(5R)-3-[6-(3-butyn-1-yloxy)-hexyl]-5-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-1,3-oxazolidin-2-one | 452339-74-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并二恶烷
• 英文名称: (5R)-3-[6-(3-butyn-1-yloxy)-hexyl]-5-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-1,3-oxazolidin-2-one
• 英文别名: (5R)-3-[6-(but-3-ynyloxy)hexyl]-5-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-1,3-oxazolidin-2-one；(5R)-3-[6-(But-3-ynyloxy)hexyl]5-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-1,3-oxazolidin-2-one；(5R)-3-(6-but-3-ynoxyhexyl)-5-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-1,3-oxazolidin-2-one
• CAS: 452339-74-1
• 化学式: C₂₃H₃₁NO₅
• 分子量: 401.503
• InChiKey: KLIXFVNGNBMHJW-NRFANRHFSA-N

物化性质

• 沸点：
  587.7±50.0 °C(Predicted)
• 密度：
  1.119±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  29
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  57.2
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (5R)-3-[6-(3-butyn-1-yloxy)-hexyl]-5-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-1,3-oxazolidin-2-one 在 platinum(IV) oxide 、 bis-triphenylphosphine-palladium(II) chloride 、 potassium trimethylsilonate 、 氢气 、 溶剂黄146 、 三乙胺 、 copper(l) chloride 作用下， 以 四氢呋喃 、 乙醇 、 水 、 乙腈 为溶剂， 反应 6.5h， 生成 4-((1R)-2-{[6-({4-[3-(cyclopentylsulfonyl)phenyl]butyl}oxy)-hexyl]amino}-1-hydroxyethyl)-2-(hydroxymethyl)phenol
  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
• 作为产物：
  描述：

  1-bromo-6-(but-3-ynyloxy)hexane 、 (5R)-5-(2,2-二甲基-4H-1,3-苯并二氧杂环己-6-基)-1,3-恶唑烷-2-酮 在 sodium hydride 作用下， 以 DMF (N,N-dimethyl-formamide) 为溶剂， 反应 3.02h， 生成 (5R)-3-[6-(3-butyn-1-yloxy)-hexyl]-5-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-1,3-oxazolidin-2-one
  参考文献：
  名称：

  [EN] PHENETHANOLAMINE DERIVATIVES FOR TREATMENT OF RESPIRATORY DISEASES
  [FR] DERIVES DE PHENETHANOLAMINE POUR TRAITER DES MALADIES RESPIRATOIRES

  摘要：

  本发明涉及式（I）的新化合物，涉及其制备方法，含有它们的药物组合物，以及它们在治疗中的应用，特别是在预防和治疗呼吸道疾病中的应用。

  公开号：

  WO2003072539A1

文献信息

• [EN] PHENETHANOLAMINE DERIVATIVES FOR THE TREATMENT OF RESPIRATORY DISEASES<br/>[FR] DERIVES DE PHENETHANOLAMINE PERMETTANT DE TRAITER DES MALADIES DES VOIES RESPIRATOIRES
  申请人：GLAXO GROUP LTD

  公开号：WO2004039762A1

  公开（公告）日：2004-05-13

  The present invention relates to novel compounds of formula (I), to a process for their manufacture, to pharmaceutical compositions containing them, and to their use in therapy, in particular their use in the prophylaxis and treatment of respiratory diseases.

  本发明涉及式（I）的新化合物，以及制备它们的方法，含有它们的药物组合物，以及它们在治疗中的应用，特别是在预防和治疗呼吸道疾病中的应用。
• [EN] PHENETHANOLAMINE DERIVATIVE FOR THE TREATMENT OF RESPIRATORY DISEASES<br/>[FR] DERIVE DE PHENETHANOLAMINE UTILISE DANS LE TRAITEMENT DE MALADIES RESPIRATOIRES
  申请人：GLAXO GROUP LTD

  公开号：WO2004037773A1

  公开（公告）日：2004-05-06

  The present invention relates to novel compounds of formula (I), to a process for their manufacture, to pharmaceutical compositions containing them, and to their use in therapy, in particular their use in the prophylaxis and treatment of respiratory diseases.

  本发明涉及公式（I）的新化合物，以及其制备方法、含有它们的药物组合物，以及它们在治疗中的使用，特别是在预防和治疗呼吸道疾病中的使用。
• [EN] PHENETHANOLAMINE DERIVATIVES FOR TREATMENT OF RESPIRATORY DISEASES<br/>[FR] DERIVES DE PHENETHANOLAMINE DESTINES AU TRAITEMENT DE MALADIES RESPIRATOIRES
  申请人：GLAXO GROUP LTD

  公开号：WO2005058299A1

  公开（公告）日：2005-06-30

  Compounds of formula (I): Wherein: R1 is-XSO2NR6R7; wherein X is -(CH2)p - or C2-6 alkenylene; p is an integer from 0 to 6; Ar2 is a mono or bicyclic heteroaryl or a bicyclic aryl group; 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：其中：R1是-XSO2NR6R7；其中X是-(CH2)p-或C2-6烯烃基；p是从0到6的整数；Ar2是单环或双环杂芳基或双环芳基基团；以及其盐类、溶剂合物和生理功能衍生物，用于预防或治疗选择性β2-肾上腺素受体激动剂适应症的临床病症，例如哮喘或慢性阻塞性肺病（COPD）。
• Agonists of beta-adrenoceptors
  申请人：——

  公开号：US20040242890A1

  公开（公告）日：2004-12-02

  The present invention relates to novel compounds of formula (I), to a process for their manufacture, to pharmaceutical compositions containing them, and to their use in therapy, in particular their use in the prophylaxis and treatment of respiratory diseases. 1

  本发明涉及公式(I)的新化合物，其制造方法，包含它们的制药组合物以及它们在治疗中的应用，特别是在呼吸系统疾病的预防和治疗中的应用。
• Novel anti-inflammatory 17.alpha.-heterocyclic-esters of 17.beta.carbothioate androstane derivatives
  申请人：——

  公开号：US20040248867A1

  公开（公告）日：2004-12-09

  There are provided compounds of formula (I) wherein R 1 represents C 1-6 alkyl or C 1-6 haloalkyl; R 2 represents a 4-7 membered non-aromatic ring containing 1-3 heteroatoms selected from O, N and S optionally substituted with one or more methyl, ethyl or halogen groups; R 3 represents hydrogen, methyl (which may be in either the &agr; or &bgr; configuration) or methylene; R 4 and R 5 are the same or different and each represents hydrogen or halogen; and (a) represents a single or a double bond; and salts and solvates thereof; processes for preparing them and their use in therapy. 1

  提供了式（I）的化合物，其中R1代表C1-6烷基或C1-6卤代烷基；R2代表一个含有1-3个异原子（选自O、N和S）的4-7成员非芳香环，可选地被一个或多个甲基、乙基或卤素基取代；R3代表氢、甲基（可以处于α或β构型）或亚甲基；R4和R5相同或不同，每个代表氢或卤素；而（a）代表单键或双键；以及它们的盐和溶剂化物；制备它们的过程以及它们在治疗中的用途。