Design, synthesis and in vitro evaluation of ( R)-4-(2-( tert-butylamino)-1-hydroxyethyl)-2-(hydroxymethyl)phenyl hydrogen phenylboronate: A novel salbutamol derivative with high intrinsic efficacy on the β 2 adrenoceptor

Abstract

We tested a set of boron containing arylethanolamine derivatives on the human and guinea pig β 2 adrenoceptor (β 2AR) 3-D structures by docking methodology. The compound with the highest affinity based on docking analysis, ( R)-4-(2-( tert-butylamino)-1-hydroxyethyl)-2-(hydroxymethyl)phenyl hydrogen phenylboronate (boronterol) was synthesized, characterized and tested in guinea pig tracheal rings at basal tone and with histamine-induced contractions. Boronterol was at least eightfold more potent than salbutamol as a smooth muscle relaxant drug (judged by the EC 50 values) and showed a similar maximal relaxant effect as isoproterenol. ICI118,551 showed competitive antagonism on the relaxing effect of boronterol. These results suggest the β 2AR agonist action of boronterol.