5'-chloro-N-[(1S,2S)-1-(hydroxymethyl)-2-methylbutyl]thiophene-2'-sulfonamide | 443988-75-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩类
• 英文名称: 5'-chloro-N-[(1S,2S)-1-(hydroxymethyl)-2-methylbutyl]thiophene-2'-sulfonamide
• 英文别名: 5-chloro-N-[(1S,2S)-1-(hydroxymethyl)-2-methylbutyl]-2-thiophenesulfonamide；5-chloro-N-[(1S,2S)-1-(hydroxymethyl)-2-methylbutyl]thiophene-2-sulfonamide；5-Chlorothiophene-2-sulfonyl isoleucinol；5-chloro-N-[(2S,3S)-1-hydroxy-3-methylpentan-2-yl]thiophene-2-sulfonamide
• CAS: 443988-75-8
• 化学式: C₁₀H₁₆ClNO₃S₂
• 分子量: 297.827
• InChiKey: VAIPHPAXOJKZMG-JGVFFNPUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  17
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  103
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5'-chloro-N-[(1S,2S)-1-(hydroxymethyl)-2-methylbutyl]thiophene-2'-sulfonamide 在 氯磺酸 作用下， 以 乙酸乙酯 为溶剂， 反应 0.58h， 生成 (2S,3R)-2-{[(5-chloro-2-thienyl)sulfonyl]amino}-3-methylpentyl Hydrogen Sulfate
  参考文献：
  名称：

  COMPOSITIONS CONTAINING O-SULFATE AND O-PHOSPHATE CONTAINING ARYL SULFONAMIDE DERIVATIVES USEFUL AS beta-AMYLOID INHIBITORS

  摘要：

  提供一种具有I或II式结构或其药学上可接受的盐和/或水合物的合成化合物。其中，公式I和公式II定义如下：其中R1为取代芳基或取代杂环芳基；R2和R3分别选自CF3、取代苯基、C1-C4烷基、取代C1-C4烷基、(CF3)nC1-C4烷基、(CF3)n(取代C1-C4烷基)的群，但当R2或R3为CF3时，另一个不是未取代的烷基；R4和R4′分别选自M、C1-C4烷基、苯基和苄基的群，其中M是选择自钠、锂、钙、镁和钾的金属离子，或R4和R4′结合形成环状结构。还提供制备这种化合物的方法和其用途。

  公开号：

  US20090181932A1
• 作为产物：
  描述：

  5-氯噻唑-2-磺酰氯 、 L-异亮氨醇 在 三乙胺 作用下， 以 乙腈 为溶剂， 生成 5'-chloro-N-[(1S,2S)-1-(hydroxymethyl)-2-methylbutyl]thiophene-2'-sulfonamide
  参考文献：
  名称：

  Discovery of Begacestat, a Notch-1-Sparing γ-Secretase Inhibitor for the Treatment of Alzheimer’s Disease

  摘要：

  SAR on HTS hits I and 2 led to the potent, Notch-l-sparing GSI 9, which lowered brain A beta in Tg2576 mice at 100 mg/kg po. Converting the metabolically labile methyl groups in 9 to trifluoromethyl groups afforded the more stable analogue 10, which had improved in vivo potency. Further side chain modification afforded the potent Notch-1-sparing GSI begacestat (5). which was selected for development for the treatment of Alzheimer's disease.

  DOI：

  10.1021/jm801252w

文献信息

• Heterocyclic sulfonamide inhibitors of beta amyloid production
  申请人：ArQule

  公开号：US20020183361A1

  公开（公告）日：2002-12-05

  Compounds of Formula (I), 1 wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , T, W, X, Y and Z are as defined herein are provided, together with pharmaceutically acceptable salt, hydrates and/or prodrugs thereof. Methods of using these compounds for inhibiting beta amyloid production and for treatment of Alzheimer's Disease and Down's syndrome are described

  提供了符合以下定义的化合物（I）的化合物，其中R1、R2、R3、R4、R5、R6、T、W、X、Y和Z的定义如下，以及其药用盐、水合物和/或前药。描述了使用这些化合物抑制β淀粉样蛋白产生以及治疗阿尔茨海默病和唐氏综合征的方法。
• HETEROCYCLIC SULFONAMIDE INHIBITORS OF BETA AMYLOID PRODUCTION
  申请人：Kreft Anthony F.

  公开号：US20100022594A1

  公开（公告）日：2010-01-28

  Compounds of Formula (I), wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , T, W, X, Y and Z are as defined herein are provided, together with pharmaceutically acceptable salt, hydrates and/or prodrugs thereof. Methods of using these compounds for inhibiting beta amyloid production and for treatment of Alzheimer's disease and Down's syndrome are described.

  提供式(I)的化合物，其中R1、R2、R3、R4、R5、R6、T、W、X、Y和Z的定义如本文所述，以及其药学上可接受的盐、水合物和/或前药。描述了使用这些化合物抑制β淀粉样蛋白产生和治疗阿尔茨海默病和唐氏综合症的方法。
• Heterocyclic sulfonamide inhibitors of β amyloid production
  申请人：Wyeth

  公开号：US07691884B2

  公开（公告）日：2010-04-06

  Compounds of Formula (I), wherein R1, R2, R3, R4, R5, R6, T, W, X, Y and Z are as defined herein are provided, together with pharmaceutically acceptable salt, hydrates and/or prodrugs thereof. Methods of using these compounds for determining β-amyloid levels in a subject are described.

  本发明提供了化学式（I）的化合物，其中R1，R2，R3，R4，R5，R6，T，W，X，Y和Z的定义如本文所述，并提供其药学上可接受的盐，水合物和/或前药。还描述了使用这些化合物在受试者中确定β-淀粉样蛋白水平的方法。
• Heterocyclic Sulfonamide Inhibitors of Beta Amyloid Production
  申请人：Kreft Anthony F.

  公开号：US20110034513A1

  公开（公告）日：2011-02-10

  Compounds of Formula (I), wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , T, W, X, Y and Z are as defined herein are provided, together with pharmaceutically acceptable salt, hydrates and/or prodrugs thereof. Methods of using these compounds for inhibiting beta amyloid production and for treatment of Alzheimer's disease and Down's syndrome are described.

  提供式(I)的化合物，其中R1、R2、R3、R4、R5、R6、T、W、X、Y和Z的定义如本文所述，以及其药学上可接受的盐、水合物和/或前药。本文描述了使用这些化合物抑制β淀粉样蛋白生成和治疗阿尔茨海默病和唐氏综合症的方法。
• Discovery of Begacestat, a Notch-1-Sparing γ-Secretase Inhibitor for the Treatment of Alzheimer’s Disease
  作者：Scott C. Mayer、Anthony F. Kreft、Boyd Harrison、Magid Abou-Gharbia、Madelene Antane、Suzan Aschmies、Kevin Atchison、Michael Chlenov、Derek C. Cole、Thomas Comery、George Diamantidis、John Ellingboe、Kristi Fan、Rocco Galante、Cathleen Gonzales、Douglas M. Ho、Molly E. Hoke、Yun Hu、Donna Huryn、Uday Jain、Mei Jin、Kenneth Kremer、Dennis Kubrak、Melissa Lin、Peimin Lu、Ron Magolda、Robert Martone、William Moore、Aram Oganesian、Menelas N. Pangalos、Alex Porte、Peter Reinhart、Lynn Resnick、David R. Riddell、June Sonnenberg-Reines、Joseph R. Stock、Shaiu-Ching Sun、Erik Wagner、Ting Wang、Kevin Woller、Zheng Xu、Margaret M. Zaleska、Joseph Zeldis、Minsheng Zhang、Hua Zhou、J. Steven Jacobsen

  DOI：10.1021/jm801252w

  日期：2008.12.11

  SAR on HTS hits I and 2 led to the potent, Notch-l-sparing GSI 9, which lowered brain A beta in Tg2576 mice at 100 mg/kg po. Converting the metabolically labile methyl groups in 9 to trifluoromethyl groups afforded the more stable analogue 10, which had improved in vivo potency. Further side chain modification afforded the potent Notch-1-sparing GSI begacestat (5). which was selected for development for the treatment of Alzheimer's disease.