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 beta(2) adrenoceptor

作者：Soriano Ursua Marvin A^*; Correa Basurto Jose; Valencia Hernandez Ignacio; Amezcua Gutierrez Marcos A; Padilla Martinez Itzia I; Trujillo Ferrara Jose G

来源：Bioorganic & Medicinal Chemistry Letters, 2010, 20(19): 5623-5629.

DOI：10.1016/j.bmcl.2010.08.040

• Salbutamol derivative
• Boron
• Guinea pig
• Docking
• beta(2) adrenoceptor agonist
• Boronterol

We tested a set of boron containing arylethanolamine derivatives on the human and guinea pig beta(2) adrenoceptor (beta(2)AR) 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 EC50 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 beta(2)AR agonist action of boronterol.

• 出版日期2010-10-1