2-(Pyrrolidin-1-yl)ethyl-3,4-dihydroisoquinolin-1(<i>2H</i>)-one Derivatives as Potent and Selective Histamine-3 Receptor Antagonists

On the basis of the previously reported benzimidazole 1,3′-bipyrrolidine benzamides (<b>1</b>), a new class of 2-(pyrrolidin-1-yl)­ethyl-3,4-dihydroisoquinolin-1­(2<i>H</i>)-one derivatives (<b>3</b>–<b>50</b>) were synthesized and evaluated as potent H₃ receptor antagonists. In particular, compound <b>39</b> 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