Discovery and characterization of 4'-(2-furyl)-N-pyridin-3-yl-4,5'-bipyrimidin-2'-amine (LAS38096), a potent, selective, and efficacious A2B adenosine receptor antagonist.
A novel series of N-heteroaryl 4'-(2-furyl)-4,5'-bipyrimidin-2'-amines has been identified as potent and selective A(2B) adenosine receptor antagonists. In particular, compound 5 showed high affinity for the A(2B) receptor (Ki = 17 nM), good selectivity (IC(50): A(1) > 1000 nM, A(2A) > 2500 nM, A3 > 1000 nM), displayed a favorable pharmacokinetic profile in preclinical species, and showed efficacy in functional in vitro models.
Vidal
Bernat
B
Almirall Research Center, Almirall, Ctra. Laureà Miró 408, E-08980 St. Feliu de Llobregat, Barcelona, Spain. bernat.vidal@almirall.es
Nueda
Arsenio
A
Esteve
Cristina
C
Domenech
Teresa
T
Benito
Sonia
S
Reinoso
Raquel F
RF
Pont
Mercè
M
Calbet
Marta
M
López
Rosa
R
Cadavid
María Isabel
MI
Loza
María Isabel
MI
Cárdenas
Alvaro
A
Godessart
Núria
N
Beleta
Jorge
J
Warrellow
Graham
G
Ryder
Hamish
H
D058917:Adenosine A2 Receptor Antagonists; D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D004285:Dogs; D005663:Furans / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D051379:Mice; D011725:Pyridines / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D013329:Structure-Activity Relationship
C520851:4'-(2-furyl)-N-pyridin-3-yl-4,5'-bipyrimidin-2'-amine; D058917:Adenosine A2 Receptor Antagonists; D005663:Furans; D011725:Pyridines; D011743:Pyrimidines