Discovery of potent and selective bicyclic A(2B) adenosine receptor antagonists via bioisosteric amide replacement.
Several new potent and selective A(2B) adenosine receptor antagonists have been prepared in which the aryl-amide moiety of the lead series, exemplified by 1a, has been replaced by bioisosteric bicyclic moieties. Although the majority of compounds had generally improved microsomal stability as compared to 1a, this was not translated into overall improvements in the pharmacokinetic profiles of a representative set of compounds.
Eastwood
Paul
P
Almirall Research Center, Almirall S.A., Ctra. Laureà Miró 408, E-08980 St. Feliu de Llobregat, Barcelona, Spain. paulroberteastwood@yahoo.co.uk
Gonzalez
Jacob
J
Paredes
Sergio
S
Fonquerna
Silvia
S
Cardús
Arantxa
A
Alonso
Juan Antonio
JA
Nueda
Arsenio
A
Domenech
Teresa
T
Reinoso
Raquel F
RF
Vidal
Bernat
B
D058917:Adenosine A2 Receptor Antagonists; D000577:Amides / Q000737:chemistry*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D055808:Drug Discovery; D006801:Humans; D008862:Microsomes, Liver / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D051381:Rats; D043704:Receptor, Adenosine A2B / Q000378:metabolism
D058917:Adenosine A2 Receptor Antagonists; D000577:Amides; D000893:Anti-Inflammatory Agents; D001643:Bridged Bicyclo Compounds; D043704:Receptor, Adenosine A2B; D009249:NADP