7-[(1R)-2-[2-(3-butoxyphenyl)ethylamino]-1-hydroxyethyl]-4-hydroxy-3H-1,3-benzothiazol-2-one | 663924-41-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻唑类
• 英文名称: 7-[(1R)-2-[2-(3-butoxyphenyl)ethylamino]-1-hydroxyethyl]-4-hydroxy-3H-1,3-benzothiazol-2-one
• CAS: 663924-41-2
• 化学式: C₂₁H₂₆N₂O₄S
• 分子量: 402.514
• InChiKey: OMKRQXYKQXMQEL-SFHVURJKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  28
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  116
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  3-羟基苯乙酸 在 甲酸 、 丙酮腈 、 二异丁基氢化铝 、 1-羟基苯并三唑 、 caesium carbonate 、 钯 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 potassium iodide 作用下， 以 二氯甲烷 、 水 、 甲苯 为溶剂， 反应 68.0h， 生成 7-[(1R)-2-[2-(3-butoxyphenyl)ethylamino]-1-hydroxyethyl]-4-hydroxy-3H-1,3-benzothiazol-2-one
  参考文献：
  名称：

  The identification of 7-[(R)-2-((1S,2S)-2-benzyloxycyclopentylamino)-1-hydroxyethyl]-4-hydroxybenzothiazolone as an inhaled long-acting β2-adrenoceptor agonist

  摘要：

  The optimisation of two series of 4-hydroxybenzothiazolone derived β2-adrenoceptor agonists, bearing α-substituted cyclopentyl and β-phenethyl amino-substituents, as inhaled long-acting bronchodilators is described. Analogues were selected for synthesis using a lipophilicity based hypothesis to achieve the targeted rapid onset of action in combination with a long duration of action. The profiling of the two series led to identification of the α-substituted cyclopentyl analogue 2 as the optimal compound with a comparable profile to the inhaled once-daily long-acting β2-adrenoceptor agonist indacaterol. On the basis of these data 2 was promoted as the backup development candidate to indacaterol from the Novartis LABA project.

  DOI：

  10.1016/j.bmcl.2014.06.014

文献信息

• The identification of 7-[(R)-2-((1S,2S)-2-benzyloxycyclopentylamino)-1-hydroxyethyl]-4-hydroxybenzothiazolone as an inhaled long-acting β2-adrenoceptor agonist
  作者：Nicola Arnold、David Beattie、Michelle Bradley、Andrew Brearley、Lyndon Brown、Steven J. Charlton、Robin A. Fairhurst、David Farr、John Fozard、Joe Fullerton、Martin Gosling、Julia Hatto、Diana Janus、Darryl Jones、Lynne Jordan、Christine Lewis、Janet Maas、Clive McCarthy、Mark Mercer、Helen Oakman、Neil Press、Rachel Profit、Friedrich Schuerch、David Sykes、Roger J. Taylor、Alexandre Trifilieff、Andrew Tuffnell

  DOI：10.1016/j.bmcl.2014.06.014

  日期：2014.9

  The optimisation of two series of 4-hydroxybenzothiazolone derived β2-adrenoceptor agonists, bearing α-substituted cyclopentyl and β-phenethyl amino-substituents, as inhaled long-acting bronchodilators is described. Analogues were selected for synthesis using a lipophilicity based hypothesis to achieve the targeted rapid onset of action in combination with a long duration of action. The profiling of the two series led to identification of the α-substituted cyclopentyl analogue 2 as the optimal compound with a comparable profile to the inhaled once-daily long-acting β2-adrenoceptor agonist indacaterol. On the basis of these data 2 was promoted as the backup development candidate to indacaterol from the Novartis LABA project.