A novel series of [3.2.1] azabicyclic biaryl ethers as alpha3beta4 and alpha6/4beta4 nicotinic receptor agonists.
We report the synthesis of a series of [3.2.1]azabicyclic biaryl ethers as selective agonists of alpha3- and alpha6-containing nicotinic receptors. In particular, compound 17a from this series is a potent alpha3beta4 and alpha6/4beta4 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 alpha3beta4 and alpha6/4beta4 nicotinic receptors in CNS pharmacology.
Lowe
John A
JA
Pfizer Global Research & Development, Eastern Point Road, Groton, CT 06340, United States. jal3rd@gmail.com
DeNinno
Shari L
SL
Coe
Jotham W
JW
Zhang
Lei
L
Mente
Scot
S
Hurst
Raymond S
RS
Mather
Robert J
RJ
Ward
Karen M
KM
Shrikhande
Alka
A
Rollema
Hans
H
Johnson
David E
DE
Horner
Weldon
W
Gorczyca
Roxanne
R
Tingley
F David
FD
Kozak
Rouba
R
Majchrzak
Mark J
MJ
Tritto
Theresa
T
Sadlier
Jen
J
Shaffer
Chris L
CL
Ellerbrock
Brenda
B
Osgood
Sarah M
SM
MacDougall
Mary C
MC
McDowell
Laura L
LL
D053961:Azabicyclo Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
D053961:Azabicyclo Compounds; D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; D013449:Sulfonamides; C427403:alpha(4)beta(4) nicotinic receptor; C403530:nicotinic receptor alpha3beta4; C104518:nicotinic receptor alpha6