2-(Pyrrolidin-1-yl)ethyl-3,4-dihydroisoquinolin-1(2H)-one derivatives as potent and selective histamine-3 receptor antagonists.

On the basis of the previously reported benzimidazole 1,3′-bipyrrolidine benzamides (1), a new class of 2-(pyrrolidin-1-yl)ethyl-3,4-dihydroisoquinolin-1(2H)-one derivatives (3–50) were synthesized and evaluated as potent H3 receptor antagonists. In particular, compound 39 exhibited potent in vitro binding and functional activities at the H3 receptor, good selectivities against other neurotransmitter receptors and ion channels, acceptable pharmacokinetic properties, and a favorable in vivo profile.