(1S)-N-([4-(4-fluorophenyl)-2-oxo-2H-chromen-7-yl]methyl)-5-[1-hydroxy-1-(trifluoromethyl)propyl]-1,3,4-oxadiazol-2-aminium4-methylbenzenesulfonate | 1137737-87-1

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 新黄酮类化合物
• 英文名称: (1S)-N-([4-(4-fluorophenyl)-2-oxo-2H-chromen-7-yl]methyl)-5-[1-hydroxy-1-(trifluoromethyl)propyl]-1,3,4-oxadiazol-2-aminium4-methylbenzenesulfonate
• 英文别名: MK-0633 p-toluenesulfonate；MK-0633 tosylate；(S)-4-(4-fluorophenyl)-7-[({5-[1-hydroxy-1-(trifluoromethyl)propyl]-1,3,4-oxadiazol-2-yl}amino)-methyl]-2H-chromen-2-one p-toluenesulfonate；Setileuton tosylate；4-(4-fluorophenyl)-7-[[[5-[(2S)-1,1,1-trifluoro-2-hydroxybutan-2-yl]-1,3,4-oxadiazol-2-yl]amino]methyl]chromen-2-one;4-methylbenzenesulfonic acid
• CAS: 1137737-87-1
• 化学式: C₇H₈O₃S*C₂₂H₁₇F₄N₃O₄
• 分子量: 635.593
• InChiKey: NDAZWYKPMVDGGE-BOXHHOBZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.0
• 重原子数：
  44
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  160
• 氢给体数：
  3
• 氢受体数：
  14

反应信息

• 作为产物：
  描述：

  4-(4-氟苯基)-7-[[[5-[(1S)-1-羟基-1-(三氟甲基)丙基]-1,3,4-恶二唑-2-基]氨基]甲基]-2H-1-苯并吡喃-2-酮 、 对甲苯磺酸 以 甲醇 、 乙腈 为溶剂， 生成 (1S)-N-([4-(4-fluorophenyl)-2-oxo-2H-chromen-7-yl]methyl)-5-[1-hydroxy-1-(trifluoromethyl)propyl]-1,3,4-oxadiazol-2-aminium4-methylbenzenesulfonate
  参考文献：
  名称：

  Compounds and methods for leukotriene biosynthesis inhibition

  摘要：

  该发明提供了（-）4-（4-氟苯基）-7-[（{5-[1-羟基-1-（三氟甲基）丙基]-1,3,4-噻二唑-2-基}氨基）甲基]-2H-香豆素及其盐和晶体形式。这些化合物是5-LO抑制剂，可用于治疗哮喘、过敏性鼻炎、COPD和动脉硬化等疾病。

  公开号：

  US20090088477A1

文献信息

• Compounds and methods for leukotriene biosynthesis inhibition
  申请人：Gosselin Francis

  公开号：US20090088477A1

  公开（公告）日：2009-04-02

  This invention provides novel salt and crystalline forms thereof of (−)4-(4-fluorophenyl)-7-[(5-[1-hydroxy-1-(trifluoromethyl)propyl]-1,3,4-oxadiazol-2-yl}amino)-methyl]-2H-chromen-2-one. The compounds are 5-LO inhibitors and are useful for treatment of conditions such as asthma, allergic rhinitis, COPD, and atherosclerosis.

  该发明提供了（-）4-（4-氟苯基）-7-[（5-[1-羟基-1-（三氟甲基）丙基]-1,3,4-噻二唑-2-基}氨基）甲基]-2H-香豆素及其盐和晶体形式。这些化合物是5-LO抑制剂，可用于治疗哮喘、过敏性鼻炎、COPD和动脉硬化等疾病。
• CHROMENONE DERIVATIVES AND THEIR USE FOR LEUKOTRIENE BIOSYNTHESIS INHIBITION
  申请人：Merck Sharp & Dohme Corp.

  公开号：EP2203446A1

  公开（公告）日：2010-07-07
• US7915298B2
  申请人：——

  公开号：US7915298B2

  公开（公告）日：2011-03-29
• [EN] CHROMENONE DERIVATIVES AND THEIR USE FOR LEUKOTRIENE BIOSYNTHESIS INHIBITION<br/>[FR] DÉRIVÉS DE CHROMÉNONE ET LEUR UTILISATION POUR L'INHIBITION DE LA BIOSYNTHÈSE DES LEUCOTRIÈNES
  申请人：MERCK & CO INC

  公开号：WO2009042098A1

  公开（公告）日：2009-04-02

  This invention provides novel salt and crystalline forms thereof of (-) 4-(4-fluorophenyl)-7-[(5-[1-hydroxy-1-(trifluoromethyl)propyl]-1,3,4-oxadiazol-2-yl}-amino)-methyl]-2H-chromen-2-one. The compounds are 5-LO inhibitors and are useful for treatment of conditions such as asthma, allergic rhinitis, COPD, and atherosclerosis.
• A Practical Synthesis of 5-Lipoxygenase Inhibitor MK-0633
  作者：Francis Gosselin、Robert A. Britton、Ian W. Davies、Sarah J. Dolman、Danny Gauvreau、R. Scott Hoerrner、Gregory Hughes、Jacob Janey、Stephen Lau、Carmela Molinaro、Christian Nadeau、Paul D. O’Shea、Michael Palucki、Rick Sidler

  DOI：10.1021/jo100561u

  日期：2010.6.18

  Practical, chromatography-free syntheses of 5-lipoxygenase inhibitor MK-0633 p-toluenesullonate (1) are described. The first route used an asymmetric zincate addition to ethyl 2,2,2-trifluoropyruvate followed by 1,3,4-oxadiazole formation and reductive amination as key steps. An improved second route features an inexpensive diastereomeric salt resolution of vinyl hydroxy-acid 22 followed by a robust end-game featuring a through-process hydrazide acylation/1,3,4-oxadiazole ring closure/salt formation sequence to afford MK-0633 p-toluenesulfonate (1).