ethyl 1-cyclopropyl-5-hydroxy-2-methylindole-3-carboxylate | 301173-79-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: ethyl 1-cyclopropyl-5-hydroxy-2-methylindole-3-carboxylate
• 英文别名: 1-cyclopropyl-5-hydroxy-2-methyl-1H-indole-3-carboxylic acid ethyl ester
• CAS: 301173-79-5
• 化学式: C₁₅H₁₇NO₃
• 分子量: 259.305
• InChiKey: DZYVXFNCEKBKJL-UHFFFAOYSA-N

物化性质

• 沸点：
  442.9±40.0 °C(Predicted)
• 密度：
  1.30±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  51.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ethyl 1-cyclopropyl-5-hydroxy-2-methylindole-3-carboxylate 在 过氧化苯甲酰 吡啶 、 氢氧化钾 、 溴 、 溶剂黄146 作用下， 以 甲醇 、 四氯化碳 、 水 、 丙酮 为溶剂， 反应 27.0h， 生成 Ethyl 6-bromo-1-cyclopropyl-4-[(dimethylamino)methyl]-5-hydroxy-2-[[3-(trifluoromethyl)phenyl]sulfanylmethyl]indole-3-carboxylate
  参考文献：
  名称：

  5-Hydroxyindole-3-Carboxylate Derivatives and Uses Thereof

  摘要：

  本发明涉及式I的5-羟基吲哚-3-羧酸酯衍生物，或其外消旋混合物、光学异构体或药学上可接受的盐和/或水合物，其中：取代基R1、R2、Z、X和Y如描述中所定义。式I的化合物可用于制备治疗和/或预防病毒感染的药物，特别是用于制备抗HBV（乙型肝炎病毒）和抗HIV（人类免疫缺陷病毒）药物。

  公开号：

  US20080249155A1
• 作为产物：
  描述：

  乙酰乙酸乙酯 在 sodium hydroxide 作用下， 以 乙醚 、 水 、 1,2-二氯乙烷 为溶剂， 反应 25.0h， 生成 ethyl 1-cyclopropyl-5-hydroxy-2-methylindole-3-carboxylate
  参考文献：
  名称：

  5-Hydroxyindole-3-Carboxylate Derivatives and Uses Thereof

  摘要：

  本发明涉及式I的5-羟基吲哚-3-羧酸酯衍生物，或其外消旋混合物、光学异构体或药学上可接受的盐和/或水合物，其中：取代基R1、R2、Z、X和Y如描述中所定义。式I的化合物可用于制备治疗和/或预防病毒感染的药物，特别是用于制备抗HBV（乙型肝炎病毒）和抗HIV（人类免疫缺陷病毒）药物。

  公开号：

  US20080249155A1

文献信息

• Controlling the rates of reductively-activated elimination from the (indol-3-yl)methyl position of indolequinones
  作者：Steven A. Everett、Matthew A. Naylor、Paola Barraja、Elizabeth Swann、Kantilal B. Patel、Michael R. L. Stratford、Anna R. Hudnott、Borivoj Vojnovic、Rosalind J. Locke、Peter Wardman、Christopher J. Moody

  DOI：10.1039/b009652k

  日期：——

  A series of substituted 3-(4-nitrophenyloxy)methylindole-4,7-diones (Q) were synthesised. The effects of substitution patterns on the indole core on rates of elimination of 4-nitrophenol as a model for drug release following fragmentation of a phenolic ether linker were studied. After reduction to either the radical anion (Q˙−) or hydroquinone (QH2) elimination of 4-nitrophenol occurred from the (indol-3-yl)methyl position. The half-lives of Q˙− radicals at [O2] ≈ 5 µmol dm−3, typical of tumour hypoxia, were t½ ≈ 0.3–1.8 ms, the higher values associated with higher reduction potentials. Half-lives for the autoxidation of the QH2 were markedly longer at the same oxygen concentration (t½ ≈ 8–102 min) and longer still in the presence of 4 µmol dm−3 superoxide dismutase (t½ ≈ 8–19 h). Although the indolequinones were able to eliminate 4-nitrophenol with high efficiency only Q˙− radicals of the 3-carbinyl substituted derivatives did so with sufficiently short half-lives (t½ ≈ 41–2 ms) to compete with electron transfer to oxygen and therefore have the potential to target the leaving group to hypoxic tissue. The hydroquinones are not sufficiently oxygen sensitive to prevent the elimination of 4-nitrophenol (t½ ≈ 1.5–3.5 s) even at oxygen concentrations expected in normal tissue. By incorporating electron rich substituents at the indolyl carbinyl position it is possible to control the rate of reductive fragmentation. This may prove an important factor in the design of an indolequinone-based bioreductive drug delivery system.

  合成了一系列取代的3-(4-硝基苯氧基)甲基吲哚-4,7-二酮（Q）。研究了取代模式对吲哚核心在4-硝基苯酚释放速率上的影响，作为药物释放的模型，药物释放是通过酚醚连接链的断裂发生的。在还原为自由基阴离子（Q˙−）或氢醌（QH2）后，4-硝基苯酚从（吲哚-3-基）甲基位置释放。Q˙−自由基在[O2] ≈ 5 µmol dm−3（典型的肿瘤缺氧环境）下的半衰期为t½ ≈ 0.3–1.8毫秒，较高的半衰期值与较高的还原电位相关。在相同的氧浓度下，QH2的自氧化半衰期明显更长（t½ ≈ 8–102分钟），在存在4 µmol dm−3超氧化物歧化酶的情况下更长（t½ ≈ 8–19小时）。尽管吲哚醌能够以高效率释放4-硝基苯酚，但仅有3-羧基取代的Q˙−自由基具有足够短的半衰期（t½ ≈ 41–2毫秒）以与氧的电子转移竞争，因此具有将离去基团靶向缺氧组织的潜力。即使在正常组织中预期的氧浓度下，氢醌的氧敏感性不足以阻止4-硝基苯酚的释放（t½ ≈ 1.5–3.5秒）。通过在吲哚基甲基位置引入富电子取代基，可以控制还原性碎裂的速率。这可能成为设计基于吲哚醌的生物还原药物递送系统的重要因素。
• Synthesis and Antiviral Activity of Substituted Ethyl-2-Aminomethyl-5-Hydroxy-1H-Indole-3-Carboxylic Acids and Their Derivatives
  作者：A. V. Ivachtchenko、P. M. Yamanushkin、O. D. Mitkin、V. M. Kisil、O. M. Korzinov、V. Yu. Vedenskii、I. A. Leneva、E. A. Bulanova、V. V. Bichko、I. M. Okun’、A. A. Ivashchenko、Ya. A. Ivanenkov

  DOI：10.1007/s11094-015-1244-6

  日期：2015.6

  Novel substituted 5-hydroxy-2-aminomethyl-1H-indole-3-carboxylic acids and their derivatives were synthesized. The antiviral properties of these compounds were investigated in relation to bovine viral diarrhea virus (BVDV), hepatitis C virus (HCV), and influenza A/Aichi/2/69 (H3N2) virus. Of the compounds synthesized here, only the 5-hydroxy-2-(dimethylaminomethyl)-1-methyl-6-pyridin-3-yl- and 5-hydroxy-2-(dimethylaminomethyl)-1-methyl-6-fluoro-1H-indole-3-carboxylic acid ethyl ester hydrochlorides had significant activity against these viruses, these agents not only suppressing the replication of influenza A/Aichi/2/69 (H3N2) virus in cell cultures at micromolar concentrations, but also demonstrating high efficacy, greater than that of Arbidol, in a model of influenza pneumonia in mice infected with influenza A/Aichi/2/69 (H3N2) virus, when given at a dose of 25 mg/kg/day.

  合成了新型取代的 5-hydroxy-2-aminomethyl-1H-indole-3-carboxylic acids 及其衍生物。研究了这些化合物对牛病毒性腹泻病毒（BVDV）、丙型肝炎病毒（HCV）和甲型/Aichi/2/69（H3N2）流感病毒的抗病毒特性。在合成的化合物中，只有 5-羟基-2-（二甲基氨基甲基）-1-甲基-6-吡啶-3-基和 5-羟基-2-（二甲基氨基甲基）-1-甲基-6-氟-1H-吲哚-3-羧酸乙酯盐酸盐对这些病毒具有显著的活性、这些制剂不仅能在微摩尔浓度下抑制甲型/Aichi/2/69（H3N2）流感病毒在细胞培养物中的复制，而且在感染甲型/Aichi/2/69（H3N2）流感病毒的小鼠流感性肺炎模型中，以 25 毫克/千克/天的剂量给药，也能显示出比 Arbidol 更高的疗效。
• Synthesis and in vitro anti-hepatitis B virus activities of some ethyl 6-bromo-5-hydroxy-1H-indole-3-carboxylates
  作者：Huifang Chai、Yanfang Zhao、Chunshen Zhao、Ping Gong

  DOI：10.1016/j.bmc.2005.08.041

  日期：2006.2

  A series of ethyl 6-bromo-5-hydroxy-1H-indole-3-carboxylates, 8a-11v, were synthesized and evaluated for their anti-hepatitis B virus (HBV) activities in 2.2.15 cells. The selective indexes of inhibition on replication of HBV DNA of compounds 11s (>8.7) and 11t (10.8), which were introduced halogen on the phenyl ring at position 2, were greater than those of the other evaluated compounds including

  合成了一系列6-溴-5-羟基-1H-吲哚-3-羧酸乙酯8a-11v，并评估了它们在2.2.15细胞中的抗乙型肝炎病毒（HBV）活性。在位置2的苯环上引入卤素的化合物11s（> 8.7）和11t（10.8）对HBV DNA复制的抑制选择性指数大于包括拉米夫定（7.0）在内的其他评估化合物。化合物9e，9h，9l和11v表现出显着的抗HBV活性，这些化合物复制HBV DNA的IC（50）值分别为3.6、6.37、5.2和5.4 microg / ml，远高于这些。比阳性对照拉米夫定的效价228微克/毫升。
• Compounds and Methods for Modulating Fx-Receptors
  申请人：Bell Michael Gregory

  公开号：US20080306125A1

  公开（公告）日：2008-12-11

  Compounds of formula. wherein variables are as defined herein and their pharmaceutical compositions and methods of use are disclosed as useful for treating dyslipidemia and related diseases.

  本发明涉及化合物的公式，其中变量如本文所定义，以及它们的药物组合物和使用方法，可用于治疗血脂异常和相关疾病。
• Compounds and methods for modulating FX-receptors
  申请人：Eli Lilly and Company

  公开号：US07863302B2

  公开（公告）日：2011-01-04

  Compounds of formula and their pharmaceutical compositions and methods of use are disclosed as useful for treating dyslipidemia and related diseases.

  本发明揭示了一种公式为的化合物及其制药组合物和使用方法，可用于治疗血脂异常和相关疾病。