4-(4-ethynyl)thiazol-2-amine | 1566004-69-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4-(4-ethynyl)thiazol-2-amine
• 英文别名: 2-Thiazolamine, 4-ethynyl-；4-ethynyl-1,3-thiazol-2-amine
• CAS: 1566004-69-0
• 化学式: C₅H₄N₂S
• 分子量: 124.166
• InChiKey: PCRSUVABZDKOLW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  8
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  67.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(4-ethynyl)thiazol-2-amine 、 叔丁氧羰基-3-(4-噻唑基)-L-丙氨酸 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 生成
  参考文献：
  名称：

  Design, Synthesis, and Optimization of Novel Epoxide Incorporating Peptidomimetics as Selective Calpain Inhibitors

  摘要：

  Hyperactivation of the calcium-dependent cysteine protease calpain 1 (Call) is implicated as a primary or secondary pathological event in a wide range of illnesses and in neurodegenerative states, including Alzheimer's disease (AD). E-64 is an epoxide-containing natural product identified as a potent nonselective, calpain inhibitor, with demonstrated efficacy in animal models of AD. By use of E-64 as a lead, three successive generations of calpain inhibitors were developed using computationally assisted design to increase selectivity for Call. First generation analogues were potent inhibitors, effecting covalent modification of recombinant Call catalytic domain (Call(cat)), demonstrated using LC-MS/MS. Refinement yielded second generation inhibitors with improved selectivity. Further library expansion and ligand refinement gave three Call inhibitors, one of which was designed as an activity-based protein profiling probe. These were determined to be irreversible and selective inhibitors by kinetics studies comparing full length Call with the genera l cysteine protease papain.

  DOI：

  10.1021/jm4006719