title: Structure-activity relationships of 3-substituted N-benzhydryl-nortropane analogs as nociceptin receptor ligands for the treatment of cough.
abstract: 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.
authors.affiliation: Department of Chemical Research-CV & CNS, Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. shu-wei.yang@spcorp.com
authors.forename: Shu-Wei
authors.initials: SW
authors.lastname: Yang
authors.forename: Ginny
authors.initials: G
authors.lastname: Ho
authors.forename: Deen
authors.initials: D
authors.lastname: Tulshian
authors.forename: William J
authors.initials: WJ
authors.lastname: Greenlee
authors.forename: Xiomara
authors.initials: X
authors.lastname: Fernandez
authors.forename: Robbie L
authors.initials: RL
authors.lastname: McLeod
authors.forename: Stephen
authors.initials: S
authors.lastname: Eckel
authors.forename: John
authors.initials: J
authors.lastname: Anthes
mesh_terms: 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
chemical_list: D008024:Ligands; D009662:Nortropanes; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor