Highly potent and selective zwitterionic agonists of the δ-opioid receptor. Part 1

A series of potent and selective zwitterionic δ-opioid agonists ( 2) and ( 3) are described. A series of zwitterionic δ-opioid agonists, with targeted physicochemistry, as a strategy to limit potential for CNS exposure, were prepared. These agents were found to possess exquisite potency and selectiv...

Full description

Saved in:
Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2006-02, Vol.16 (4), p.905-910
Main Authors: Middleton, Donald S., Maw, Graham N., Challenger, Clare, Jessiman, Alan, Johnson, Patrick S., Million, William A., Nichols, Carly L., Price, Jenny A., Trevethick, Michael
Format: Article
Language:English
Subjects:
Agonist
Animals
Biological and medical sciences
Dogs
Drug Design
Indoles - administration & dosage
Indoles - chemical synthesis
Indoles - pharmacology
Isoquinolines - administration & dosage
Isoquinolines - chemical synthesis
Isoquinolines - pharmacology
Medical sciences
Mice
Molecular Conformation
Molecular Weight
Neuropharmacology
Neurotransmitters. Neurotransmission. Receptors
Peptidergic system (neuropeptide, opioid peptide, opiates...). Adenosinergic and purinergic systems
Pharmacology. Drug treatments
Receptors, Opioid, delta - agonists
Structure-Activity Relationship
δ-Opioid
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:A series of potent and selective zwitterionic δ-opioid agonists ( 2) and ( 3) are described. A series of zwitterionic δ-opioid agonists, with targeted physicochemistry, as a strategy to limit potential for CNS exposure, were prepared. These agents were found to possess exquisite potency and selectivity over mu and κ-opiate activity. Furthermore, analogue 3a was found to display restricted CNS exposure, as evidenced by its inactivity in a rodent hyperlocomotion assay of central opiate activity. Dog pharmacokinetic studies on 3a indicated encouraging oral bioavailability.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2005.10.102