Insights on the role of boron containing moieties in the design of new potent and efficient agonists targeting the β2 adrenoceptor
| Autor: | Marvin A. Soriano-Ursúa, José Correa-Basurto, Yessica López-Cabrera, Christian F. Hernández-Martínez, José A. Arias-Montaño, Maria del Carmen Castillo-Hernandez, José G. Trujillo-Ferrara, Itzia I. Padilla-Martínez |
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| Rok vydání: | 2015 |
| Předmět: |
Boron Compounds
inorganic chemicals Stereochemistry Guinea Pigs Clinical Biochemistry Pharmaceutical Science Biochemistry Adduct Guinea pig Drug Discovery medicine Animals Potency Adrenergic beta-2 Receptor Agonists Molecular Biology G protein-coupled receptor Chemistry Organic Chemistry Bronchodilator Agents Molecular Docking Simulation Docking (molecular) Salbutamol Molecular Medicine Signal transduction Selectivity medicine.drug |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 25:820-825 |
| ISSN: | 0960-894X |
| DOI: | 10.1016/j.bmcl.2014.12.077 |
| Popis: | 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⩽28.02nM). 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. |
| Databáze: | OpenAIRE |
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