title: Preparation of 3-spirocyclic indolin-2-ones as ligands for the ORL-1 receptor.
abstract: A novel series of indolin-2-ones having a spirocyclic piperidine ring at the 3-position was synthesized and found to bind with high affinity to the ORL-1 receptor. Structure-activity relationships at the piperidine nitrogen were investigated. Substitution on the phenyl ring and nitrogen atom of the indolin-2-one core generated several selective high-affinity ligands that were antagonists of the ORL-1 receptor.
authors.affiliation: Johnson & Johnson Pharmaceutical Research and Development, L.L.C, PO Box 300, 1000 Route 202, Raritan, NJ 08869, USA. gbignan@prdus.jnj.com
authors.forename: Gilles C
authors.initials: GC
authors.lastname: Bignan
authors.forename: Kathleen
authors.initials: K
authors.lastname: Battista
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Connolly
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Orsini
authors.forename: Jingchun
authors.initials: J
authors.lastname: Liu
authors.forename: Steven A
authors.initials: SA
authors.lastname: Middleton
authors.forename: Allen B
authors.initials: AB
authors.lastname: Reitz
mesh_terms: D000085:Acetates / Q000737:chemistry; D002460:Cell Line; D003500:Cyclization; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D008024:Ligands; D015394:Molecular Structure; D009292:Narcotic Antagonists; D011957:Receptors, Opioid / Q000378:metabolism*; D013329:Structure-Activity Relationship; D000094942:Nociceptin Receptor
chemical_list: D000085:Acetates; D007211:Indoles; D008024:Ligands; D009292:Narcotic Antagonists; D011957:Receptors, Opioid; C456900:indolin-2-one; D000094942:Nociceptin Receptor; C000722283:OPRL1 protein, human