1-((4R)-2,2-dimethyl-[1,3]dioxolan-4-yl)-2-(4-(4-trifluoromethoxyphenoxy)phenylsulfonyl)ethanone | 286845-22-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-((4R)-2,2-dimethyl-[1,3]dioxolan-4-yl)-2-(4-(4-trifluoromethoxyphenoxy)phenylsulfonyl)ethanone
• 英文别名: 1-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-2-[4-[4-(trifluoromethoxy)phenoxy]phenyl]sulfonylethanone
• CAS: 286845-22-5
• 化学式: C₂₀H₁₉F₃O₇S
• 分子量: 460.428
• InChiKey: DKYZMEBEWCKIJX-GOSISDBHSA-N

物化性质

• 熔点：
  80-81 °C
• 沸点：
  537.1±50.0 °C(Predicted)
• 密度：
  1.363±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  31
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  96.5
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  1-((4R)-2,2-dimethyl-[1,3]dioxolan-4-yl)-2-(4-(4-trifluoromethoxyphenoxy)phenylsulfonyl)ethanone 在 sodium tetrahydroborate 、 甲基磺酰氯 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 1.75h， 生成 (4S)-2,2-dimethyl-4-((Z)-2-(4-(4-trifluoromethoxyphenoxy)phenylsulfonyl)ethenyl)-[1,3]dioxolane
  参考文献：
  名称：

  Phenoxyphenyl Sulfone N-Formylhydroxylamines (Retrohydroxamates) as Potent, Selective, Orally Bioavailable Matrix Metalloproteinase Inhibitors

  摘要：

  A novel series of sulfone N-formylhydroxylamines (retrohydroxamates) have been investigated as matrix metalloproteinases (MMP) inhibitors. The substitution of the ether linkage of ABT-770 (5) with a sulfone group 13a led to a substantial increase in activity against MMP-9 but was accompanied by a loss of selectivity for inhibition of MMP-2 and -9 over MMP-1 and diminished oral exposure. Replacement of the biphenyl P1' substituent with a phenoxyphenyl group provided compounds that are highly selective for inhibition of MMP-2 and -9 over MMP-1. Optimization of the substituent adjacent to the retrohydroxamate center in this series led to the clinical candidate ABT-518 (6), a highly potent, selective, orally bioavailable MMP inhibitor that has been shown to significantly inhibit tumor growth in animal cancer models.

  DOI：

  10.1021/jm0103920
• 作为产物：
  描述：

  对氟苯甲砜 在 正丁基锂 、 potassium carbonate 作用下， 以 四氢呋喃 、 吡啶 、 正己烷 为溶剂， 反应 22.0h， 生成 1-((4R)-2,2-dimethyl-[1,3]dioxolan-4-yl)-2-(4-(4-trifluoromethoxyphenoxy)phenylsulfonyl)ethanone
  参考文献：
  名称：

  Phenoxyphenyl Sulfone N-Formylhydroxylamines (Retrohydroxamates) as Potent, Selective, Orally Bioavailable Matrix Metalloproteinase Inhibitors

  摘要：

  A novel series of sulfone N-formylhydroxylamines (retrohydroxamates) have been investigated as matrix metalloproteinases (MMP) inhibitors. The substitution of the ether linkage of ABT-770 (5) with a sulfone group 13a led to a substantial increase in activity against MMP-9 but was accompanied by a loss of selectivity for inhibition of MMP-2 and -9 over MMP-1 and diminished oral exposure. Replacement of the biphenyl P1' substituent with a phenoxyphenyl group provided compounds that are highly selective for inhibition of MMP-2 and -9 over MMP-1. Optimization of the substituent adjacent to the retrohydroxamate center in this series led to the clinical candidate ABT-518 (6), a highly potent, selective, orally bioavailable MMP inhibitor that has been shown to significantly inhibit tumor growth in animal cancer models.

  DOI：

  10.1021/jm0103920

文献信息

• Process for the selective N-formylation of N-hydroxylamines
  申请人：——

  公开号：US20010031896A1

  公开（公告）日：2001-10-18

  The instant invention provides a process for the selective N-formylation of N-hydroxylamines.

  这项瞬时发明提供了一种选择性N-甲酰化N-羟胺的过程。
• Process for the preparation of matrix metalloproteinase inhibitors
  申请人：——

  公开号：US20020128496A1

  公开（公告）日：2002-09-12

  The present invention discloses a process for the synthesis of reverse hydroxamate matrix metalloproteinase (MMP) inhibitors.

  本发明公开了一种合成逆向羟肟酸酯基质金属蛋白酶（MMP）抑制剂的方法。
• The Development of a Large-Scale Synthesis of Matrix Metalloproteinase Inhibitor, ABT-518
  作者：Sou-Jen Chang、Dilinie Fernando、Michael Fickes、Ashok K. Gupta、David R. Hill、Todd McDermott、Shyamal Parekh、Zhenping Tian、Steven J. Wittenberger

  DOI：10.1021/op025525l

  日期：2002.5.1

  A process for the preparation of matrix metalloproteinase inhibitor ABT-518 has been developed. Significant improvements have been made to the first generation synthesis and are described here. The new process is very robust and efficient; multikilogram quantities of the title compound have been synthesized for clinical trials. ABT-518 was prepared by this six-step synthetic sequence in 51% overall yield with >99% ee.
• REVERSE HYDROXAMATE INHIBITORS OF MATRIX METALLOPROTEINASES
  申请人：ABBOTT LABORATORIES

  公开号：EP1147101B1

  公开（公告）日：2002-11-20
• US6350902B2
  申请人：——

  公开号：US6350902B2

  公开（公告）日：2002-02-26