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 -