor agonists

被引：9

作者：

Lowe, John A., III ^{[1
]}

DeNinno, Shari L. ^{[1
]}

Coe, Jotham W. ^{[1
]}

Zhang, Lei ^{[1
]}

Mente, Scot ^{[1
]}

Hurst, Raymond S. ^{[1
]}

Mather, Robert J. ^{[1
]}

Ward, Karen M. ^{[1
]}

Shrikhande, Alka ^{[1
]}

Rollema, Hans ^{[1
]}

Johnson, David E. ^{[1
]}

Horner, Weldon ^{[1
]}

Gorczyca, Roxanne ^{[1
]}

Tingley, F. David, III ^{[1
]}

Kozak, Rouba ^{[1
]}

Majchrzak, Mark J. ^{[1
]}

Tritto, Theresa ^{[1
]}

Sadlier, Jen ^{[1
]}

Shaffer, Chris L. ^{[1
]}

Ellerbrock, Brenda ^{[1
]}

Osgood, Sarah M. ^{[1
]}

MacDougall, Mary C. ^{[1
]}

McDowell, Laura L. ^{[1
]}

机构：

[1] Pfizer Global Res & Dev, Groton, CT 06340 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2010年 / 20卷 / 16期

关键词：

Nicotinic; Receptor; Agonist; Alpha-6; Alpha-3; Schizophrenia; ACETYLCHOLINE-RECEPTORS; SMOKING-CESSATION; VARENICLINE;

D O I：

10.1016/j.bmcl.2010.06.142

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

We report the synthesis of a series of [3.2.1]azabicyclic biaryl ethers as selective agonists of alpha 3- and alpha 6-containing nicotinic receptors. In particular, compound 17a from this series is a potent alpha 3 beta 4 and alpha 6/4 beta 4 receptor agonist in terms of both binding and functional activity. Compound 17a also shows potent in vivo activity in CNS-mediated animal models that are sensitive to antipsychotic drugs. Compound 17a may thus be a useful tool for studying the role of alpha 3 beta 4 and alpha 6/4 beta 4 nicotinic receptors in CNS pharmacology. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：4749 / 4752

页数：4

共 50 条

[1] Award Address (ACS Award in Industrial Chemistry sponsored by ACS Division of Business Development and Management and the Society of Chemical Manufacturers and Affiliates, Inc. (SOCMA)). Discovery of a novel series of [3.2.1] azabicyclic biaryl ethers as α3β4 and α6/4β4 nicotinic receptor agonists
Lowe, John A., III
DeNinno, Shari L.
Coe, Jotham W.
Zhang, Lei
Mente, Scot
Hurst, Raymond S.
Mather, Robert J.
Ward, Karen M.
Shrikhande, Alka
Rollema, Hans
Johnson, David E.
Horner, Weldon
Gorczyca, Roxanne
Tingley, Gorczyca F. David, III
Kozak, Rouba
Majchrzak, Mark J.
Tritto, Teresa
Sadlier, Jen
Shaffer, Chris L.
Ellerbrock, Brenda
Osgood, Sarah M.
MacDougall, Mary C.
McDowell, Laura L.
[J]. ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2011, 241
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