Biaryl piperidines as potent and selective delta opioid receptor ligands

Spiros Liras; Stanton F McHardy; Martin P Allen; Barb E Segelstein; Steven D Heck; Dianne K Bryce; Anne W Schmidt; Michelle Vanase-Frawley; Ernesto Callegari; Stafford McLean

doi:10.1016/j.bmcl.2009.11.113

Biaryl piperidines as potent and selective delta opioid receptor ligands

Bioorg Med Chem Lett. 2010 Jan 15;20(2):503-7. doi: 10.1016/j.bmcl.2009.11.113. Epub 2009 Nov 26.

Authors

Spiros Liras¹, Stanton F McHardy, Martin P Allen, Barb E Segelstein, Steven D Heck, Dianne K Bryce, Anne W Schmidt, Michelle Vanase-Frawley, Ernesto Callegari, Stafford McLean

Affiliation

¹ Neuroscience Medicinal Chemistry, Pfizer Global Research and Development, Eastern Point Road, Groton, CT 06340, USA. spiros.liras@pfizer.com

PMID: 20015649
DOI: 10.1016/j.bmcl.2009.11.113

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.

MeSH terms

Animals
Drug Design
Humans
Ligands*
Microsomes, Liver / metabolism
Piperidines / chemical synthesis
Piperidines / chemistry*
Piperidines / pharmacology
Protein Binding
Rats
Receptors, Opioid, delta / antagonists & inhibitors*
Receptors, Opioid, delta / metabolism
Receptors, Opioid, kappa / antagonists & inhibitors
Receptors, Opioid, kappa / metabolism
Receptors, Opioid, mu / antagonists & inhibitors
Receptors, Opioid, mu / metabolism
Structure-Activity Relationship

Substances

Ligands
Piperidines
Receptors, Opioid, delta
Receptors, Opioid, kappa
Receptors, Opioid, mu