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

Marvin A Soriano-Ursúa; José Correa-Basurto; Ignacio Valencia-Hernández; Marcos A Amezcua-Gutiérrez; Itzia I Padilla-Martínez; José G Trujillo-Ferrara

doi:10.1016/j.bmcl.2010.08.040

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

Bioorg Med Chem Lett. 2010 Oct 1;20(19):5623-9. doi: 10.1016/j.bmcl.2010.08.040. Epub 2010 Aug 12.

Authors

Marvin A Soriano-Ursúa¹, José Correa-Basurto, Ignacio Valencia-Hernández, Marcos A Amezcua-Gutiérrez, Itzia I Padilla-Martínez, José G Trujillo-Ferrara

Affiliation

¹ Departamento de Bioquímica, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón 11340, Mexico. [email protected]

PMID: 20805027
DOI: 10.1016/j.bmcl.2010.08.040

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adrenergic beta-2 Receptor Agonists / chemical synthesis*
Adrenergic beta-2 Receptor Agonists / chemistry
Adrenergic beta-2 Receptor Agonists / pharmacology
Albuterol / analogs & derivatives*
Albuterol / chemical synthesis
Albuterol / chemistry
Albuterol / pharmacology
Animals
Binding Sites
Computer Simulation
Drug Design
Guinea Pigs
Humans
Isoproterenol / pharmacology
Muscle Relaxation / drug effects
Neuromuscular Agents / chemical synthesis*
Neuromuscular Agents / chemistry
Neuromuscular Agents / pharmacology
Protein Structure, Tertiary
Receptors, Adrenergic, beta-2 / chemistry*
Receptors, Adrenergic, beta-2 / metabolism
Trachea / drug effects

Substances

(R)-4-(2-(tert-butylamino)-1-hydroxyethyl)-2-(hydroxymethyl)phenyl hydrogen phenylboronate
Adrenergic beta-2 Receptor Agonists
Neuromuscular Agents
Receptors, Adrenergic, beta-2
Isoproterenol
Albuterol