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

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• 作者：Marvin A. Soriano-Ursú ; a ; José ; Correa-Basurto ; Ignacio Valencia-Herná ; ndez ; Marcos A. Amezcua-Gutié ; rrez ; Itzia I. Padilla-Martí ; nez ; José ; G. Trujillo-Ferrara
• 关键词：Salbutamol derivative ; Boron ; Guinea pig ; Docking ; β ; ₂ adrenoceptor agonist ; Boronterol
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2010
• 出版时间：1 October 2010
• 年：2010
• 卷：20
• 期：19
• 页码：5623-5629
• 全文大小：745 K

文摘

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.