Discovery and Characterization of 4‘-(2-Furyl)-<i>N</i>-pyridin-3-yl-4,5‘-bipyrimidin-2‘-amine (LAS38096), a Potent, Selective, and Efficacious A_2BAdenosine 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.