title: 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.
abstract: 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.
authors.affiliation: Almirall Research Center, Almirall, Ctra. Laureà Miró 408, E-08980 St. Feliu de Llobregat, Barcelona, Spain. bernat.vidal@almirall.es
authors.forename: Bernat
authors.initials: B
authors.lastname: Vidal
authors.forename: Arsenio
authors.initials: A
authors.lastname: Nueda
authors.forename: Cristina
authors.initials: C
authors.lastname: Esteve
authors.forename: Teresa
authors.initials: T
authors.lastname: Domenech
authors.forename: Sonia
authors.initials: S
authors.lastname: Benito
authors.forename: Raquel F
authors.initials: RF
authors.lastname: Reinoso
authors.forename: Mercè
authors.initials: M
authors.lastname: Pont
authors.forename: Marta
authors.initials: M
authors.lastname: Calbet
authors.forename: Rosa
authors.initials: R
authors.lastname: López
authors.forename: María Isabel
authors.initials: MI
authors.lastname: Cadavid
authors.forename: María Isabel
authors.initials: MI
authors.lastname: Loza
authors.forename: Alvaro
authors.initials: A
authors.lastname: Cárdenas
authors.forename: Núria
authors.initials: N
authors.lastname: Godessart
authors.forename: Jorge
authors.initials: J
authors.lastname: Beleta
authors.forename: Graham
authors.initials: G
authors.lastname: Warrellow
authors.forename: Hamish
authors.initials: H
authors.lastname: Ryder
mesh_terms: 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
chemical_list: C520851:4'-(2-furyl)-N-pyridin-3-yl-4,5'-bipyrimidin-2'-amine; D058917:Adenosine A2 Receptor Antagonists; D005663:Furans; D011725:Pyridines; D011743:Pyrimidines