Biaryl piperidines as potent and selective delta opioid receptor ligands.
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.
Liras
Spiros
S
Neuroscience Medicinal Chemistry, Pfizer Global Research and Development, Eastern Point Road, Groton, CT 06340, USA. spiros.liras@pfizer.com
McHardy
Stanton F
SF
Allen
Martin P
MP
Segelstein
Barb E
BE
Heck
Steven D
SD
Bryce
Dianne K
DK
Schmidt
Anne W
AW
Vanase-Frawley
Michelle
M
Callegari
Ernesto
E
McLean
Stafford
S
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
D008024:Ligands; D010880:Piperidines; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu