TY - JOUR
T1 - Insights on the role of boron containing moieties in the design of new potent and efficient agonists targeting the β2 adrenoceptor
AU - Soriano-Ursúa, Marvin A.
AU - Arias-Montaño, José A.
AU - Correa-Basurto, José
AU - Hernández-Martínez, Christian F.
AU - López-Cabrera, Yessica
AU - Castillo-Hernández, Maria C.
AU - Padilla-Martínez, Itzia I.
AU - Trujillo-Ferrara, José G.
N1 - Publisher Copyright:
© 2014 Elsevier Ltd. All rights reserved.
PY - 2015/2/15
Y1 - 2015/2/15
N2 - The development of β2 adrenoceptor (β2AR) agonists is of increasing interest because of their wide-ranging applications in medicine, particularly for the treatment of pulmonary diseases. Regarding the relaxation of smooth muscle that lines airways of mammals, some boron-containing adducts have demonstrated greater potency and efficacy compared to well-known boron-free compounds. We herein report the design and synthesis as well as the chemical and pharmacological characterization of a new boron-containing compound: ((R)-6-((S)-2-(tert-butylammonio)-1-hydroxyethyl)-2-hydroxy-2-isobutyl-4H-benzo[d][1,3,2] dioxaborinin-2-uide). Compared to its precursor (salbutamol), this compound induced relaxation of smooth muscle in guinea pig tracheal rings with greater potency and efficacy (EC50 ≤ 28.02 nM). Theoretical studies suggest the potential selectivity of this boron containing compound on the orthosteric site of beta adrenoceptors and/or signaling pathways, as well as the importance of the tetracoordinated boron atom in its structure for binding recognition properties.
AB - The development of β2 adrenoceptor (β2AR) agonists is of increasing interest because of their wide-ranging applications in medicine, particularly for the treatment of pulmonary diseases. Regarding the relaxation of smooth muscle that lines airways of mammals, some boron-containing adducts have demonstrated greater potency and efficacy compared to well-known boron-free compounds. We herein report the design and synthesis as well as the chemical and pharmacological characterization of a new boron-containing compound: ((R)-6-((S)-2-(tert-butylammonio)-1-hydroxyethyl)-2-hydroxy-2-isobutyl-4H-benzo[d][1,3,2] dioxaborinin-2-uide). Compared to its precursor (salbutamol), this compound induced relaxation of smooth muscle in guinea pig tracheal rings with greater potency and efficacy (EC50 ≤ 28.02 nM). Theoretical studies suggest the potential selectivity of this boron containing compound on the orthosteric site of beta adrenoceptors and/or signaling pathways, as well as the importance of the tetracoordinated boron atom in its structure for binding recognition properties.
KW - Boron
KW - Bronchodilator
KW - Docking
KW - GPCRs
KW - Guinea pig
KW - β adrenoceptor agonist
UR - http://www.scopus.com/inward/record.url?scp=84964301741&partnerID=8YFLogxK
U2 - 10.1016/j.bmcl.2014.12.077
DO - 10.1016/j.bmcl.2014.12.077
M3 - Artículo
SN - 0960-894X
VL - 25
SP - 820
EP - 825
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
IS - 4
ER -