7-{4-[(6-bromohexyl)oxy]butyl}thiochromane 1,1-dioxide | 855997-38-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 硫铬烷
• 英文名称: 7-{4-[(6-bromohexyl)oxy]butyl}thiochromane 1,1-dioxide
• 英文别名: 7-[4-(6-bromohexoxy)butyl]-3,4-dihydro-2H-thiochromene 1,1-dioxide
• CAS: 855997-38-5
• 化学式: C₁₉H₂₉BrO₃S
• 分子量: 417.407
• InChiKey: UMYQSMGYIJELGK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  24
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  51.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  维兰特罗杂质4 、 7-{4-[(6-bromohexyl)oxy]butyl}thiochromane 1,1-dioxide 在 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 DMF (N,N-dimethyl-formamide) 为溶剂， 反应 17.0h， 生成 (1R)-1-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-2-({6-[4-(1,1-dioxido-3,4-dihydro-2H-thiochromen-7-yl)butoxy]hexyl}amino)ethanol
  参考文献：
  名称：

  [EN] BENZOTHIOPHENE-AND BENZOTHIOCHROMENE-COMPRISING DERIVATIVES OF PHENETHANOLAMINE FOR THE TREATMENT
  [FR] BENZOTHIOPHENE- ET BENZOTHIOCHROMENE- COMPRENANT DES DERIVES DE PHENETHANOLAMINE POUR TRAITEMENTS

  摘要：

  公式（I）的化合物和其盐，溶剂合物以及生理学功能衍生物，可用于预防或治疗需要选择性β2-肾上腺素受体激动剂的临床病症，例如哮喘或慢性阻塞性肺疾病（COPD）。

  公开号：

  WO2005058867A1
• 作为产物：
  描述：

  7-溴硫代苯并二氢吡喃-4-酮 在 三乙基硅烷 、 9-硼双环[3.3.1]壬烷 、 间氯过氧苯甲酸 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 24.0h， 生成 7-{4-[(6-bromohexyl)oxy]butyl}thiochromane 1,1-dioxide
  参考文献：
  名称：

  Discovery of a Rapidly Metabolized, Long-Acting β₂ Adrenergic Receptor Agonist with a Short Onset Time Incorporating a Sulfone Group Suitable for Once-Daily Dosing

  摘要：

  A series of novel, potent, and selective human beta(2) adrenoceptor agonists incorporating a sulfone moiety on the terminal right-hand-side phenyl ring of (R)-salmeterol is presented. Sulfone 10b had salmeterol-like potency and selectivity profile, long duration of action on guinea pig trachea, and longer than salmeterol duration of action in vivo, suitable for once-daily dosing. It had lower than salmeterol oral absorption in rat, lower bioavailability in rat and dog, and a high turnover in human hepatocytes. It was metabolized in human hepatocytes by hydroxylation, oxidation, cleavage, and conjugation; most of the metabolites would be expected to have reduced or no beta(2) activity. The 4-biphenylsulfonic acid was identified as a crystalline, non-hygroscopic salt of 10b, suitable for inhaled delivery. Furthermore, it was free of any genetic toxicity issues and was considered as a backup to vilanterol.

  DOI：

  10.1021/jm401532g

文献信息

• [EN] BENZOTHIOPHENE-AND BENZOTHIOCHROMENE-COMPRISING DERIVATIVES OF PHENETHANOLAMINE FOR THE TREATMENT<br/>[FR] BENZOTHIOPHENE- ET BENZOTHIOCHROMENE- COMPRENANT DES DERIVES DE PHENETHANOLAMINE POUR TRAITEMENTS
  申请人：GLAXO GROUP LTD

  公开号：WO2005058867A1

  公开（公告）日：2005-06-30

  Compounds of formula (I) and salts, solvates, and physiologically functional derivatives thereof, useful for the prophylaxis or treatment of a clinical condition for which a selective β2-adrenoreceptor agonist is indicated, for example asthma or chronic obstructive pulmonary disease (COPD).

  公式（I）的化合物和其盐，溶剂合物以及生理学功能衍生物，可用于预防或治疗需要选择性β2-肾上腺素受体激动剂的临床病症，例如哮喘或慢性阻塞性肺疾病（COPD）。
• [EN] METHODS OF TREATMENT WITH LXR AGONISTS<br/>[FR] METHODES DE TRAITEMENT UTILISANT DES AGONISTES DU LXR
  申请人：SMITHKLINE BEECHAM CORP

  公开号：WO2005055998A1

  公开（公告）日：2005-06-23

  The present invention relates generally to the use of LXR agonists in the prevention and/or treatment of eosinophilia or IL-13 overproduction, or diseases arising from eosinophilia or IL-13 production, such as allergy or asthma.

  本发明通常涉及使用LXR激动剂预防和/或治疗嗜酸性粒细胞增多或IL-13过度产生，或由嗜酸性粒细胞增多或IL-13产生引起的疾病，如过敏或哮喘。
• Benzothiophen and thiochrone containing phenethanolamine derivatives for the treatment of respiratory disorders
  申请人：Biggadike Keith

  公开号：US20070172385A1

  公开（公告）日：2007-07-26

  Compounds of formula (I): and salts, solvates, and physiologically functional derivatives thereof, useful for the prophylaxis or treatment of a clinical condition for which a selective β 2 -adrenoreceptor agonist is indicated, for example asthma or chronic obstructive pulmonary disease (COPD).

  公式(I)的化合物及其盐、溶剂合物和生理功能衍生物，可用于预防或治疗选择性β2-肾上腺素能受体激动剂适用的临床疾病，例如哮喘或慢性阻塞性肺疾病（COPD）。
• US7294650B2
  申请人：——

  公开号：US7294650B2

  公开（公告）日：2007-11-13
• Discovery of a Rapidly Metabolized, Long-Acting β₂ Adrenergic Receptor Agonist with a Short Onset Time Incorporating a Sulfone Group Suitable for Once-Daily Dosing
  作者：Panayiotis A. Procopiou、Victoria J. Barrett、Keith Biggadike、Peter R. Butchers、Andrew Craven、Alison J. Ford、Stephen B. Guntrip、Duncan S. Holmes、Sara C. Hughes、Anne E. Jones、Brian E. Looker、Peter J. Mutch、Mark Ruston、Deborah Needham、Claire E. Smith

  DOI：10.1021/jm401532g

  日期：2014.1.9

  A series of novel, potent, and selective human beta(2) adrenoceptor agonists incorporating a sulfone moiety on the terminal right-hand-side phenyl ring of (R)-salmeterol is presented. Sulfone 10b had salmeterol-like potency and selectivity profile, long duration of action on guinea pig trachea, and longer than salmeterol duration of action in vivo, suitable for once-daily dosing. It had lower than salmeterol oral absorption in rat, lower bioavailability in rat and dog, and a high turnover in human hepatocytes. It was metabolized in human hepatocytes by hydroxylation, oxidation, cleavage, and conjugation; most of the metabolites would be expected to have reduced or no beta(2) activity. The 4-biphenylsulfonic acid was identified as a crystalline, non-hygroscopic salt of 10b, suitable for inhaled delivery. Furthermore, it was free of any genetic toxicity issues and was considered as a backup to vilanterol.