Discovery and characterization of 4 '-(2-Furyl)-N-pyridin-3-yl-4,5 '-bipyrimidin-2 '-amine (LAS38096), a potent, selective, and efficacious A(2B) adenosine receptor antagonist

摘要

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 (K-i = 17 nM), good selectivity (IC50: A(1) > 1000 nM, A(2A) > 2500 nM, A(3) > 1000 nM), displayed a favorable pharmacokinetic profile in preclinical species, and showed efficacy in functional in vitro models.