title: Biaryl piperidines as potent and selective delta opioid receptor ligands.
abstract: The design and synthesis of novel opiates are reported. Based on the message-address principle a novel class of 4,4- and 3,3-biaryl piperidines was designed and synthesized. Biological evaluation confirmed that these compounds exhibit high affinity and selectivity for the delta opioid receptor. Key structure-activity relationships that influence affinity, selectivity, functional activity and clearance are reported.
authors.affiliation: Neuroscience Medicinal Chemistry, Pfizer Global Research and Development, Eastern Point Road, Groton, CT 06340, USA. spiros.liras@pfizer.com
authors.forename: Spiros
authors.initials: S
authors.lastname: Liras
authors.forename: Stanton F
authors.initials: SF
authors.lastname: McHardy
authors.forename: Martin P
authors.initials: MP
authors.lastname: Allen
authors.forename: Barb E
authors.initials: BE
authors.lastname: Segelstein
authors.forename: Steven D
authors.initials: SD
authors.lastname: Heck
authors.forename: Dianne K
authors.initials: DK
authors.lastname: Bryce
authors.forename: Anne W
authors.initials: AW
authors.lastname: Schmidt
authors.forename: Michelle
authors.initials: M
authors.lastname: Vanase-Frawley
authors.forename: Ernesto
authors.initials: E
authors.lastname: Callegari
authors.forename: Stafford
authors.initials: S
authors.lastname: McLean
mesh_terms: D000818:Animals; D015195:Drug Design; D006801:Humans; D008024:Ligands; D008862:Microsomes, Liver / Q000378:metabolism; D010880:Piperidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011485:Protein Binding; D051381:Rats; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors* / Q000378:metabolism; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D008024:Ligands; D010880:Piperidines; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu