Discovery and optimization of potent and selective functional antagonists of the human adenosine A2B receptor

We herein report the discovery of a novel class of antagonists of the human adenosine A2B receptor. This low molecular weight scaffold has been optimized to offer derivatives with potential utility for the alleviation of conditions associated with this receptor subtype, such as nociception, diabetes...

Full description

Saved in:
Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2009-10, Vol.19 (20), p.5945-5949
Main Authors: BEDFORD, Simon T, BENWELL, Karen R, KLENKE, Burkhard, LESTRAT, Loic, MERRETT, Angela, MISRA, Anil, LIGHTOWLER, Sean, PADFIELD, Anthony, POULLENNEC, Karine, REECE, Mark, SIMMONITE, Heather, WONG, Melanie, BROOKS, Teresa, YULE, Ian A, CHEN, Ijen, COMER, Mike, DUGDALE, Sarah, HAYMES, Tim, JORDAN, Allan M, KENNETT, Guy A, KNIGHT, Anthony R
Format: Article
Language:English
Subjects:
Adenosine A2 Receptor Antagonists
Administration, Inhalation
Animals
Asthma - drug therapy
Biological and medical sciences
Drug Design
Humans
Medical sciences
Neuropharmacology
Neurotransmitters. Neurotransmission. Receptors
Peptidergic system (neuropeptide, opioid peptide, opiates...). Adenosinergic and purinergic systems
Pharmacology. Drug treatments
Pulmonary Disease, Chronic Obstructive - drug therapy
Pyrimidines - chemical synthesis
Pyrimidines - chemistry
Pyrimidines - pharmacokinetics
Rats
Receptor, Adenosine A2A - metabolism
Receptor, Adenosine A2B - metabolism
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:We herein report the discovery of a novel class of antagonists of the human adenosine A2B receptor. This low molecular weight scaffold has been optimized to offer derivatives with potential utility for the alleviation of conditions associated with this receptor subtype, such as nociception, diabetes, asthma and COPD. Furthermore, preliminary pharmacokinetic analysis has revealed compounds with profiles suitable for either inhaled or systemic routes of administration.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2009.08.040