3,5-Bicyclic aryl piperidines: a novel class of alpha4beta2 neuronal nicotinic receptor partial agonists for smoking cessation.
3,5-Bicyclic aryl piperidines are a new class of high-affinity alpha4beta2 nicotinic receptor agents. We have sought nicotinic receptor partial agonists of the alpha4beta2 nicotinic acetylcholine receptor for smoking cessation, and a number of compounds fulfill potency, selectivity, and efficacy requirements in vitro. In vivo, selected agents demonstrate potent partial agonist efficacy on the mesolimbic dopamine system, a key measure of therapeutic potential for smoking cessation.
Coe
Jotham W
JW
Pfizer Global Research and Development, Groton Laboratories, Eastern Point Road, Groton, CT 06340, USA. jwcoe@pfizer.com
Brooks
Paige R
PR
Wirtz
Michael C
MC
Bashore
Crystal G
CG
Bianco
Krista E
KE
Vetelino
Michael G
MG
Arnold
Eric P
EP
Lebel
Lorraine A
LA
Fox
Carol B
CB
Tingley
F David
FD
Schulz
David W
DW
Davis
Thomas I
TI
Sands
Steven B
SB
Mansbach
Robert S
RS
Rollema
Hans
H
O'Neill
Brian T
BT
D000818:Animals; D003500:Cyclization; D015394:Molecular Structure; D010880:Piperidines / Q000737:chemistry* / Q000145:classification / Q000494:pharmacology*; D051381:Rats; D011978:Receptors, Nicotinic / Q000378:metabolism*; D016540:Smoking Cessation / Q000379:methods*; D013329:Structure-Activity Relationship
D010880:Piperidines; D011978:Receptors, Nicotinic; C403531:nicotinic receptor alpha4beta2