title: Synthesis and pharmacological evaluation of 1,2-dihydrospiro[isoquinoline-4(3H),4'-piperidin]-3-ones as nociceptin receptor agonists.
abstract: Some synthesized 1,2-dihydrospiro[isoquinoline-4(3 H),4'-piperidin]-3-ones were evaluated as ligands for nociceptin receptor (NOP receptor). Their affinity was established by binding studies, and efficacy was investigated by GTP binding experiments. Selectivity toward DOP, KOP, and MOP receptors was assessed, and structural requirements affecting affinity and selectivity were remarked. Most notably, compound 6d displayed nanomolar NOP receptor affinity and showed more than 800-fold selectivity. The new structures exerted full or partial agonistic activity.
authors.affiliation: Dipartimento del Farmaco, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Roma, Italy. carlo.mustazza@iss.it
authors.forename: Carlo
authors.initials: C
authors.lastname: Mustazza
authors.forename: Anna
authors.initials: A
authors.lastname: Borioni
authors.forename: Isabella
authors.initials: I
authors.lastname: Sestili
authors.forename: Maria
authors.initials: M
authors.lastname: Sbraccia
authors.forename: Andrea
authors.initials: A
authors.lastname: Rodomonte
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Del Giudice
mesh_terms: D002460:Cell Line; D003510:Cyclohexanes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007546:Isoquinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008958:Models, Molecular; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011869:Radioligand Assay; D011957:Receptors, Opioid / Q000819:agonists*; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D000094942:Nociceptin Receptor
chemical_list: D003510:Cyclohexanes; D007546:Isoquinolines; D010880:Piperidines; D011957:Receptors, Opioid; D013141:Spiro Compounds; D000094942:Nociceptin Receptor; C000722283:OPRL1 protein, human