3(R)-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4(S)-(4-hydroxyphenyl)-1-(4-iodophenyl)-2-azetidinone | 437713-52-5

• 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: 3(R)-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4(S)-(4-hydroxyphenyl)-1-(4-iodophenyl)-2-azetidinone
• 英文别名: SCH604813；(3R,4S)-3-[(3S)-3-(4-fluorophenyl)-3-hydroxypropyl]-4-(4-hydroxyphenyl)-1-(4-iodophenyl)azetidin-2-one；(3R,4S)-3-[(3S)3-(4-fluorophenyl)-3-hydroxypropyl]-4-(4-hydroxyphenyl)-1-(4-iodophenyl)azetidin-2-one
• CAS: 437713-52-5
• 化学式: C₂₄H₂₁FINO₃
• 分子量: 517.339
• InChiKey: MCJRNYRTLMDPFK-XPWALMASSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  60.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-(2-丙炔基)-甲烷磺酰胺 、 3(R)-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4(S)-(4-hydroxyphenyl)-1-(4-iodophenyl)-2-azetidinone 在 copper(I) iodide 、 三苯基膦钯 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 N-(3-{4-[(2S,3R)-3-[(3S)-3-(4-fluorophenyl)-3-hydroxypropyl]-2-(4-hydroxyphenyl)-4-oxoazetidin-1-yl]phenyl}prop-2-yn-1-yl)methanesulfonamide
  参考文献：
  名称：

  NPC1L1 (NPC3) and methods of identifying ligands thereof

  摘要：

  本发明提供了人类、大鼠和小鼠NPCIL1多肽以及编码该多肽的多核苷酸。提供了检测结合到NPC1L1并阻断肠道胆固醇吸收的配体的方法。还包括一种利用从毛细血管膜制备物中得到的膜来识别结合到NPCILI的配体的方法。结合到NPCILI的化合物可用于抑制受试者的肠道胆固醇吸收。

  公开号：

  US07901893B2
• 作为产物：
  描述：

  (1S)-1-(4-fluorophenyl)-3-[(2S,3R)-2-(4-hydroxyphenyl)-1-(4-iodophenyl)-4-oxoazetidin-3-yl]propyl acetate 在 lithium hydroxide 作用下， 以 四氢呋喃 为溶剂， 以56%的产率得到3(R)-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4(S)-(4-hydroxyphenyl)-1-(4-iodophenyl)-2-azetidinone
  参考文献：
  名称：

  Synthesis of iodinated biochemical tools related to the 2-azetidinone class of cholesterol absorption inhibitors

  摘要：

  The discoveries of Sch 48461 and Sch 58235 and their novel pharmacology of inhibition of cholesterol absorption have prompted efforts to determine their biological mechanism of action (MOA). To this end, a series of radioiodinated analogues with good to excellent in vivo activity have been designed and synthesized as single enantiomers. They are structurally consistent with the allowable SAR of the 2-azetidinone class of cholesterol absorption inhibitors. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(01)00750-8

文献信息

• Anti-hypercholesterolemic compounds
  申请人：DeVita J. Robert

  公开号：US20070078098A1

  公开（公告）日：2007-04-05

  This invention provides cholesterol absorption inhibitors of Formula I: and the pharmaceutically acceptable salts and esters thereof. The compounds are useful for lowering plasma cholesterol levels, particularly LDL cholesterol, and for treating and preventing atherosclerosis and atherosclerotic disease events.

  这项发明提供了化学式I的胆固醇吸收抑制剂及其药用盐和酯。这些化合物对降低血浆胆固醇水平，特别是LDL胆固醇，以及治疗和预防动脉粥样硬化和动脉粥样硬化疾病事件具有用处。
• Npcil1 (Npc3) And Methods Of Identifying Ligands Thereof
  申请人：Garcia-Calvo Maria Margarita

  公开号：US20100009461A1

  公开（公告）日：2010-01-14

  The present invention provides human, rat and mouse NPCIL1 polypeptides and polynucleotides encoding the polypeptides. Methods for detecting ligands which bind to NPC1L1 and block intestinal cholesterol absorption are provided. Also included is a method of identifying ligands which bind to NPCILI using membranes derived from brush border membrane preparations. Compounds that bind to NPCILI can be used for inhibiting intestinal cholesterol absorption in a subject.

  本发明提供人、大鼠和小鼠NPCIL1多肽和编码该多肽的多核苷酸。提供检测与NPC1L1结合并阻止肠道胆固醇吸收的配体的方法。还包括使用来自刷状缘膜制备的膜鉴定与NPCILI结合的配体的方法。与NPCILI结合的化合物可用于抑制受试者的肠道胆固醇吸收。
• ANTI-HYPERCHOLESTEROLEMIC COMPOUNDS
  申请人：DeVita Robert J.

  公开号：US20100035857A1

  公开（公告）日：2010-02-11

  This invention provides cholesterol absorption inhibitors of Formula I:I and the pharmaceutically acceptable salts thereof. The compounds are useful for lowering plasma cholesterol levels, particularly LDL cholesterol, and for treating and preventing atherosclerosis and atherosclerotic disease events.

  本发明提供了I式的胆固醇吸收抑制剂及其药学上可接受的盐。这些化合物可用于降低血浆胆固醇水平，特别是低密度脂蛋白胆固醇，并用于治疗和预防动脉粥样硬化和动脉粥样硬化性疾病事件。
• HETEROCYCLYL-SUBSTITUTED ANTI-HYPERCHOLESTEROLEMIC COMPOUNDS
  申请人：Morriello Gregori J.

  公开号：US20100069347A1

  公开（公告）日：2010-03-18

  This invention provides cholesterol absorption inhibitors of Formula I: and the pharmaceutically acceptable salts thereof, wherein R 12 is a hydroxylated alkyl group and R 9 contains a heterocyclic ring. The compounds are useful for lowering plasma cholesterol levels, particularly LDL cholesterol, and for treating atherosclerosis and preventing atherosclerotic disease events.

  本发明提供了I式胆固醇吸收抑制剂及其药学上可接受的盐，其中R12是一个羟基化的烷基基团，而R9包含一个杂环环。这些化合物对降低血浆胆固醇水平，特别是低密度脂蛋白胆固醇，以及治疗动脉粥样硬化和预防动脉粥样硬化疾病事件具有用处。
• Anti-Hypercholesterolemic Compounds
  申请人：DeVita Robert J.

  公开号：US20090137546A1

  公开（公告）日：2009-05-28

  This invention provides cholesterol absorption inhibitors of Formula I: and the pharmaceutically acceptable salts and esters thereof. The compounds are useful for lowering plasma cholesterol levels, particularly LDL cholesterol, and for treating and preventing atherosclerosis and atherosclerotic disease events.

  该发明提供了公式I的胆固醇吸收抑制剂，以及其药学上可接受的盐和酯。这些化合物可用于降低血浆胆固醇水平，尤其是LDL胆固醇，并用于治疗和预防动脉硬化和动脉粥样硬化疾病事件。