(4-{(2R,3R)-1-(4-fluoro-phenyl)-3-[(RS)-2-(4-fluoro-phenyl)-2-oxoethylsulfanyl]-4-oxo-azetidin-2-yl}-phenoxy)-acetic acid | 858104-50-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酰胺类
• 英文名称: (4-{(2R,3R)-1-(4-fluoro-phenyl)-3-[(RS)-2-(4-fluoro-phenyl)-2-oxoethylsulfanyl]-4-oxo-azetidin-2-yl}-phenoxy)-acetic acid
• 英文别名: [4-((2R,3R)-1-(4-fluorophenyl)-3-{[2-(4-fluorophenyl)-2-oxoethyl]thio}-4-oxoazetidin-2-yl)phenoxy]acetic acid；(3R,4R)-1-(4-fluorophenyl)-3-[(4-fluorobenzoyl)methylthio]-4-[4-(carboxymethoxy)phenyl]azetidin-2-one；2-[4-[(2R,3R)-1-(4-fluorophenyl)-3-[2-(4-fluorophenyl)-2-oxoethyl]sulfanyl-4-oxoazetidin-2-yl]phenoxy]acetic acid
• CAS: 858104-50-4
• 化学式: C₂₅H₁₉F₂NO₅S
• 分子量: 483.492
• InChiKey: QBRQXYWKXMZVJT-DNQXCXABSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  34
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  109
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (4-{(2R,3R)-1-(4-fluoro-phenyl)-3-[(RS)-2-(4-fluoro-phenyl)-2-oxoethylsulfanyl]-4-oxo-azetidin-2-yl}-phenoxy)-acetic acid 在 N-甲基吗啉 、 甲酸 作用下， 以 二氯甲烷 为溶剂， 反应 11.16h， 生成 tert-butyl (2-(4-((2R,3R)-1-(4-fluorophenyl)-3-((2-(4-fluorophenyl)-2-oxoethyl)thio)-4-oxoazetidin-2-yl)phenoxy)acetyl)-D-valyl-L-valinate
  参考文献：
  名称：

  [EN] DIPHENYLAZETIDINONE DERIVATES POSSESSING CHOLESTEROL ABSORPTION INHIBITORY ACTIVITY
  [FR] DERIVES DIPHENYLAZETIDINONE A ACTIVITE INHIBITRICE DE L'ABSORPTION DU CHOLESTEROL

  摘要：

  化合物的结构式（其中变量基团如定义所示）及其药学上可接受的盐、溶剂合物、该类盐的溶剂合物和它们的前药，以及它们作为治疗高脂血症的胆固醇吸收抑制剂的用途被描述。还描述了它们的制备方法和含有它们的药物组合物。

  公开号：

  WO2005061452A1
• 作为产物：
  描述：

  (4-甲酰基苯氧基)乙酸甲酯 在 titanium(IV) isopropylate 、 甲酸 、 N,O-双三甲硅基乙酰胺 、 四氯化钛 、 三乙胺 、 lithium chloride 作用下， 以 二氯甲烷 、 水 、 甲苯 、 乙腈 为溶剂， 反应 56.5h， 生成 (4-{(2R,3R)-1-(4-fluoro-phenyl)-3-[(RS)-2-(4-fluoro-phenyl)-2-oxoethylsulfanyl]-4-oxo-azetidin-2-yl}-phenoxy)-acetic acid
  参考文献：
  名称：

  Selection and Development of a Route for Cholesterol Absorption Inhibitor AZD4121

  摘要：

  The development of a synthetic route to the cholesterol absorption inhibitor AZD4121 is presented. Key steps are a highly enantioselective CBS reduction, a stereospecific Staudinger reaction, an amine/lithium chloride mediated ester hydrolysis, and a resolution of a 50:50 diastereomeric mixture by recrystallization. The synthesis was accomplished in 10 linear steps, and the overall yield, when compared with the lead optimization (LO) route, was improved from 1% to 20%. All purifications of intermediates through preparative HPLC or silica gel chromatography were avoided. This was possible since many of the intermediates along the route could be used as such in the next step until an intermediate with suitable crystalline properties could be identified and purified through crystallization.

  DOI：

  10.1021/op200314z

文献信息

• Diphenylazetidinone Derivatives Possessing Cholesterol Absorption Inhibitory Activity
  申请人：Alenfalk Susanne

  公开号：US20080064676A1

  公开（公告）日：2008-03-13

  Compounds of formula (I) (wherein variable groups are as defined within) pharmaceutically acceptable salts, solvates, solvates of such salts and prodrugs thereof and their use as cholesterol absorption inhibitors for the treatment of hyperlipidaemia are described. Processes for their manufacture and pharmaceutical compositions containing them are also described.

  本文描述了化学式(I)的化合物（其中变量基团如定义所示），其药学上可接受的盐、此类盐的溶剂化合物、其前药以及其作为治疗高脂血症的胆固醇吸收抑制剂的用途。本文还描述了其制造工艺和含有它们的制药组合物。
• Novel 2-Azetidinone Derivatives And Their Use As Cholesterol Absorption Inhibitors For The Treatment Of Hyperlipidaemia
  申请人：Alenfalk Susanne

  公开号：US20100216759A1

  公开（公告）日：2010-08-26

  Compounds of formula (I) (wherein variable groups are as defined within) pharmaceutically acceptable salts, solvates, solvates of such salts and prodrugs thereof and their use as cholesterol absorption inhibitors for the treatment of hyperlipidaemia are described. Processes for their manufacture and pharmaceutical compositions containing them are also described.

  本文描述了化学式(I)的化合物（其中变量基团如定义），其药学上可接受的盐、盐的溶剂、这种盐的溶剂和其前药，以及它们作为治疗高脂血症的胆固醇吸收抑制剂的用途。本文还描述了它们的制造过程和包含它们的制药组合物。
• 2-azetidinone derivatives and their use as cholesterol absorption inhibitors for the treatment of hyperlipidaemia
  申请人：AstraZeneca AB

  公开号：US07863265B2

  公开（公告）日：2011-01-04

  Compounds of formula (I) (wherein variable groups are as defined within) pharmaceutically acceptable salts, solvates, solvates of such salts and prodrugs thereof and their use as cholesterol absorption inhibitors for the treatment of hyperlipidaemia are described. Processes for their manufacture and pharmaceutical compositions containing them are also described.

  本文描述了化学式(I)的化合物（其中变量基团的定义如内部所述），其药学上可接受的盐，该盐的溶剂和其前药的溶剂以及它们作为治疗高脂血症的胆固醇吸收抑制剂的用途。还描述了制造它们的过程和含有它们的药物组合物。
• Diphenylazetidinone derivatives possessing cholesterol absorption inhibitory activity
  申请人：AstraZeneca AB

  公开号：US07871998B2

  公开（公告）日：2011-01-18

  Compounds of formula (I): (wherein variable groups are as defined within) pharmaceutically acceptable salts, solvates, solvates of such salts and prodrugs thereof and their use as cholesterol absorption inhibitors for the treatment of hyperlipidaemia are described. Processes for their manufacture and pharmaceutical compositions containing them are also described.

  本文描述了化学式（I）的化合物：（其中变量基团的定义如下）药学上可接受的盐，其溶剂化物，这些盐的溶剂化物及其前药，并将其用作胆固醇吸收抑制剂，用于治疗高脂血症。还描述了它们的制造过程和含有它们的制药组合物。
• 2-Azetidinone Derivatives For The Treatment Of Hyperlipidaemic Diseases
  申请人：Dahlstrom Mikael

  公开号：US20100152156A1

  公开（公告）日：2010-06-17

  The invention relates to novel 2-azetidinone derivatives of formula (I) and to pharmaceutically acceptable salts, solvates and prodrugs thereof. The compounds are cholesterol absorption inhibitors, useful in the treatment of hyperlipidaemic conditions. The invention also relates to processes for their manufacture and to pharmaceutical compositions containing them.

  本发明涉及公式（I）的新型2-氮杂环己酮衍生物，以及其药学上可接受的盐、溶剂合物和前药。这些化合物是胆固醇吸收抑制剂，可用于治疗高脂血症状况。本发明还涉及其制造的方法和含有它们的制药组合物。