title: Synthesis and structure-activity relationships of N-substituted spiropiperidines as nociceptin receptor ligands: part 2.
abstract: A series of N-8 substituted analogs based upon the spiropiperidine core of the original lead compound 1 was synthesized. This lead has been elaborated to compounds to give compounds 2 and 3 (R=H) that exhibited high NOP binding affinity as well as selectivity against other known opioid receptors. These two series have been further functionalized at the amido nitrogen. The synthesis and structure-activity relationship (SAR) of these and related compounds are discussed.
authors.affiliation: CV & CNS Department of Chemical Research, Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. john.caldwell@spcorp.com
authors.forename: John P
authors.initials: JP
authors.lastname: Caldwell
authors.forename: Julius J
authors.initials: JJ
authors.lastname: Matasi
authors.forename: Xiomara
authors.initials: X
authors.lastname: Fernandez
authors.forename: Robbie L
authors.initials: RL
authors.lastname: McLeod
authors.forename: Hongtao
authors.initials: H
authors.lastname: Zhang
authors.forename: Ahmad
authors.initials: A
authors.lastname: Fawzi
authors.forename: Deen B
authors.initials: DB
authors.lastname: Tulshian
mesh_terms: D000818:Animals; D001665:Binding Sites; D002211:Capsaicin / Q000494:pharmacology; D020650:Combinatorial Chemistry Techniques; D003371:Cough / Q000139:chemically induced; D004195:Disease Models, Animal; D015195:Drug Design; D006168:Guinea Pigs; D015394:Molecular Structure; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011957:Receptors, Opioid / Q000187:drug effects* / Q000378:metabolism; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D000094942:Nociceptin Receptor
chemical_list: D010880:Piperidines; D011957:Receptors, Opioid; D013141:Spiro Compounds; D002211:Capsaicin; D000094942:Nociceptin Receptor