Discovery of N-(5,6-diarylpyridin-2-yl)amide derivatives as potent and selective A(2B) adenosine receptor antagonists.
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.
Eastwood
Paul
P
Almirall Research Center, Almirall S.A., Ctra. Laureà Miró 408, St. Feliu de Llobregat, E-08980 Barcelona, Spain. paulroberteastwood@yahoo.co.uk
Gonzalez
Jacob
J
Paredes
Sergio
S
Nueda
Arsenio
A
Domenech
Teresa
T
Alberti
Joan
J
Vidal
Bernat
B
D058917:Adenosine A2 Receptor Antagonists; D000284:Administration, Oral; D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D055808:Drug Discovery; D006801:Humans; D008862:Microsomes, Liver / Q000378:metabolism; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D051381:Rats; D043704:Receptor, Adenosine A2B / Q000378:metabolism; D013329:Structure-Activity Relationship
D058917:Adenosine A2 Receptor Antagonists; D000577:Amides; D018927:Anti-Asthmatic Agents; D011725:Pyridines; D011743:Pyrimidines; D043704:Receptor, Adenosine A2B