Structure-activity relationships of 3-substituted N-benzhydryl-nortropane analogs as nociceptin receptor ligands for the treatment of cough.
A series of 3-axial-aminomethyl-N-benzhydryl-nortropane analogs have been synthesized and identified to bind to the nociceptin receptor with high affinity. Many of these analogs showed high binding selectivity over classic opioid receptors such as mu receptor. The synthesis and structure-activity relationships around the C-3 nortropane substitution are described. Selected compounds with potent oral antitussive activity in the guinea pig model are disclosed.
Yang
Shu-Wei
SW
Department of Chemical Research-CV & CNS, Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. shu-wei.yang@spcorp.com
Ho
Ginny
G
Tulshian
Deen
D
Greenlee
William J
WJ
Fernandez
Xiomara
X
McLeod
Robbie L
RL
Eckel
Stephen
S
Anthes
John
J
D000818:Animals; D016466:CHO Cells; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003371:Cough / Q000188:drug therapy* / Q000473:pathology; D006224:Cricetinae; D003412:Cricetulus; D015195:Drug Design; D006168:Guinea Pigs; D007700:Kinetics; D008024:Ligands; D008956:Models, Chemical; D009662:Nortropanes / Q000138:chemical synthesis* / Q000378:metabolism; D011957:Receptors, Opioid / Q000737:chemistry*; D013329:Structure-Activity Relationship; D000094942:Nociceptin Receptor
D008024:Ligands; D009662:Nortropanes; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor