4S-(4-benzyloxy-phenyl)-3S-(4-fluoro-phenyl)-1-[3-(4-fluoro-phenyl)-3S-hydroxy-propyl]-azetidin-2-one | 923570-24-5

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: 4S-(4-benzyloxy-phenyl)-3S-(4-fluoro-phenyl)-1-[3-(4-fluoro-phenyl)-3S-hydroxy-propyl]-azetidin-2-one
• 英文别名: (3R,4S)-3-(4-fluorophenyl)-1-[(3S)-3-(4-fluorophenyl)-3-hydroxypropyl]-4-(4-phenylmethoxyphenyl)azetidin-2-one
• CAS: 923570-24-5
• 化学式: C₃₁H₂₇F₂NO₃
• 分子量: 499.557
• InChiKey: IOBZQIXWPLWHOA-FRXPANAUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  37
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  49.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4S-(4-benzyloxy-phenyl)-3S-(4-fluoro-phenyl)-1-[3-(4-fluoro-phenyl)-3S-hydroxy-propyl]-azetidin-2-one 在 palladium on activated charcoal 氢气 作用下， 以90%的产率得到3S-(4-fluoro-phenyl)-1-[3-(4-fluoro-phenyl)-3S-hydroxy-propyl]-4S-(4-hydroxy-phenyl)-azetidin-2-one
  参考文献：
  名称：

  Ezetimibe analogs with a reorganized azetidinone ring: Design, synthesis, and evaluation of cholesterol absorption inhibitions

  摘要：

  The underlying principle of drug design in this paper is that the maximum retention of the functional groups that exist in the marketed drug would provide a higher probability for comparable safety while the conformational changes in the newly created analogs should not constitute a significant structural variation to adversely affect biological activity. Four individual isomers of backbone re-organized ezetimibe analogs were designed and synthesized. Their effects on the cholesterol levels in rat serum were evaluated by a high-cholesterol and high-fat diet feeding experiment. All the new analogs showed significant effect in lowering the levels of total cholesterol in serum. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.09.078
• 作为产物：
  描述：

  在 氢氧化钾 、 ammonium cerium(IV) nitrate 作用下， 以 四氢呋喃 、 二甲基亚砜 为溶剂， 生成 4S-(4-benzyloxy-phenyl)-3S-(4-fluoro-phenyl)-1-[3-(4-fluoro-phenyl)-3S-hydroxy-propyl]-azetidin-2-one
  参考文献：
  名称：

  Ezetimibe analogs with a reorganized azetidinone ring: Design, synthesis, and evaluation of cholesterol absorption inhibitions

  摘要：

  The underlying principle of drug design in this paper is that the maximum retention of the functional groups that exist in the marketed drug would provide a higher probability for comparable safety while the conformational changes in the newly created analogs should not constitute a significant structural variation to adversely affect biological activity. Four individual isomers of backbone re-organized ezetimibe analogs were designed and synthesized. Their effects on the cholesterol levels in rat serum were evaluated by a high-cholesterol and high-fat diet feeding experiment. All the new analogs showed significant effect in lowering the levels of total cholesterol in serum. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.09.078

文献信息

• Novel Substituted Azetidinones
  申请人：Pfefferkorn Jeffrey A.

  公开号：US20080227974A1

  公开（公告）日：2008-09-18

  Novel azetidinones and pharmaceutical compositions are described, as are the methods of using such compounds and compositions to treat subjects, including humans, suffering from hyperlipidemia, hypercholesterolemia, hypertriglyceridemia and atherosclerosis.

  本发明涉及一种新型的氮杂环丙酮类化合物及其药用组合物，以及使用此类化合物和组合物治疗高脂血症、高胆固醇血症、高甘油三酯血症和动脉粥样硬化等疾病的方法，包括治疗人类。
• [EN] NOVEL SUBSTITUTED AZETIDINONES<br/>[FR] NOUVEAUX AZETIDINONES SUBSTITUES
  申请人：WARNER LAMBERT CO

  公开号：WO2007015161A1

  公开（公告）日：2007-02-08

  [EN] Novel azetidinones and pharmaceutical compositions are described, as are the methods of using such compounds and compositions to treat subjects, including humans, suffering from hyperlipidemia, hypercholesterolemia, hypertriglyceridemia and atherosclerosis.
  [FR] La présente invention concerne de nouveaux azétidinones et de nouvelles composition pharmaceutiques, ainsi que des procédés d'utilisation de ces composés et de ces compositions pour traiter des sujets, notamment des hommes, souffrant d'hyperlipidémie, d'hypercholestérolémie, d'hypertriglycéridémie et d'athérosclérose.
• Ezetimibe analogs with a reorganized azetidinone ring: Design, synthesis, and evaluation of cholesterol absorption inhibitions
  作者：Xianxiu Xu、Renzhong Fu、Jin Chen、Shengwu Chen、Xu Bai

  DOI：10.1016/j.bmcl.2006.09.078

  日期：2007.1

  The underlying principle of drug design in this paper is that the maximum retention of the functional groups that exist in the marketed drug would provide a higher probability for comparable safety while the conformational changes in the newly created analogs should not constitute a significant structural variation to adversely affect biological activity. Four individual isomers of backbone re-organized ezetimibe analogs were designed and synthesized. Their effects on the cholesterol levels in rat serum were evaluated by a high-cholesterol and high-fat diet feeding experiment. All the new analogs showed significant effect in lowering the levels of total cholesterol in serum. (c) 2006 Elsevier Ltd. All rights reserved.