1-环己基甲基-5-(羟甲基)咪唑 | 226930-90-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 1-环己基甲基-5-(羟甲基)咪唑
• 英文名称: 1-cyclohexylmethyl-5-(hydroxymethyl)imidazole
• 英文别名: 5-Hydroxymethyl-1-cyclohexylmethylimidazole；1-(Cyclohexylmethyl)-1H-imidazole-5-methanol；[3-(cyclohexylmethyl)imidazol-4-yl]methanol
• CAS: 226930-90-1
• 化学式: C₁₁H₁₈N₂O
• 分子量: 194.277
• InChiKey: NTKHPXKHYKQVSE-UHFFFAOYSA-N

物化性质

• 熔点：
  111-114 °C
• 沸点：
  396.0±17.0 °C(Predicted)
• 密度：
  1.17±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  38
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-环己基甲基-5-(羟甲基)咪唑 在 lithium hydroxide 、 manganase dioxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 为溶剂， 生成 FTI-2238
  参考文献：
  名称：

  Design and Synthesis of Peptidomimetic Protein Farnesyltransferase Inhibitors as Anti-Trypanosoma brucei Agents

  摘要：

  On the basis of the structure of the CVIM tetrapeptide substrate of mammalian protein farnesyltransferase, a series of imidazole-containing peptidomimetics was designed and synthesized, and their inhibition activity against Trypanosoma brucel protein farnesyltransferase (TbPFT) was evaluated. Peptidomimetics where the 5-position of the imidazole ring was linked to the hydrophobic scaffold showed over 70% inhibition activity at 50 nM in the enzyme assay, whereas the corresponding C-4 regioisomers were less potent. The ester prodrug 23 was found to be a potent inhibitor against cultured Trypanosoma brucei brucei and Trypanosoma brucei rhodesiense cells with ED50 values of 0.025 and 0.0026 muM, respectively. Furthermore introducing a second imidazole group into 23 led to 31, which showed the highest inhibition activity against the parasite with an ED50 of 0.0015 muM. The potency of the TbPFT inhibitors and the cytotoxicity of the corresponding esters to T. brucei cells were shown to be highly correlated. These studies validate TbPFT as a target for the development of novel therapeutics against African sleeping sickness.

  DOI：

  10.1021/jm030236o
• 作为产物：
  描述：

  4-羟甲基咪唑盐酸盐 、 溴甲基环己烷 在 sodium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以5%的产率得到1-环己基甲基-5-(羟甲基)咪唑
  参考文献：
  名称：

  Design and Synthesis of Peptidomimetic Protein Farnesyltransferase Inhibitors as Anti-Trypanosoma brucei Agents

  摘要：

  On the basis of the structure of the CVIM tetrapeptide substrate of mammalian protein farnesyltransferase, a series of imidazole-containing peptidomimetics was designed and synthesized, and their inhibition activity against Trypanosoma brucel protein farnesyltransferase (TbPFT) was evaluated. Peptidomimetics where the 5-position of the imidazole ring was linked to the hydrophobic scaffold showed over 70% inhibition activity at 50 nM in the enzyme assay, whereas the corresponding C-4 regioisomers were less potent. The ester prodrug 23 was found to be a potent inhibitor against cultured Trypanosoma brucei brucei and Trypanosoma brucei rhodesiense cells with ED50 values of 0.025 and 0.0026 muM, respectively. Furthermore introducing a second imidazole group into 23 led to 31, which showed the highest inhibition activity against the parasite with an ED50 of 0.0015 muM. The potency of the TbPFT inhibitors and the cytotoxicity of the corresponding esters to T. brucei cells were shown to be highly correlated. These studies validate TbPFT as a target for the development of novel therapeutics against African sleeping sickness.

  DOI：

  10.1021/jm030236o

文献信息

• Imidazole derivatives having an inhibitory activity for farnesyl transferase and process for preparation thereof
  申请人：LG Chemical Ltd.

  公开号：US06268363B1

  公开（公告）日：2001-07-31

  The present invention relates to a novel imidazole derivative represented by formula (1) which shows an inhibitory activity against farnesyl transferase or pharmaceutically acceptable salts or isomers thereof, in which A, n1 and Y are defined in the specification; to a process for preparation of the compound of formula (1); to intermediates which are used in the preparation of the compound of formula (1); and to a pharmaceutical composition comprising the compound of formula (1) as an active ingredient.

  本发明涉及一种新型咪唑衍生物，其化学式表示为（1），该化合物对法尼基转移酶具有抑制活性，或者其药学上可接受的盐或同分异构体，其中A、n1和Y在规范中有定义；制备化合物（1）的方法；用于制备化合物（1）的中间体；以及包含化合物（1）作为活性成分的药物组合物。
• IMIDAZOLE DERIVATIVES HAVING AN INHIBITORY ACTIVITY FOR FARNESYL TRANSFERASE AND PROCESS FOR PREPARATION THEREOF
  申请人：LG CHEMICAL LIMITED

  公开号：EP1045846B1

  公开（公告）日：2003-05-02
• US6268363B1
  申请人：——

  公开号：US6268363B1

  公开（公告）日：2001-07-31
• US6472526B1
  申请人：——

  公开号：US6472526B1

  公开（公告）日：2002-10-29
• US6518429B2
  申请人：——

  公开号：US6518429B2

  公开（公告）日：2003-02-11