benzyl N-[(2S)-1-[4-(6-methylpyridin-2-yl)piperazin-1-yl]-1-oxo-6-(prop-2-enoylamino)hexan-2-yl]carbamate | 1400654-87-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: benzyl N-[(2S)-1-[4-(6-methylpyridin-2-yl)piperazin-1-yl]-1-oxo-6-(prop-2-enoylamino)hexan-2-yl]carbamate
• CAS: 1400654-87-6
• 化学式: C₂₇H₃₅N₅O₄
• 分子量: 493.606
• InChiKey: NUNGLKIUBOOREC-QHCPKHFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  36
• 可旋转键数：
  12
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  104
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  N-alpha-叔丁氧羰基-L-赖氨酸 在 盐酸 、 1-羟基苯并三唑 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 sodium hydroxide 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 18.5h， 生成 benzyl N-[(2S)-1-[4-(6-methylpyridin-2-yl)piperazin-1-yl]-1-oxo-6-(prop-2-enoylamino)hexan-2-yl]carbamate
  参考文献：
  名称：

  SAR Development of Lysine-Based Irreversible Inhibitors of Transglutaminase 2 for Huntington's Disease

  摘要：

  We report a series of irreversible transglutaminase 2 inhibitors starting from a known lysine dipeptide bearing an acrylamide warhead. We established new SARs resulting in compounds demonstrating improved potency and better physical and calculated properties. Transglutaminase selectivity profiling and in vitro ADME properties of selected compounds are also reported.

  DOI：

  10.1021/ml300241m

文献信息

• TRANSGLUTAMINASE TG2 INHIBITORS, PHARMACEUTICAL COMPOSITIONS, AND METHODS OF USE THEREOF
  申请人：DOMINGUEZ Celia

  公开号：US20150232420A1

  公开（公告）日：2015-08-20

  Certain compounds and pharmaceutically acceptable salts are provided herein. Also provided are pharmaceutical compositions comprising at least one compound or pharmaceutically acceptable salt therein and one or more pharmaceutically acceptable vehicle. Methods of treating patients suffering from certain disease states responsive to the inhibition of transglutaminase TG2 activity are described. These disease states include neurodegenerative disorders such as Huntington's disease. Also described are methods of treatment include administering at least one compound or pharmaceutically acceptable salt thereof as a single active agent or administering at least one compound or pharmaceutically acceptable salt thereof in combination with one or more other therapeutic agents.

  本文提供了某些化合物和药用可接受盐。还提供了包含至少一种化合物或药用可接受盐和一个或多个药用可接受载体的药物组合物。描述了治疗对抑制转谷氨酰胺酶TG2活性有响应的某些疾病状态的方法。这些疾病状态包括亨廷顿病等神经退行性疾病。还描述了治疗方法，包括单独使用至少一种化合物或药用可接受盐作为活性剂或与一个或多个其他治疗剂联合使用至少一种化合物或药用可接受盐。
• SAR Development of Lysine-Based Irreversible Inhibitors of Transglutaminase 2 for Huntington's Disease
  作者：John Wityak、Michael E. Prime、Frederick A. Brookfield、Stephen M. Courtney、Sayeh Erfan、Siw Johnsen、Peter D. Johnson、Marie Li、Richard W. Marston、Laura Reed、Darshan Vaidya、Sabine Schaertl、Anna Pedret-Dunn、Maria Beconi、Douglas Macdonald、Ignacio Muñoz-Sanjuan、Celia Dominguez

  DOI：10.1021/ml300241m

  日期：2012.12.13

  We report a series of irreversible transglutaminase 2 inhibitors starting from a known lysine dipeptide bearing an acrylamide warhead. We established new SARs resulting in compounds demonstrating improved potency and better physical and calculated properties. Transglutaminase selectivity profiling and in vitro ADME properties of selected compounds are also reported.