3-(1H-indol-3-yl)-2-(methylenamino)-propanoic acid

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 3-(1H-indol-3-yl)-2-(methylenamino)-propanoic acid
• 英文别名: N^α-methylene-tryptophan; N-methylene-L-tryptophan；N^α-Methylen-tryptophan; N-Methylen-L-tryptophan；Methylentryptophan；(2S)-3-(1H-indol-3-yl)-2-(methylideneamino)propanoic acid
• 化学式: C₁₂H₁₂N₂O₂
• 分子量: 216.239
• InChiKey: GDNIGMLOAVSUIY-NSHDSACASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  65.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(1H-indol-3-yl)-2-(methylenamino)-propanoic acid 在 哌啶 、 氯化亚砜 、 三乙胺 作用下， 以 1,4-二氧六环 、 乙醚 、 乙醇 为溶剂， 反应 5.0h， 生成 2-[(1H-indol-3-yl)methyl]-5-amino-3-(phenylamino)pyridine-4-carbonitrile
  参考文献：
  名称：

  Development of new indole-derived neuroprotective agents

  摘要：

  There is a great deal of interest in neurotrophin therapy to prevent neuronal degeneration. The present study aimed at synthesizing new functionalized indole derivatives with structures justifying neuroprotective activity using L-tryptophan (TRP)(dagger) as starting material. The potential neuroprotective effect of these newly synthesized agents against acrylamide (ACR) induced neurotoxicity was investigated in adult female rats. The novel indole derivatives, indolylmethyl pyridine derivatives 9a,b, pyrimidinylindolyl propanone derivatives 12a-c, pyrazolylindolyl propanone derivatives 14a,b, and indolyl tetrazolopropanoic acid derivative 17 were synthesized and their chemical structures were confirmed by studying their analytical and spectral data. The administration of ACR [ip, 50 mg kg(-1) body weight (b. wt.)] alone resulted in significant increase in brain malondialdehyde level (MDA) and lactate dehydrogenase (LDH) activity whereas it caused significant decrease in brain monoamines levels and antioxidant enzymes activity. Treatment with the indole derivatives 9b, 12c, 14a, and 17 (ip, 50 mg kg(-1) b. wt.) prior to ACR produced neuroprotective activity with various intensities depending on the structure of each compound. Compound 17 in which the tetrazole ring was attached to the TRP moiety ranked as the strongest neuroprotective agent. All the tested compounds have been shown to possess antioxidant properties offering promising efficacy against oxidative stress induced by ACR administration. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.03.031
• 作为产物：
  描述：

  相思豆毒素 在 氧气 、 Thermomicrobium roseum sarcosine oxidase S₃₂₀K/F₂₄₃Y double mutant 作用下， 以 aq. buffer 为溶剂， 反应 2.0h， 生成 3-(1H-indol-3-yl)-2-(methylenamino)-propanoic acid
  参考文献：
  名称：

  重建关键微域的自然进化趋势为热微生物 N-去甲基酶的工程设计提供了有效策略

  摘要：

  据报道， N-去甲基化酶可以去除伯胺或仲胺上的甲基，这可能会进一步影响生物大分子或化合物的性质和功能；然而，尚未系统地研究N-去甲基化酶的底物范围和稳健性。在这里，我们报告了Thermomicrobium roseum肌氨酸氧化酶 (TrSOX) 关键微域中自然进化的再现，这是一种N-脱甲基酶具有显着的稳定性（熔化温度超过 100 °C）和对映选择性，可增强底物范围和对 -CN- 键的催化效率。对于初始框架，我们通过结晶和 X 射线衍射 (XRD) 获得了 TrSOX 的结构。然后使用祖先序列重建 (ASR) 识别关键微结构域的非保守残基（包括催化环、辅酶口袋、底物口袋和入口位点）的自然进化，并通过位点重建自然进化过程中产生的替换。定向诱变。单取代和双取代变体催化N的N-去甲基化-甲基-L-氨基酸分别比野生型快 1800 倍和 6000 倍。此外，这些单取代变体催化了非氨基酸化合物的末端N

  DOI：

  10.1016/j.jbc.2022.101656

文献信息

• Beta-(fluoromethylene)-5-hydroxytryptophan and derivatives as prodrugs for mao inhibition
  申请人：MERRELL PHARMACEUTICALS INC.

  公开号：EP0291998A2

  公开（公告）日：1988-11-23

  This invention relates to pharmacologically-active novel compounds comprising β-fluoromethylene-5-hydroxytryptophan and derivatives, to methods of inhibiting monoamine oxidase and to treating depression, and to pharmaceutical compositions containing the compounds.

  本发明涉及由β-氟亚甲基-5-羟色氨酸及其衍生物组成的具有药理活性的新型化合物、抑制单胺氧化酶和治疗抑郁症的方法，以及含有这些化合物的药物组合物。
• Development of new indole-derived neuroprotective agents
  作者：Rafat M. Mohareb、Hanaa H. Ahmed、Gamal A. Elmegeed、Mervat M. Abd-Elhalim、Reham W. Shafic

  DOI：10.1016/j.bmc.2011.03.031

  日期：2011.5

  There is a great deal of interest in neurotrophin therapy to prevent neuronal degeneration. The present study aimed at synthesizing new functionalized indole derivatives with structures justifying neuroprotective activity using L-tryptophan (TRP)(dagger) as starting material. The potential neuroprotective effect of these newly synthesized agents against acrylamide (ACR) induced neurotoxicity was investigated in adult female rats. The novel indole derivatives, indolylmethyl pyridine derivatives 9a,b, pyrimidinylindolyl propanone derivatives 12a-c, pyrazolylindolyl propanone derivatives 14a,b, and indolyl tetrazolopropanoic acid derivative 17 were synthesized and their chemical structures were confirmed by studying their analytical and spectral data. The administration of ACR [ip, 50 mg kg(-1) body weight (b. wt.)] alone resulted in significant increase in brain malondialdehyde level (MDA) and lactate dehydrogenase (LDH) activity whereas it caused significant decrease in brain monoamines levels and antioxidant enzymes activity. Treatment with the indole derivatives 9b, 12c, 14a, and 17 (ip, 50 mg kg(-1) b. wt.) prior to ACR produced neuroprotective activity with various intensities depending on the structure of each compound. Compound 17 in which the tetrazole ring was attached to the TRP moiety ranked as the strongest neuroprotective agent. All the tested compounds have been shown to possess antioxidant properties offering promising efficacy against oxidative stress induced by ACR administration. (C) 2011 Elsevier Ltd. All rights reserved.
• Recreating the natural evolutionary trend in key microdomains provides an effective strategy for engineering of a thermomicrobial N-demethylase
  作者：Yu Xin、Chen Shen、Mengwei Tang、Zitao Guo、Yi Shi、Zhenghua Gu、Jun Shao、Liang Zhang

  DOI：10.1016/j.jbc.2022.101656

  日期：2022.3

  were recreated by site-directed mutagenesis. The single and double substitution variants catalyzed the N-demethylation of N-methyl-L-amino acids up to 1800- and 6000-fold faster than the wild type, respectively. Additionally, these single substitution variants catalyzed the terminal N-demethylation of non-amino-acid compounds and the oxidation of the main chain -C-N- bond to a -C=N- bond in the nitrogen-containing

  据报道， N-去甲基化酶可以去除伯胺或仲胺上的甲基，这可能会进一步影响生物大分子或化合物的性质和功能；然而，尚未系统地研究N-去甲基化酶的底物范围和稳健性。在这里，我们报告了Thermomicrobium roseum肌氨酸氧化酶 (TrSOX) 关键微域中自然进化的再现，这是一种N-脱甲基酶具有显着的稳定性（熔化温度超过 100 °C）和对映选择性，可增强底物范围和对 -CN- 键的催化效率。对于初始框架，我们通过结晶和 X 射线衍射 (XRD) 获得了 TrSOX 的结构。然后使用祖先序列重建 (ASR) 识别关键微结构域的非保守残基（包括催化环、辅酶口袋、底物口袋和入口位点）的自然进化，并通过位点重建自然进化过程中产生的替换。定向诱变。单取代和双取代变体催化N的N-去甲基化-甲基-L-氨基酸分别比野生型快 1800 倍和 6000 倍。此外，这些单取代变体催化了非氨基酸化合物的末端N