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

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

Research output: Contribution to journal › Article › peer-review

14 Scopus citations

Abstract

We tested a set of boron containing arylethanolamine derivatives on the human and guinea pig β₂ adrenoceptor (β₂AR) 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 β₂AR agonist action of boronterol.

Original language	English
Pages (from-to)	5623-5629
Number of pages	7
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	20
Issue number	19
DOIs	https://doi.org/10.1016/j.bmcl.2010.08.040
State	Published - 1 Oct 2010

Keywords

Boron
Boronterol
Docking
Guinea pig
Salbutamol derivative
β adrenoceptor agonist

Access to Document

10.1016/j.bmcl.2010.08.040

Fingerprint

Dive into the research topics of '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'. Together they form a unique fingerprint.

Cite this

Soriano-Ursúa, M. A., Correa-Basurto, J., Valencia-Hernández, I., Amezcua-Gutiérrez, M. A., Padilla-Martínez, I. I., & Trujillo-Ferrara, J. G. (2010). 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. Bioorganic and Medicinal Chemistry Letters, 20(19), 5623-5629. https://doi.org/10.1016/j.bmcl.2010.08.040

Soriano-Ursúa, Marvin A. ; Correa-Basurto, José ; Valencia-Hernández, Ignacio et al. / 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. In: Bioorganic and Medicinal Chemistry Letters. 2010 ; Vol. 20, No. 19. pp. 5623-5629.

@article{43b15eeac8324d3ea21cc17c7f872803,

title = "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",

abstract = "We tested a set of boron containing arylethanolamine derivatives on the human and guinea pig β2 adrenoceptor (β2AR) 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 β2AR agonist action of boronterol.",

keywords = "Boron, Boronterol, Docking, Guinea pig, Salbutamol derivative, β adrenoceptor agonist",

author = "Soriano-Urs{\'u}a, {Marvin A.} and Jos{\'e} Correa-Basurto and Ignacio Valencia-Hern{\'a}ndez and Amezcua-Guti{\'e}rrez, {Marcos A.} and Padilla-Mart{\'i}nez, {Itzia I.} and Trujillo-Ferrara, {Jos{\'e} G.}",

note = "Funding Information: The authors thank the Comisi{\'o}n de Operaci{\'o}n y Fomento de Actividades Acad{\'e}micas (COFAA) , the Secretar{\'i}a de Investigaci{\'o}n y Posgrado del IPN ( 20100220 ), and the Consejo Nacional de Ciencia y Tecnolog{\'i}a ( CONACyT 62488 ) for support and scholarships. We thank Fabiola Jimena Cipr{\'e}s Flores, Luis A. Olgu{\'i}n Contreras and Cristobal Villavicencio Nava for their assistance in the experiments, Dr. Elena Vargas-D{\'i}az for helping in the polarimetry study, and Bruce Allan Larsen for his review of the use of English in the manuscript. The computer hardware used in this study was purchased with CONACyT-INNOVAPyME program support (110703). ",

year = "2010",

month = oct,

day = "1",

doi = "10.1016/j.bmcl.2010.08.040",

language = "Ingl{\'e}s",

volume = "20",

pages = "5623--5629",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

number = "19",

}

Soriano-Ursúa, MA , Correa-Basurto, J , Valencia-Hernández, I, Amezcua-Gutiérrez, MA, Padilla-Martínez, II & Trujillo-Ferrara, JG 2010, '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', Bioorganic and Medicinal Chemistry Letters, vol. 20, no. 19, pp. 5623-5629. https://doi.org/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. / Soriano-Ursúa, Marvin A.; Correa-Basurto, José ; Valencia-Hernández, Ignacio et al.
In: Bioorganic and Medicinal Chemistry Letters, Vol. 20, No. 19, 01.10.2010, p. 5623-5629.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Design, synthesis and in vitro evaluation of (R)-4-(2-(tert-butylamino)-1- hydroxyethyl)-2-(hydroxymethyl)phenyl hydrogen phenylboronate

T2 - A novel salbutamol derivative with high intrinsic efficacy on the β2 adrenoceptor

AU - Soriano-Ursúa, Marvin A.

AU - Correa-Basurto, José

AU - Valencia-Hernández, Ignacio

AU - Amezcua-Gutiérrez, Marcos A.

AU - Padilla-Martínez, Itzia I.

AU - Trujillo-Ferrara, José G.

N1 - Funding Information: The authors thank the Comisión de Operación y Fomento de Actividades Académicas (COFAA) , the Secretaría de Investigación y Posgrado del IPN ( 20100220 ), and the Consejo Nacional de Ciencia y Tecnología ( CONACyT 62488 ) for support and scholarships. We thank Fabiola Jimena Ciprés Flores, Luis A. Olguín Contreras and Cristobal Villavicencio Nava for their assistance in the experiments, Dr. Elena Vargas-Díaz for helping in the polarimetry study, and Bruce Allan Larsen for his review of the use of English in the manuscript. The computer hardware used in this study was purchased with CONACyT-INNOVAPyME program support (110703).

PY - 2010/10/1

Y1 - 2010/10/1

N2 - We tested a set of boron containing arylethanolamine derivatives on the human and guinea pig β2 adrenoceptor (β2AR) 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 β2AR agonist action of boronterol.

AB - We tested a set of boron containing arylethanolamine derivatives on the human and guinea pig β2 adrenoceptor (β2AR) 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 β2AR agonist action of boronterol.

KW - Boron

KW - Boronterol

KW - Docking

KW - Guinea pig

KW - Salbutamol derivative

KW - β adrenoceptor agonist

UR - http://www.scopus.com/inward/record.url?scp=77957562385&partnerID=8YFLogxK

U2 - 10.1016/j.bmcl.2010.08.040

DO - 10.1016/j.bmcl.2010.08.040

M3 - Artículo

C2 - 20805027

SN - 0960-894X

VL - 20

SP - 5623

EP - 5629

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 19

ER -

Soriano-Ursúa MA , Correa-Basurto J , Valencia-Hernández I, Amezcua-Gutiérrez MA, Padilla-Martínez II , Trujillo-Ferrara JG. 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. Bioorganic and Medicinal Chemistry Letters. 2010 Oct 1;20(19):5623-5629. doi: 10.1016/j.bmcl.2010.08.040