Identification of 3-substituted N-benzhydryl-nortropane analogs as nociceptin receptor ligands for the management of cough and anxiety.
A series of nortropane analogs based on previously reported compound 1 have been synthesized and shown to bind to the nociceptin receptor with high affinity. The synthesis and structure-activity relationships around the C-3 nortropane substitution are described. From the SAR study and hPXR screening effort, compound 15 was identified to possess potent oral antitussive and anxiolytic-like activities in the guinea pig models.
Yang
Shu-Wei
SW
Department of Chemical Research-CV & CNS, Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
Ho
Ginny
G
Tulshian
Deen
D
Greenlee
William J
WJ
Tan
Zheng
Z
Zhang
Hongtao
H
Smith-Torhan
April
A
Fawzi
Ahmad
A
Anthes
John
J
Lu
Sherry
S
Varty
Geoffrey
G
Fernandez
Xiomara
X
McLeod
Robbie L
RL
Hey
John
J