Discovery of N-(5,6-diarylpyridin-2-yl)amide derivatives as potent and selective A(2B) adenosine receptor antagonists

Paul Eastwood; Jacob Gonzalez; Sergio Paredes; Arsenio Nueda; Teresa Domenech; Joan Alberti; Bernat Vidal

doi:10.1016/j.bmcl.2010.01.045

Discovery of N-(5,6-diarylpyridin-2-yl)amide derivatives as potent and selective A(2B) adenosine receptor antagonists

Bioorg Med Chem Lett. 2010 Mar 1;20(5):1697-700. doi: 10.1016/j.bmcl.2010.01.045. Epub 2010 Jan 20.

Authors

Paul Eastwood¹, Jacob Gonzalez, Sergio Paredes, Arsenio Nueda, Teresa Domenech, Joan Alberti, Bernat Vidal

Affiliation

¹ Almirall Research Center, Almirall S.A., Ctra. Laureà Miró 408, St. Feliu de Llobregat, E-08980 Barcelona, Spain. paulroberteastwood@yahoo.co.uk

PMID: 20137946
DOI: 10.1016/j.bmcl.2010.01.045

Abstract

The synthesis and SAR of a series of N-(5,6-diarylpyridin-2-yl)amide derivatives as potent A(2B) adenosine receptor antagonists is described. Several compounds showed good selectivity versus other adenosine receptors. The potent and selective analogue 9 was shown to have good oral bioavailability in the rat.

MeSH terms

Adenosine A2 Receptor Antagonists*
Administration, Oral
Amides / chemical synthesis
Amides / chemistry*
Amides / pharmacokinetics
Animals
Anti-Asthmatic Agents / chemical synthesis
Anti-Asthmatic Agents / chemistry*
Anti-Asthmatic Agents / pharmacokinetics
Drug Discovery
Humans
Microsomes, Liver / metabolism
Pyridines / chemical synthesis
Pyridines / chemistry*
Pyridines / pharmacology
Pyrimidines / chemical synthesis
Pyrimidines / chemistry*
Pyrimidines / pharmacology
Rats
Receptor, Adenosine A2B / metabolism
Structure-Activity Relationship

Substances

Adenosine A2 Receptor Antagonists
Amides
Anti-Asthmatic Agents
Pyridines
Pyrimidines
Receptor, Adenosine A2B