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 β2 adrenoceptor.

Autor: Soriano-Ursúa MA; Departamento de Bioquímica, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón 11340, Mexico. msoriano@ipn.mx, Correa-Basurto J, Valencia-Hernández I, Amezcua-Gutiérrez MA, Padilla-Martínez II, Trujillo-Ferrara JG
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2010 Oct 01; Vol. 20 (19), pp. 5623-9. Date of Electronic Publication: 2010 Aug 12.
DOI: 10.1016/j.bmcl.2010.08.040
Abstrakt: We tested a set of boron containing arylethanolamine derivatives on the human and guinea pig β(2) adrenoceptor (β(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 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(2)AR agonist action of boronterol.
(Copyright © 2010 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: