rac-6-hydroxy-8-(1-hydroxy-2-(1-(3-methoxyphenyl)-2-methylpropan-2-ylamino)ethyl)-2H-benzo[b][1,4]oxazin-3(4H)-one | 1218792-81-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶嗪类
• 英文名称: rac-6-hydroxy-8-(1-hydroxy-2-(1-(3-methoxyphenyl)-2-methylpropan-2-ylamino)ethyl)-2H-benzo[b][1,4]oxazin-3(4H)-one
• 英文别名: 6-hydroxy-8-[1-hydroxy-2-[[1-(3-methoxyphenyl)-2-methylpropan-2-yl]amino]ethyl]-4H-1,4-benzoxazin-3-one
• CAS: 1218792-81-4
• 化学式: C₂₁H₂₆N₂O₅
• 分子量: 386.448
• InChiKey: DTNVYZQGITUDPJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  28
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  100
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  甲醇 、 在 亚硝酸特丁酯 、 硫酸 作用下， 生成 rac-6-hydroxy-8-(1-hydroxy-2-(1-(3-methoxyphenyl)-2-methylpropan-2-ylamino)ethyl)-2H-benzo[b][1,4]oxazin-3(4H)-one
  参考文献：
  名称：

  Discovery of olodaterol, a novel inhaled β2-adrenoceptor agonist with a 24h bronchodilatory efficacy

  摘要：

  Compound 4p was identified from a series of 6-hydroxy-4H-benzo[1,4]oxazin-3-ones as potent agonist of the human beta(2)-adrenoceptor with a high beta(1)/beta(2)-selectivity. A complete reversal of acetylcholine-induced bronchoconstriction which lasted over the whole study period of 5 h was demonstrated for 4p in a guinea pig in vivo model without any signs of cardiovascular effects up to 10-fold above the first dose reaching 100% bronchoprotection. The enantiomerically pure (R)-form of 4p exerted a bronchodilatory efficacy over 24 h in dogs and guinea pigs in the absence of systemic pharmacodynamic effects. Formoterol which was tested as comparator in the same in vivo models of acetylcholine-induced bronchoconstriction did not retain efficacy after 24 h. In summary, the preclinical pro. le of compound (R)-4p (olodaterol, also known as BI 1744 CL) suggests a potential for once-daily dosing in man accompanied with an improved safety pro. le. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.12.087

文献信息

• Discovery of olodaterol, a novel inhaled β2-adrenoceptor agonist with a 24h bronchodilatory efficacy
  作者：Thierry Bouyssou、Christoph Hoenke、Klaus Rudolf、Philipp Lustenberger、Sabine Pestel、Peter Sieger、Ralf Lotz、Claudia Heine、Frank H. Büttner、Andreas Schnapp、Ingo Konetzki

  DOI：10.1016/j.bmcl.2009.12.087

  日期：2010.2

  Compound 4p was identified from a series of 6-hydroxy-4H-benzo[1,4]oxazin-3-ones as potent agonist of the human beta(2)-adrenoceptor with a high beta(1)/beta(2)-selectivity. A complete reversal of acetylcholine-induced bronchoconstriction which lasted over the whole study period of 5 h was demonstrated for 4p in a guinea pig in vivo model without any signs of cardiovascular effects up to 10-fold above the first dose reaching 100% bronchoprotection. The enantiomerically pure (R)-form of 4p exerted a bronchodilatory efficacy over 24 h in dogs and guinea pigs in the absence of systemic pharmacodynamic effects. Formoterol which was tested as comparator in the same in vivo models of acetylcholine-induced bronchoconstriction did not retain efficacy after 24 h. In summary, the preclinical pro. le of compound (R)-4p (olodaterol, also known as BI 1744 CL) suggests a potential for once-daily dosing in man accompanied with an improved safety pro. le. (C) 2010 Elsevier Ltd. All rights reserved.