Synthesis and activity of substituted carbamates as potentiators of the alpha4beta2 nicotinic acetylcholine receptor.
The synthesis and structure-activity relationship of a series of carbamate potentiators of alpha4beta2 nAChR is reported herein. These compounds were highly selective for alpha4beta2 over other nAChR subtypes. In addition, compounds increased the response of alpha4beta2 nAChRs to acetylcholine, as measured with patch-clamp electrophysiology.
Springer
Stephanie K
SK
Department of Medicinal Chemistry, Amgen Inc., 1 Kendall Square, Building 1000, Cambridge, MA, USA. stephanie.springer@amgen.com
Woodin
Katrina S
KS
Berry
Virginia
V
Boezio
Alessandro A
AA
Cao
Lei
L
Clarkin
Kristie
K
Harmange
Jean-Christophe
JC
Hierl
Markus
M
Knop
Johannes
J
Malmberg
Annika B
AB
McDermott
Jeff S
JS
Nguyen
Hung Q
HQ
Waldon
Daniel
D
Albrecht
Brian K
BK
McDonough
Stefan I
SI
D000109:Acetylcholine / Q000737:chemistry; D002118:Calcium / Q000737:chemistry; D002219:Carbamates / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015195:Drug Design; D006801:Humans; D008956:Models, Chemical; D009420:Nervous System / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D018408:Patch-Clamp Techniques; D011720:Pyrazoles / Q000737:chemistry; D011725:Pyridines / Q000737:chemistry; D011978:Receptors, Nicotinic / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship
D002219:Carbamates; D011720:Pyrazoles; D011725:Pyridines; D011978:Receptors, Nicotinic; C403531:nicotinic receptor alpha4beta2; D000109:Acetylcholine; D002118:Calcium