3-碘-5-[甲基(甲基磺酰基)氨基]苯甲酸甲酯 | 847157-48-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 3-碘-5-[甲基(甲基磺酰基)氨基]苯甲酸甲酯
• 英文名称: methyl 3-iodo-5-[methyl(methylsulfonyl)amino]benzoate
• 英文别名: Methyl 3-iodo-5-[(methanesulfonyl)(methyl)amino]benzoate
• CAS: 847157-48-6
• 化学式: C₁₀H₁₂INO₄S
• 分子量: 369.18
• InChiKey: MLQYFGZOZAWEET-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  72.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-碘-5-[甲基(甲基磺酰基)氨基]苯甲酸甲酯 在 caesium carbonate sodium hydroxide 、 9-borabicyclo[3.3.1]nonane dimer 、 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 三苯胂 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 生成 3-(2-cyclopropylvinyl)-5-[methyl(methylsulfonyl)amino]benzoic acid
  参考文献：
  名称：

  Conformationally biased P3 amide replacements of β-secretase inhibitors

  摘要：

  We have synthesized and evaluated a series of conformationally biased P3 amide replacements based on an isophthalamide lead structure. The studies resulted in the identification of the beta-secretase inhibitor 7m which has an in vitro IC(50)=35 nM. The synthesis and biological activities of these compounds are described.

  DOI：

  10.1016/j.bmcl.2005.10.032
• 作为产物：
  描述：

  3-碘-5-硝基苯甲酸甲酯 在 吡啶 、 乙醇 、 tin chloride 、 sodium hydride 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 32.0h， 生成 3-碘-5-[甲基(甲基磺酰基)氨基]苯甲酸甲酯
  参考文献：
  名称：

  β-分泌酶的大环抑制剂：在动物模型中的功能活性。

  摘要：

  通过共价交联基于间苯二甲酰胺的抑制剂的P1和P3侧链来设计β-分泌酶的大环抑制剂。与最初的铅结构相比，大环化可显着提高效能和物理性能。更重要的是，当在鼠模型中给药时，这些大环抑制剂也表现出体内淀粉样蛋白降低。

  DOI：

  10.1021/jm060884i

文献信息

• [EN] 1,3,5-SUBSTITUTED PHENYL DERIVATIVE COMPOUNDS USEFUL AS BETA-SECRETASE INHIBITORS FOR THE TREATMENT OF ALZHEIMER'S DISEASE<br/>[FR] DERIVES DE PHENYLE 1,3,5-SUBSTITUES UTILES COMME INHIBITEURS DE LA BETA-SECRETASE POUR LE TRAITEMENT DE LA MALADIE D'ALZHEIMER
  申请人：MERCK & CO INC

  公开号：WO2005103020A1

  公开（公告）日：2005-11-03

  The present invention is directed to 1,3,5-phenyl substituted derivative compounds which are inhibitors of the beta-secretase enzyme and that are useful in the treatment of diseases in which the beta-secretase enzyme is involved, such as Alzheimer's disease. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the treatment of such diseases in which the beta-secretase enzyme is involved.

  本发明涉及1,3,5-苯基取代衍生物化合物，这些化合物是β-分泌酶的抑制剂，可用于治疗β-分泌酶参与的疾病，例如阿尔茨海默病。该发明还涉及包含这些化合物的药物组合物，以及这些化合物和组合物在治疗β-分泌酶参与疾病中的用途。
• [EN] PYRROLIDIN-3-YL COMPOUNDS USEFUL AS BETA-SECRETASE INHIBITORS FOR THE TREATMENT OF ALZHEIMER'S DISEASE<br/>[FR] COMPOSES PYRROLIDIN-3-YLE UTILES EN TANT QU'INHIBITEURS DE LA BETA-SECRETASE POUR LE TRAITEMENT DE LA MALADIE D'ALZHEIMER
  申请人：MERCK & CO INC

  公开号：WO2006002004A1

  公开（公告）日：2006-01-05

  The present invention is directed to pyrrolidin-3-yl derivative compounds which are inhibitors of the beta-secretase enzyme and that are useful in the treatment of diseases in which the beta-secretase enzyme is involved, such as Alzheimer's disease. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the treatment of such diseases in which the beta-secretase enzyme is involved.

  本发明涉及吡咯烷-3-基衍生物化合物，这些化合物是β-分泌酶的抑制剂，并且在治疗涉及β-分泌酶的疾病，如阿尔茨海默病中有用。该发明还涉及包含这些化合物的药物组合物，以及在治疗涉及β-分泌酶的这类疾病中使用这些化合物和组合物。
• [EN] BENZYLETHER AND BENZYLAMINO BETA-SECRETASE INHIBITORS FOR THE TREATMENT OF ALZHEIMER'S DISEASE<br/>[FR] INHIBITEURS DE BENZYLETHER ET BENZYLAMINO DE BETA-SECRETASE POUR TRAITER LA MALADIE D'ALZHEIMER
  申请人：MERCK & CO INC

  公开号：WO2005051914A1

  公开（公告）日：2005-06-09

  The present invention is directed to benzylether and benzylamino derivative compounds which are inhibitors of the beta-secretase enzyme and that are useful in the treatment of diseases in which the beta-secretase enzyme is involved, such as Alzheimer's disease. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the treatment of such diseases in which the beta-secretase enzyme is involved.

  本发明涉及苯乙醚和苄胺衍生物化合物，这些化合物是β-分泌酶的抑制剂，并且在治疗涉及β-分泌酶的疾病，如阿尔茨海默病中有用。该发明还涉及包含这些化合物的药物组合物，以及在治疗涉及β-分泌酶的这类疾病中使用这些化合物和组合物。
• [EN] MACROCYCLIC BETA-SECRETASE INHIBITORS FOR THE TREATMENT OF ALZHEIMER'S DISEASE<br/>[FR] INHIBITEURS MACROCYCLIQUES DE LA BETA-SECRETASE DESTINES AU TRAITEMENT DE LA MALADIE D'ALZHEIMER
  申请人：MERCK & CO INC

  公开号：WO2005018545A3

  公开（公告）日：2005-05-19
• Macrocyclic Inhibitors of β-Secretase:  Functional Activity in an Animal Model
  作者：Shawn J. Stachel、Craig A. Coburn、Sethu Sankaranarayanan、Eric A. Price、Beth L. Pietrak、Qian Huang、Janet Lineberger、Amy S. Espeseth、Lixia Jin、Joan Ellis、M. Katharine Holloway、Sanjeev Munshi、Timothy Allison、Daria Hazuda、Adam J. Simon、Samuel L. Graham、Joseph P. Vacca

  DOI：10.1021/jm060884i

  日期：2006.10.1

  A macrocyclic inhibitor of beta-secretase was designed by covalently cross-linking the P1 and P3 side chains of an isophthalamide-based inhibitor. Macrocyclization resulted in significantly improved potency and physical properties when compared to the initial lead structures. More importantly, these macrocyclic inhibitors also displayed in vivo amyloid lowering when dosed in a murine model.

  通过共价交联基于间苯二甲酰胺的抑制剂的P1和P3侧链来设计β-分泌酶的大环抑制剂。与最初的铅结构相比，大环化可显着提高效能和物理性能。更重要的是，当在鼠模型中给药时，这些大环抑制剂也表现出体内淀粉样蛋白降低。