5-(2,6-dimethoxyphenyl)-1H-imidazole

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 5-(2,6-dimethoxyphenyl)-1H-imidazole
• 英文别名: 4-(2,6-Dimethoxyphenyl)-1H-imidazole
• 化学式: C₁₁H₁₂N₂O₂
• 分子量: 204.228
• InChiKey: CTHPGTGVECNXMW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  47.1
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-(2,6-dimethoxyphenyl)-1H-imidazole 在 氢溴酸 作用下， 以 水 为溶剂， 反应 10.0h， 以78%的产率得到2-(1H-imidazol-5-yl)benzene-1,3-diol
  参考文献：
  名称：

  Structure Based Development of Phenylimidazole-Derived Inhibitors of Indoleamine 2,3-Dioxygenase

  摘要：

  Indoleamine 2,3-dioxygenase (IDO) is emerging as an important new therapeutic target for the treatment of cancer, chronic viral infections, and other diseases characterized by pathological immune suppression. With the goal of developing more potent IDO inhibitors, a systematic study of 4-phenylimidazole (4-PI) derivatives was undertaken. Computational docking experiments guided design and synthesis efforts with analogues of 4-PI. In particular, three interactions of 4-PI analogues with IDO were studied: the active site entrance, the interior of the active site, and the heme iron binding. The three most potent inhibitors (1, 17, and 18) appear to exploit interactions with C129 and S167 in the interior of the active site. All three inhibitors are approximately 10-fold more potent than 4-PI. The study represents the first example of enzyme inhibitor development with the recently reported crystal structure of IDO and offers important lessons in the search for more potent inhibitors.

  DOI：

  10.1021/jm800512z
• 作为产物：
  描述：

  2-溴-1-(2,6-二甲苯基)乙酮 、 formamide 以65%的产率得到5-(2,6-dimethoxyphenyl)-1H-imidazole
  参考文献：
  名称：

  Structure Based Development of Phenylimidazole-Derived Inhibitors of Indoleamine 2,3-Dioxygenase

  摘要：

  Indoleamine 2,3-dioxygenase (IDO) is emerging as an important new therapeutic target for the treatment of cancer, chronic viral infections, and other diseases characterized by pathological immune suppression. With the goal of developing more potent IDO inhibitors, a systematic study of 4-phenylimidazole (4-PI) derivatives was undertaken. Computational docking experiments guided design and synthesis efforts with analogues of 4-PI. In particular, three interactions of 4-PI analogues with IDO were studied: the active site entrance, the interior of the active site, and the heme iron binding. The three most potent inhibitors (1, 17, and 18) appear to exploit interactions with C129 and S167 in the interior of the active site. All three inhibitors are approximately 10-fold more potent than 4-PI. The study represents the first example of enzyme inhibitor development with the recently reported crystal structure of IDO and offers important lessons in the search for more potent inhibitors.

  DOI：

  10.1021/jm800512z

文献信息

• IDO Inhibitors
  申请人：Mautino Mario R.

  公开号：US20110136796A1

  公开（公告）日：2011-06-09

  Presently provided are compounds according to the formula (I) or (II), and pharmaceutical compositions comprising the compounds, wherein R 1 , R 4 , and R 5 are defined herein. Such compounds and compositions are useful for modulating an activity of indoleamine 2,3-dioxygenase; treating indoleamine 2,3-dioxygenase (IDO) mediated immunosuppression; treating a medical conditions that benefit from the inhibition of enzymatic activity of indoleamine -2,3-dioxygenase; enhancing the effectiveness of an anti-cancer treatment comprising administering an anti-cancer agent; treating tumor-specific immunosuppression associated with cancer; and treating immunosupression associated with an infectious disease.

  目前提供了按照公式(I)或(II)定义的化合物以及含有这些化合物的药物组合物，其中R1、R4和R5的定义在此处。这些化合物和组合物对于调节吲哚胺2,3-二氧化酶的活性；治疗吲哚胺2,3-二氧化酶(IDO)介导的免疫抑制；治疗从抑制吲哚胺-2,3-二氧化酶的酶活性中获益的医疗状况；增强包括给予抗癌剂的抗癌治疗的有效性；治疗与癌症相关的肿瘤特异性免疫抑制；以及治疗与传染性疾病相关的免疫抑制具有用处。
• US8748469B2
  申请人：——

  公开号：US8748469B2

  公开（公告）日：2014-06-10
• US9174942B2
  申请人：——

  公开号：US9174942B2

  公开（公告）日：2015-11-03
• [EN] IDO INHIBITORS<br/>[FR] INHIBITEURS DE L'IDO
  申请人：NEWLINK GENETICS

  公开号：WO2009132238A2

  公开（公告）日：2009-10-29

  Presently provided are compounds according to the formula (I) or (II), and pharmaceutical compositions comprising the compounds, wherein R1, R4, and R5 are defined herein. Such compounds and compositions are useful for modulating an activity of indoleamine 2,3-dioxygenase; treating indoleamine 2,3-dioxygenase (IDO) mediated immunosuppression; treating a medical conditions that benefit from the inhibition of enzymatic activity of indoleamine -2,3-dioxygenase; enhancing the effectiveness of an anti- cancer treatment comprising administering an anti-cancer agent; treating tumor-specific immunosuppression associated with cancer; and treating immunosupression associated with an infectious disease.
• Structure Based Development of Phenylimidazole-Derived Inhibitors of Indoleamine 2,3-Dioxygenase
  作者：Sanjeev Kumar、Daniel Jaller、Bhumika Patel、Judith M. LaLonde、James B. DuHadaway、William P. Malachowski、George C. Prendergast、Alexander J. Muller

  DOI：10.1021/jm800512z

  日期：2008.8.1

  Indoleamine 2,3-dioxygenase (IDO) is emerging as an important new therapeutic target for the treatment of cancer, chronic viral infections, and other diseases characterized by pathological immune suppression. With the goal of developing more potent IDO inhibitors, a systematic study of 4-phenylimidazole (4-PI) derivatives was undertaken. Computational docking experiments guided design and synthesis efforts with analogues of 4-PI. In particular, three interactions of 4-PI analogues with IDO were studied: the active site entrance, the interior of the active site, and the heme iron binding. The three most potent inhibitors (1, 17, and 18) appear to exploit interactions with C129 and S167 in the interior of the active site. All three inhibitors are approximately 10-fold more potent than 4-PI. The study represents the first example of enzyme inhibitor development with the recently reported crystal structure of IDO and offers important lessons in the search for more potent inhibitors.