1-(2,4,5-trihydroxyphenyl)-2-aminopropane | 41241-36-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-(2,4,5-trihydroxyphenyl)-2-aminopropane
• 英文别名: 6-hydroxydopamine；2,4,5-Trihydroxy-α-methylphenaethylamin；2,4,5-Trihydroxyamphetamine；5-(2-aminopropyl)benzene-1,2,4-triol
• CAS: 41241-36-5
• 化学式: C₉H₁₃NO₃
• mdl: MFCD01688746
• 分子量: 183.207
• InChiKey: FWNNQQDQXAMXMK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  13
• 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：
  86.7
• 氢给体数：
  4
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2,4,5-三甲氧基苯甲醛 在 ammonium acetate 作用下， 以 溶剂黄146 为溶剂， 生成 1-(2,4,5-trihydroxyphenyl)-2-aminopropane
  参考文献：
  名称：

  Catechol O-methyltransferase. 9. Mechanism of inactivation by 6-hydroxydopamine

  摘要：

  A series of methylated analogues of 6-hydroxydopamine (6-OHDA) has been synthesized and evaluated as irreversible inhibitors of catechol O-methyltransferase (COMT). These analogues have been prepared in an effort to elucidate the mechanism involved in the inactivation of this enzyme by 6-OHDA. The analogues prepared had methyl groups incorporated in the 2 and/or 5 positions of 6-OHDA so as to block nucleophilic attakc at these positions in the corresponding oxidation products [6-hydroxydopamine-p-quinone (6-OHDAQ), aminochromes I and II]. Such 2- and/or 5-methylated 6-OHDA analogues were found to be inhibitors of COMT with the inactivation apparently resulting from modification of an essential amino acid residue at the active site of the enzyme. The activity of these analogues as inhibitors of COMT argues against a mechanism involving a 1,4 Michael addition reaction by a protein nucleophile at the 2 or 5 positions on 6-OHDAQ or on the corresponding aminochromes. Instead, an alternative mechanism is proposed to explain these data, which involves attack of a protein nucleophile at the carbonyl group in the 6 position of 6-OHDAQ or at the imine functionality on aminochromes I and II. The results of the present experiments have provided insight into the mechanism involved in inactivation of COMT by 6-OHDA. In addition, this study has provided considerable insight into the chemical reactivity of the electrophilic species generated after oxidation of 6-OHDA.

  DOI：

  10.1021/jm00232a007

文献信息

• Nitrite- and Peroxide-Dependent Oxidation Pathways of Dopamine:  6-Nitrodopamine and 6-Hydroxydopamine Formation as Potential Contributory Mechanisms of Oxidative Stress- and Nitric Oxide-Induced Neurotoxicity in Neuronal Degeneration
  作者：Anna Palumbo、Alessandra Napolitano、Paolo Barone、Marco d'Ischia

  DOI：10.1021/tx990121g

  日期：1999.12.1

  presence of 1 or 2 mM H(2)O(2) with NO(2)(-) at a concentration of 0.5-10 mM resulted in the formation of 1 and 2 in up to 8 and 2 microM yields, respectively, depending on the substrate concentration and the NO(2)(-):H(2)O(2) ratio. Nitration and hydroxylation of 0.1 mM dopamine was observed with 1 mM NO(2)(-) using HRP and the D-glucose/glucose oxidase system to generate H(2)O(2) in situ. In the presence

  在亚磷酸盐离子（NO（2）（-））在磷酸盐缓冲液（pH 7. 4）中并在37摄氏度下存在时，多巴胺被多种过氧化氢（H（2）O（2））-氧化依赖的酶和化学体系，除了通过5、6-二羟基吲哚生成黑色黑色素样颜料外，还产生少量有效的神经毒素6-羟基多巴胺（1）和6-硝基多巴胺（2），即多巴胺的假定反应产物与NO衍生的物种。在存在1或2 mM H（2）O（2）和NO（2）（-）且浓度为0.5-的情况下，用辣根过氧化物酶（HRP）或乳过氧化物酶（LPO）处理0. 5或1 mM多巴胺10 mM导致形成1和2，分别高达8和2 microM的产量，具体取决于底物浓度和NO（2）（-）：H（2）O（2）的比例。硝化和羟化为0。使用HRP和D-葡萄糖/葡萄糖氧化酶系统观察到1 mM多巴胺与1 mM NO（2）（-），原位生成H（2）O（2）。在NO（2）（-）-，Fe（2 +）-或Fe（2 +）/ EDTA促进
• MONOMETHYLVALINE COMPOUNDS HAVING PHENYLALANINE SIDE-CHAIN MODIFICATIONS AT THE C-TERMINUS
  申请人：Seattle Genetics, Inc.

  公开号：US20130123465A1

  公开（公告）日：2013-05-16

  Auristatin peptide analogs of MeVal-Val-Dil-Dap-Phe (MMAF) are provided having C-terminal phenylalanine residue side chain replacements or modifications which are provided alone or attached to ligands through various linkers. The related conjugates can target specific cell types to provide therapeutic benefit.

  提供了MeVal-Val-Dil-Dap-Phe（MMAF）的Auristatin肽类类似物，其具有C-末端苯丙氨酸残基侧链替换或修饰，可单独提供或通过各种连接剂连接到配体上。相关的结合物可以定向特定的细胞类型，以提供治疗效益。
• Monomethylvaline compounds having phenylalanine side-chain modification at the C-terminus
  申请人：Seattle Genetics, Inc.

  公开号：US10000555B2

  公开（公告）日：2018-06-19

  Auristatin peptide analogs of MeVal-Val-Dil-Dap-Phe (MMAF) are provided having C-terminal phenylalanine residue side chain replacements or modifications which are provided alone or attached to ligands through various linkers. The related conjugates can target specific cell types to provide therapeutic benefit.

  提供的 MeVal-Val-Dil-Dap-Phe (MMAF) Auristatin 肽类似物具有 C 端苯丙氨酸残基侧链替换或修饰，可单独提供或通过各种连接体连接到配体上。相关共轭物可靶向特定细胞类型，提供治疗效果。
• Methods and compositions for treating cancer using P2RX2 inhibitors
  申请人：Flagship Pioneering Innovations V, Inc.

  公开号：US10457740B1

  公开（公告）日：2019-10-29

  The present invention provides methods for treating cancer using P2RX2 inhibitors, such as P2RX2 inhibitory antibodies, among others. The invention also features compositions containing P2RX2 inhibitors, methods of diagnosing patients with P2RX2-associated cancer, and methods of predicting the response of cancer in a subject to treatment with P2RX2 inhibitors.

  本发明提供了使用 P2RX2 抑制剂（如 P2RX2 抑制抗体等）治疗癌症的方法。本发明还包括含有 P2RX2 抑制剂的组合物、诊断 P2RX2 相关癌症患者的方法以及预测癌症对 P2RX2 抑制剂治疗的反应的方法。
• Methods for treating cancer using GRM8 inhibitors
  申请人：Flagship Pioneering Innovations V, Inc.

  公开号：US10683352B1

  公开（公告）日：2020-06-16

  The present invention provides methods for treating cancer using mGluR8 inhibitors, such as mGluR8 inhibitory antibodies and small molecules. The invention also features compositions containing mGluR8 inhibitors, methods of diagnosing patients with mGluR8-associated cancer, and methods of predicting the response of cancer in a subject to treatment with mGluR8 inhibitors.

  本发明提供了使用mGluR8抑制剂（如mGluR8抑制抗体和小分子）治疗癌症的方法。本发明还包括含有 mGluR8 抑制剂的组合物、诊断 mGluR8 相关癌症患者的方法以及预测癌症对 mGluR8 抑制剂治疗的反应的方法。