(2S,4S)-4-hydroxy-2-methyl-4-[2-(1-methyl-2-oxoindolin-5-ylthio)thien-4-yl]-tetrahydropyran | 406463-50-1

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: (2S,4S)-4-hydroxy-2-methyl-4-[2-(1-methyl-2-oxoindolin-5-ylthio)thien-4-yl]-tetrahydropyran
• 英文别名: 5-({4-[(2S,4S)-4-Hydroxy-2-methyloxan-4-yl]thiophen-2-yl}sulfanyl)-1-methyl-1,3-dihydro-2H-indol-2-one；5-[4-[(2S,4S)-4-hydroxy-2-methyloxan-4-yl]thiophen-2-yl]sulfanyl-1-methyl-3H-indol-2-one
• CAS: 406463-50-1
• 化学式: C₁₉H₂₁NO₃S₂
• 分子量: 375.513
• InChiKey: MQLADKMVHOOVET-BUXKBTBVSA-N

物化性质

• 沸点：
  665.6±55.0 °C(Predicted)
• 密度：
  1.38±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  103
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  pyridinium-S-(1-methyl-2-oxo-2,3-dihydro-1H-indol-5-yl)thiosulphate 在 potassium cyanide 、 硫酸 、 碘 、 sodium carbonate 、 三乙胺 作用下， 以 二氯甲烷 、 水 、 甲苯 、 乙腈 为溶剂， 反应 67.25h， 生成 (2S,4S)-4-hydroxy-2-methyl-4-[2-(1-methyl-2-oxoindolin-5-ylthio)thien-4-yl]-tetrahydropyran 、 5-[[4-[(2S,4R)-4-hydroxy-2-methyl-tetrahydropyran-4-yl]-2-thienyl]sulfanyl]-1-methyl-indolin-2-one
  参考文献：
  名称：

  Efficient Syntheses of AZD4407 via Thioether Formation by Nucleophilic Attack of Organometallic Species on Sulphur

  摘要：

  The development of two efficient strategies for the synthesis of AZD4407 is reported, both of which are considered suitable for large-scale manufacture. In the first approach, 3-bromothiophene is coupled with (2S)-2-methyltetrahydropyran-4one using Grignard chemistry. Following hydroxyl protection and lithiation at thiophene C-2, reaction with a protected 5-mercapto-1-methyl-1,3-dihydro-indol-2-one derivative bearing a leaving group on sulphur provides AZD4407 after acid-catalysed deprotection and epimerisation. The second approach starts from 2,4-dibromothiophene, which undergoes a selective Grignard exchange reaction at C-2 followed by reaction with similar protected mercapto-oxindole derivatives. Reprotection of the oxindole ring, followed by a second Grignard exchange, and reaction with (2S)-2-methyltetrahydropyran-4-one provides AZD4407 after acid-catalysed deprotection and epimerisation.

  DOI：

  10.1021/op0500483

文献信息

• TRICYCLIC INHIBITORS OF 5-LIPOXYGENASE
  申请人：Hutchinson John Howard

  公开号：US20070173508A1

  公开（公告）日：2007-07-26

  Described herein are compounds and pharmaceutical compositions containing such compounds, which inhibit the activity of 5-lipoxygenase (5-LO). Also described herein are methods of using such 5-LO inhibitors, alone and in combination with other compounds, for treating respiratory, cardiovascular, and other leukotriene-dependent or leukotriene mediated conditions, diseases, or disorders.

  本文描述了含有这些化合物的化合物和药物组合物，这些化合物抑制5-脂氧合酶（5-LO）的活性。本文还描述了使用这种5-LO抑制剂的方法，单独或与其他化合物结合，用于治疗呼吸系统、心血管系统和其他依赖或介导白三烯的状况、疾病或紊乱。
• Novel Use
  申请人：——

  公开号：US20020040047A1

  公开（公告）日：2002-04-04

  The invention relates to the use of 4-aryl-4-hydroxy-tetrahydropyrans and 3-aryl-3-hydroxy-tetrahydrofurans for the treatment or prevention of chronic obstructive pulmonary disease.

  这项发明涉及使用4-芳基-4-羟基-四氢吡喃和3-芳基-3-羟基-四氢呋喃来治疗或预防慢性阻塞性肺疾病。
• INDOLIZINE INHIBITORS OF 5-LIPOXYGENASE
  申请人：Roppe Jeffrey Roger

  公开号：US20120214840A1

  公开（公告）日：2012-08-23

  Described herein are compounds and pharmaceutical compositions containing such compounds, which inhibit the activity of 5-lipoxygenase (5-LO). Also described herein are methods of using such 5-LO inhibitors, alone and in combination with other compounds, for treating respiratory, cardiovascular, and other leukotriene-dependent or leukotriene mediated conditions, diseases, or disorders.

  本文所述的是含有这些化合物的药物组合物，这些化合物抑制5-脂氧化酶（5-LO）的活性。本文还描述了使用这种5-LO抑制剂的方法，单独或与其他化合物联合使用，用于治疗呼吸系统、心血管系统和其他依赖或介导白三烯的情况、疾病或障碍。
• US7919621B2
  申请人：——

  公开号：US7919621B2

  公开（公告）日：2011-04-05
• [EN] INDOLIZINE INHIBITORS OF 5-LIPOXYGENASE<br/>[FR] INHIBITEURS INDOLIZINE DE 5-LIPOXYGÉNASE
  申请人：AMIRA PHARMACEUTICALS INC

  公开号：WO2011038086A2

  公开（公告）日：2011-03-31

  Described herein are compounds and pharmaceutical compositions containing such compounds, which inhibit the activity of 5-lipoxygenase (5-LO). Also described herein are methods of using such 5-LO inhibitors, alone and in combination with other compounds, for treating respiratory, cardiovascular, and other leukotriene-dependent or leukotriene mediated conditions, diseases, or disorders.