1-戊基-1H-咪唑-5-甲醛 | 655235-90-8

• 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-戊基-1H-咪唑-5-甲醛
• 英文名称: 1-pentyl-1H-imidazole-5-carbaldehyde
• 英文别名: 1-pentyl-5-imidazolecarboxyaldehyde；N-n-pentyl-5-imidazolealdehyde；3-pentylimidazole-4-carbaldehyde
• CAS: 655235-90-8
• 化学式: C₉H₁₄N₂O
• 分子量: 166.223
• InChiKey: XWZSPKFIVMBRAW-UHFFFAOYSA-N

物化性质

• 沸点：
  327.1±15.0 °C(Predicted)
• 密度：
  1.03±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  12
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  34.9
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-戊基-1H-咪唑-5-甲醛 在 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 生成 FTI-2241
  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：

  1-戊基-5-(羟甲基)咪唑 在 manganase dioxide 作用下， 以 1,4-二氧六环 为溶剂， 生成 1-戊基-1H-咪唑-5-甲醛
  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

• 黄酮咪唑类化合物及其制备方法
  申请人：盐城师范学院

  公开号：CN107216315B

  公开（公告）日：2020-03-17

  本发明提供了一种黄酮咪唑类化合物,其通式为I、II或III，其中：R1为氢、烷基或羟基；R2为氢、烷基或羟基；R3为氢、烷基或羟基；R4为氢、烷基、取代芳香基；R5为氢或正丁基；R6为氢或氯；或上述化合物药学上可接收的盐。此外，本发明还提供了上述黄酮咪唑类化合物的制备方法。体外蛋白酪氨酸磷酸酶1B(PTP1B)活性检测结果显示，本发明合成的黄酮咪唑类化合物对PTP1B均表现出一定的抑制作用，本发明为开发以蛋白酪氨酸磷酸酶1B为靶点的2型糖尿病药物提供了基本的理论依据。该类化合物的合成路线短，制备方法简单，原料易得，成本低，因此，该类化合物有望为2型糖尿病治疗提供更多高效、安全的候选药物，有助于解决临床治疗问题。
• Identification of novel imidazole flavonoids as potent and selective inhibitors of protein tyrosine phosphatase
  作者：Ling Zhang、Yu Ge、Qing Ming Wang、Cheng-He Zhou

  DOI：10.1016/j.bioorg.2019.03.074

  日期：2019.7

  imidazole flavonoids as new type of protein tyrosine phosphatase inhibitors were synthesized and characterized. Most of them gave potent protein phosphatase 1B (PTP1B) inhibitory activities. Especially, compound 11a could effectively inhibit PTP1B with an IC50 value of 0.63 μM accompanied with high selectivity ratio (9.5-fold) over T-cell protein tyrosine phosphatase (TCPTP). This compound is cell permeable

  合成了一系列咪唑类黄酮作为新型的蛋白质酪氨酸磷酸酶抑制剂。他们大多数给予有效的蛋白磷酸酶1B（PTP1B）抑制活性。尤其是，化合物11a可以有效抑制PTP1B，IC50值为0.63μM，并且具有比T细胞蛋白酪氨酸磷酸酶（TCPTP）高的选择性（9.5倍）。该化合物是细胞可渗透的，具有较低的细胞毒性。通过分子建模和动力学研究揭示了高结合亲和力和选择性。量子化学研究证实了活性必不可少的结构特征。
• Design and Synthesis of Peptidomimetic Protein Farnesyltransferase Inhibitors as Anti-<i>Trypanosoma brucei </i>Agents
  作者：Junko Ohkanda、Frederick S. Buckner、Jeffrey W. Lockman、Kohei Yokoyama、Dora Carrico、Richard Eastman、Kate de Luca-Fradley、Wendy Davies、Simon L. Croft、Wesley C. Van Voorhis、Michael H. Gelb、Saïd M. Sebti、Andrew D. Hamilton

  DOI：10.1021/jm030236o

  日期：2004.1.1

  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.