5-(4-甲基苯基)噻唑并[2,3-c]-1,2,4-三唑-3(2H)-硫酮 | 500112-74-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 三唑并噻唑类
• 中文名称: 5-(4-甲基苯基)噻唑并[2,3-c]-1,2,4-三唑-3(2H)-硫酮
• 英文名称: 5-(4'-tolyl)thiazolo[2.3-c][1.2.4]triazole-3-thiol
• 英文别名: 5-(4-Methylphenyl)[1,3]thiazolo[2,3-c][1,2,4]triazole-3-thiol；5-(4-methylphenyl)-2H-[1,3]thiazolo[2,3-c][1,2,4]triazole-3-thione
• CAS: 500112-74-3
• 化学式: C₁₁H₉N₃S₂
• mdl: MFCD06254379
• 分子量: 247.345
• InChiKey: LNDYWRMGFKFDTC-UHFFFAOYSA-N

物化性质

• 熔点：
  194-195℃

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  85
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-(4-甲基苯基)噻唑并[2,3-c]-1,2,4-三唑-3(2H)-硫酮 、 碘甲烷 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 以99%的产率得到3-(methylthio)-5-(4'-tolyl)thiazolo[2.3-c][1.2.4]triazole
  参考文献：
  名称：

  Crystal Structures and Structure–Activity Relationships of Imidazothiazole Derivatives as IDO1 Inhibitors

  摘要：

  Indoleamine 2,3-dioxygenase 1 (IDO1) is considered as a promising target for the treatment of several diseases, including neurological disorders and cancer. We report here the crystal structures of two IDO1/IDO1 inhibitor complexes, one of which shows that Amg-1 is directly bound to the heme iron of IDO1 with a clear induced fit. We also describe the identification and preliminary optimization of imidazothiazole derivatives as novel IDO1 inhibitors. Using our crystal structure information and structure activity relationships (SAR) at the pocket-B of IDO I, we found a series of urea derivatives as potent IDO1 inhibitors and revealed that generation of an induced fit and the resulting interaction with Phe226 and Arg231 are essential for potent IDO1 inhibitory activity. The results of this study are very valuable for understanding the mechanism of IDOI activation, which is very important for structure-based drug design (SBDD) to discover potent IDO1 inhibitors.

  DOI：

  10.1021/ml500247w

文献信息

• Crystal Structures and Structure–Activity Relationships of Imidazothiazole Derivatives as IDO1 Inhibitors
  作者：Shingo Tojo、Tetsuya Kohno、Tomoyuki Tanaka、Seiji Kamioka、Yosuke Ota、Takayuki Ishii、Keiko Kamimoto、Shigehiro Asano、Yoshiaki Isobe

  DOI：10.1021/ml500247w

  日期：2014.10.9

  Indoleamine 2,3-dioxygenase 1 (IDO1) is considered as a promising target for the treatment of several diseases, including neurological disorders and cancer. We report here the crystal structures of two IDO1/IDO1 inhibitor complexes, one of which shows that Amg-1 is directly bound to the heme iron of IDO1 with a clear induced fit. We also describe the identification and preliminary optimization of imidazothiazole derivatives as novel IDO1 inhibitors. Using our crystal structure information and structure activity relationships (SAR) at the pocket-B of IDO I, we found a series of urea derivatives as potent IDO1 inhibitors and revealed that generation of an induced fit and the resulting interaction with Phe226 and Arg231 are essential for potent IDO1 inhibitory activity. The results of this study are very valuable for understanding the mechanism of IDOI activation, which is very important for structure-based drug design (SBDD) to discover potent IDO1 inhibitors.