In pursuit of alpha4beta2 nicotinic receptor partial agonists for smoking cessation: carbon analogs of (-)-cytisine.
The preparation and biological activity of analogs of (-)-cytisine, an alpha4beta2 nicotinic receptor partial agonist, are discussed. All-carbon-containing phenyl ring replacements of the pyridone ring system, generated via Heck cyclization protocols, exhibited weaker affinity and lower efficacy partial agonist profiles relative to (-)-cytisine. In vivo, selected compounds exhibit lower efficacy partial agonist profiles than that of (-)-cytisine.
Coe
Jotham W
JW
Pfizer Global Research and Development, Groton Laboratories, Eastern Point Road, Groton, CT 06340, USA. jwcoe@pfizer.com
Vetelino
Michael G
MG
Bashore
Crystal G
CG
Wirtz
Michael C
MC
Brooks
Paige R
PR
Arnold
Eric P
EP
Lebel
Lorraine A
LA
Fox
Carol B
CB
Sands
Steven B
SB
Davis
Thomas I
TI
Schulz
David W
DW
Rollema
Hans
H
Tingley
F David
FD
O'Neill
Brian T
BT
D000470:Alkaloids / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D001392:Azocines / Q000737:chemistry / Q000494:pharmacology; D002244:Carbon / Q000737:chemistry*; D004298:Dopamine / Q000378:metabolism*; D018722:Nicotinic Agonists / Q000737:chemistry / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000187:drug effects*; D011807:Quinolizines / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D011978:Receptors, Nicotinic / Q000737:chemistry* / Q000378:metabolism; D016540:Smoking Cessation; D013329:Structure-Activity Relationship; D000093843:Quinolizidine Alkaloids
D000470:Alkaloids; D001392:Azocines; D002244:Carbon; D004298:Dopamine; D018722:Nicotinic Agonists; D011807:Quinolizines; D011978:Receptors, Nicotinic; C403531:nicotinic receptor alpha4beta2; C004712:cytisine; D000093843:Quinolizidine Alkaloids