(1Z)-But-1-en-1-ylboronic acid | 1225285-16-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 硼酸衍生物
• 英文名称: (1Z)-But-1-en-1-ylboronic acid
• 英文别名: [(Z)-but-1-enyl]boronic acid
• CAS: 1225285-16-4
• 化学式: C₄H₉BO₂
• 分子量: 99.9253
• InChiKey: KKDBUAXGGKQJNY-ARJAWSKDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.04
• 重原子数：
  7
• 可旋转键数：
  2
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  40.5
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (1Z)-But-1-en-1-ylboronic acid 、 5-n-butyl-6-bromo-2-aminoindan trifluoroacetamide 在 四(三苯基膦)钯 、 cesium fluoride 作用下， 以 乙二醇二甲醚 为溶剂， 反应 18.0h， 以45%的产率得到5-n-butyl-6-(1-butenyl)-2-aminoindan trifluoroacetamide
  参考文献：
  名称：

  The Identification of Indacaterol as an Ultralong-Acting Inhaled β₂-Adrenoceptor Agonist

  摘要：

  Following a lipophilicity-based hypothesis, an 8-hydroxyquinolinone 2-aminoindan derived series of beta(2)-adrenoceptor agonists have been prepared and evaluated for their potential as inhaled ultralong-acting bronchodilators. Determination of their activities at the human beta(2)-adrenoceptor receptor showed symmetrical substitution of the 2-aminoindan moiety at the 5- and 6-positions delivered the targeted intermediate potency and intrinsic-efficacy profiles relative to a series of clinical reference beta(2)-adrenoceptor agonists. Further assessment with an in vitro superfused electrically stimulated guinea-pig tracheal-strip assay established the onset and duration of action time courses, which could be rationalized by considering the lipophilicity, potency, and intrinsic efficacy of the compounds. From these studies the 5,6-diethylindan analogue indacaterol 1c was shown to possess a unique profile of combining a rapid onset of action with a long duration of action. Further in vivo profiling of 1c supported the long duration of action and a wide therapeutic index following administration to the lung, which led to the compound being selected as a development candidate.

  DOI：

  10.1021/jm100068m

文献信息

• The Identification of Indacaterol as an Ultralong-Acting Inhaled β₂-Adrenoceptor Agonist
  作者：François Baur、David Beattie、David Beer、David Bentley、Michelle Bradley、Ian Bruce、Steven J. Charlton、Bernard Cuenoud、Roland Ernst、Robin A. Fairhurst、Bernard Faller、David Farr、Thomas Keller、John R. Fozard、Joe Fullerton、Sheila Garman、Julia Hatto、Claire Hayden、Handan He、Colin Howes、Diana Janus、Zhengjin Jiang、Christine Lewis、Frederique Loeuillet-Ritzler、Heinz Moser、John Reilly、Alan Steward、David Sykes、Lauren Tedaldi、Alexandre Trifilieff、Morris Tweed、Simon Watson、Elke Wissler、Daniel Wyss

  DOI：10.1021/jm100068m

  日期：2010.5.13

  Following a lipophilicity-based hypothesis, an 8-hydroxyquinolinone 2-aminoindan derived series of beta(2)-adrenoceptor agonists have been prepared and evaluated for their potential as inhaled ultralong-acting bronchodilators. Determination of their activities at the human beta(2)-adrenoceptor receptor showed symmetrical substitution of the 2-aminoindan moiety at the 5- and 6-positions delivered the targeted intermediate potency and intrinsic-efficacy profiles relative to a series of clinical reference beta(2)-adrenoceptor agonists. Further assessment with an in vitro superfused electrically stimulated guinea-pig tracheal-strip assay established the onset and duration of action time courses, which could be rationalized by considering the lipophilicity, potency, and intrinsic efficacy of the compounds. From these studies the 5,6-diethylindan analogue indacaterol 1c was shown to possess a unique profile of combining a rapid onset of action with a long duration of action. Further in vivo profiling of 1c supported the long duration of action and a wide therapeutic index following administration to the lung, which led to the compound being selected as a development candidate.