5-ethylimidazole-4-carboxaldehyde | 97749-73-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 5-ethylimidazole-4-carboxaldehyde
• 英文别名: 5-ethyl-1H-imidazole-4-carbaldehyde
• CAS: 97749-73-0
• 化学式: C₆H₈N₂O
• mdl: MFCD13192160
• 分子量: 124.142
• InChiKey: NDSLJTCGKXNUAS-UHFFFAOYSA-N

物化性质

• 熔点：
  136-137 °C
• 沸点：
  337.7±22.0 °C(Predicted)
• 密度：
  1.177±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  9
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.333
• 拓扑面积：
  45.8
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-ethylimidazole-4-carboxaldehyde 在 4 A molecular sieve 、 sodium hydride 、 溶剂黄146 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 3.5h， 生成 9-methyl-3-[(5-ethylimidazol-4-yl)methylene]-2,3,4,9-tetrahydrothiopyrano[2,3-b]indol-4-one
  参考文献：
  名称：

  新型5-羟色胺（5-HT3）受体拮抗剂。9-甲基-2,3,4,9-四氢噻喃并[2,3-b]吲哚-4-酮衍生物的合成及构效关系。

  摘要：

  新型9-甲基-4,9-二氢噻喃并[2,3-b]吲哚-4-one衍生物2b-e，3-亚甲基-9-甲基-2,3,4,9-四氢噻喃并[2,3-b制备了]吲哚-4-on e衍生物3b-e和9-甲基-2,3,4,9-四氢噻喃并[2,3-b]吲哚-4-one衍生物4a-e。使用von Bezold-Jarisch反射试验（BJ反射，大鼠）和离体远端结肠（豚鼠）对5-HT的收缩反应，评估了这些化合物的5-羟色胺（5-HT3）受体拮抗活性。 。在BJ反射测试中（ID50 = 0.048微克/千克，iv），发现5-乙基-4-咪唑基衍生物4d的效力是昂丹西酮1的79倍，发现5-甲基-4-咪唑基衍生物4c在结肠收缩（IC50 = 0.0062 microM）分析中，其效力是1的126倍。

  DOI：

  10.1248/cpb.45.101
• 作为产物：
  描述：

  丙酰乙酸乙酯 在 manganese(IV) oxide 、 lithium aluminium tetrahydride 、 磺酰氯 作用下， 以 四氢呋喃 、 氯仿 、 水 、 丙酮 为溶剂， 反应 22.5h， 生成 5-ethylimidazole-4-carboxaldehyde
  参考文献：
  名称：

  Imidazole-based pinanamine derivatives: Discovery of dual inhibitors of the wild-type and drug-resistant mutant of the influenza A virus

  摘要：

  We previously reported potent hit compound 4 inhibiting the wild-type influenza A virus A/HK/68 (H3N2) and A/M2-S31N mutant viruses A/WS/33 (H1N1), with its latter activity quite weak. To further increase its potency, a structure-activity relationship study of a series of imidazole-linked pinanamine derivatives was conducted by modifying the imidazole ring of this compound. Several compounds of this series inhibited the amantadine-sensitive virus at low micromolar concentrations. Among them, 33 was the most potent compound, which was identified as being active on an amantadine-sensitive virus through blocking of the viral M2 ion channel. Furthermore, 33 markedly inhibited the amantadine-resistant virus (IC50 = 3.4 mu M) and its activity increased by almost 24-fold compared to initial compound, with its action mechanism being not M2 channel mediated. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.12.013

文献信息

• Inhibitors of Tumor Progression Loci-2 (Tpl2) Kinase and Tumor Necrosis Factor α (TNF-α) Production:  Selectivity and in Vivo Antiinflammatory Activity of Novel 8-Substituted-4-anilino-6-aminoquinoline-3-carbonitriles
  作者：Neal Green、Yonghan Hu、Kristin Janz、Huan-Qiu Li、Neelu Kaila、Satenig Guler、Jennifer Thomason、Diane Joseph-McCarthy、Steve Y. Tam、Rajeev Hotchandani、Junjun Wu、Adrian Huang、Qin Wang、Louis Leung、Jefferey Pelker、Suzana Marusic、Sang Hsu、Jean-Baptiste Telliez、J. Perry Hall、John W. Cuozzo、Lih-Ling Lin

  DOI：10.1021/jm070436q

  日期：2007.9.1

  involved in diseases such as rheumatoid arthritis. Initial 4-anilino-6-aminoquinoline-3-carbonitrile leads showed poor selectivity for Tpl2 over epidermal growth factor receptor (EGFR) kinase. Using molecular modeling and crystallographic data of the EGFR kinase domain with and without an EGFR kinase-specific 4-anilinoquinazoline inhibitor (erlotinib, Tarceva), we hypothesized that we could diminish the

  肿瘤进展基因座2（Tpl2）（Cot / MAP3K8）是MAP3K家族中位于MEK上游的丝氨酸/苏氨酸激酶。最近使用Tpl2敲除小鼠的研究表明Tpl2在脂多糖（LPS）诱导的肿瘤坏死因子α（TNF-alpha）和其他与风湿性关节炎等疾病有关的促炎细胞因子的产生中具有重要作用。最初的4-苯胺基-6-氨基喹啉-3-甲腈导线显示出对Tpl2的选择性较表皮生长因子受体（EGFR）激酶差。使用和不使用EGFR激酶特异性4-苯胺基喹唑啉抑制剂（erlotinib，Tarceva）的EGFR激酶结构域的分子模型和晶体学数据，我们假设我们可以通过在C-8位置进行取代来减少对EGFR激酶的抑制作用4-苯胺基-6-氨基喹啉-3-腈引线。由适当的2-取代的4-硝基苯胺制备8-取代的4-苯胺基-6-氨基喹啉-3-甲腈。对C-6和C-8位置的修饰导致鉴定了对LPS刺激的大鼠和人类血液中TNF-α释放抑制作用增强的
• 3-Cyanoquinoline inhibitors of Tpl2 kinase and methods of making and using the same
  申请人：Green Jeffrey Neal

  公开号：US20060264460A1

  公开（公告）日：2006-11-23

  The present invention provides compounds of formula (I): and pharmaceutically acceptable salts thereof, wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , m and n are defined as described herein. The invention also provides methods of making the compounds of formula (I), and methods of treating inflammatory diseases, such as rheumatoid arthritis, in a mammal comprising administering a therapeutically effective amount of a compound of formula (I) to the mammal.

  本发明提供了如下式（I）的化合物及其药用可接受的盐，其中R1、R2、R3、R4、R5、R6、R7、R8、m和n的定义如本文所述。该发明还提供了制备如式（I）化合物的方法，以及治疗炎症性疾病（如类风湿性关节炎）的方法，包括向哺乳动物施用如式（I）化合物的治疗有效量。
• PAUL, R.;BROCKMAN, J. A.;HALLETT, W. A.;HANIFIN, J. W.;TARRANT, M. E.;TOR+, J. MED. CHEM., 1985, 28, N 11, 1704-1716
  作者：PAUL, R.、BROCKMAN, J. A.、HALLETT, W. A.、HANIFIN, J. W.、TARRANT, M. E.、TOR+

  DOI：——

  日期：——
• Imidazole-based pinanamine derivatives: Discovery of dual inhibitors of the wild-type and drug-resistant mutant of the influenza A virus
  作者：Jianghong Dong、Shengwei Chen、Runfeng Li、Wei Cui、Haiming Jiang、Yixia Ling、Zifeng Yang、Wenhui Hu

  DOI：10.1016/j.ejmech.2015.12.013

  日期：2016.1

  We previously reported potent hit compound 4 inhibiting the wild-type influenza A virus A/HK/68 (H3N2) and A/M2-S31N mutant viruses A/WS/33 (H1N1), with its latter activity quite weak. To further increase its potency, a structure-activity relationship study of a series of imidazole-linked pinanamine derivatives was conducted by modifying the imidazole ring of this compound. Several compounds of this series inhibited the amantadine-sensitive virus at low micromolar concentrations. Among them, 33 was the most potent compound, which was identified as being active on an amantadine-sensitive virus through blocking of the viral M2 ion channel. Furthermore, 33 markedly inhibited the amantadine-resistant virus (IC50 = 3.4 mu M) and its activity increased by almost 24-fold compared to initial compound, with its action mechanism being not M2 channel mediated. (C) 2015 Elsevier Masson SAS. All rights reserved.
• Novel 5-Hydroxytryptamine (5-HT3) Receptor Antagonists. Synthesis and Structure-Activity Relationships of 9-Methyl-2,3,4,9-tetrahydrothiopyrano(2,3-b)indol-4-one Derivatives.
  作者：Takeshi SUZUKI、Akira MATSUHISA、Keiji MIYATA、Isao YANAGISAWA、Mitsuaki OHTA

  DOI：10.1248/cpb.45.101

  日期：——

  Novel 9-methyl-4,9-dihydrothiopyrano[2,3-b]indol-4-one derivatives 2b-e, 3-methylene-9-methyl-2,3,4,9-tetrahydrothiopyrano[2,3-b]indol-4-on e derivatives 3b-e and 9-methyl-2,3,4,9-tetrahydrothiopyrano[2,3-b]indol-4-one derivatives 4a-e were prepared. The 5-hydroxytryptamine (5-HT3) receptor-antagonistic activities of these compounds were evaluated by using the von Bezold-Jarisch reflex test (B. J.

  新型9-甲基-4,9-二氢噻喃并[2,3-b]吲哚-4-one衍生物2b-e，3-亚甲基-9-甲基-2,3,4,9-四氢噻喃并[2,3-b制备了]吲哚-4-on e衍生物3b-e和9-甲基-2,3,4,9-四氢噻喃并[2,3-b]吲哚-4-one衍生物4a-e。使用von Bezold-Jarisch反射试验（BJ反射，大鼠）和离体远端结肠（豚鼠）对5-HT的收缩反应，评估了这些化合物的5-羟色胺（5-HT3）受体拮抗活性。 。在BJ反射测试中（ID50 = 0.048微克/千克，iv），发现5-乙基-4-咪唑基衍生物4d的效力是昂丹西酮1的79倍，发现5-甲基-4-咪唑基衍生物4c在结肠收缩（IC50 = 0.0062 microM）分析中，其效力是1的126倍。