2-Methyl-1,2,3,4-tetrahydroisochinolin

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四氢异喹啉
• 英文名称: 2-Methyl-1,2,3,4-tetrahydroisochinolin
• 英文别名: 2-Methyl-1,2,3,4-tetrahydroisoquinolin-2-ium
• 化学式: C₁₀H₁₃N*H
• 分子量: 148.228
• InChiKey: KYXSVGVQGFPNRQ-UHFFFAOYSA-O

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  11
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  4.4
• 氢给体数：
  1
• 氢受体数：
  0

反应信息

• 作为产物：
  描述：

  2-甲基-1,2,3,4-四氢异喹啉 生成 2-Methyl-1,2,3,4-tetrahydroisochinolin
  参考文献：
  名称：

  J. CHROMATOGR. BIOMED. APPL., 533,(1990) C. 145-151

  摘要：

  DOI：

文献信息

• Sequence‐Based <i>In‐silico</i> Discovery, Characterisation, and Biocatalytic Application of a Set of Imine Reductases
  作者：Stefan Velikogne、Verena Resch、Carina Dertnig、Joerg H. Schrittwieser、Wolfgang Kroutil

  DOI：10.1002/cctc.201800607

  日期：2018.8.13

  of the IREDs with an alcohol dehydrogenase for cofactor regeneration led to whole‐cell biocatalysts capable of efficiently reducing imines at 100 mM initial concentration with no need for the addition of extracellular nicotinamide cofactor. Preparative biotransformations on gram scale using these ‘designer cells’ afforded chiral amines in good yield and excellent optical purity.

  亚胺还原酶（IRED）最近成为生物催化研究的主要焦点，补充了其他类别的胺形成酶，例如转氨酶和胺脱氢酶。跟随其他研究小组的脚步，我们通过基于序列的硅酶发现建立了一套 IRED 生物催化剂。在这项研究中，我们提供了这些新型 IRED 的基本表征数据，并使用一组结构多样的环状亚胺作为底物探索它们的活性和立体选择性。在许多情况下观察到>1 U/mg 的比活性和优异的立体选择性 ( ee >99%)，并且这些酶被证明对升高的底物负载具有令人惊讶的耐受性。IRED 与用于辅因子再生的乙醇脱氢酶的共表达导致全细胞生物催化剂能够在 100 mM 初始浓度下有效还原亚胺，而无需添加细胞外烟酰胺辅因子。使用这些“设计细胞”进行克级的制备性生物转化，以良好的产率和优异的光学纯度提供手性胺。
• A Rapid and Efficient Assay for the Characterization of Substrates and Inhibitors of Nicotinamide <i>N</i>-Methyltransferase
  作者：Matthijs J. van Haren、Javier Sastre Toraño、Davide Sartini、Monica Emanuelli、Richard B. Parsons、Nathaniel I. Martin

  DOI：10.1021/acs.biochem.6b00733

  日期：2016.9.20

  Nicotinamide N-methyltransferase (NNMT) is one of the most abundant small molecule methyltransferases in the human body and is primarily responsible for the N-methylation of the nicotinamide (vitamin B3). Employing the cofactor S-adenosyl-l-methionine, NNMT transfers a methyl group to the pyridine nitrogen of nicotinamide to generate N-methylnicotinamide. Interestingly, NNMT is also able to N-methylate a variety of other pyridine-containing small molecules, suggesting a secondary role for the enzyme in the detoxification of xenobiotics. A number of recent studies have also revealed links between NNMT overexpression and a variety of diseases, including multiple cancers, Parkinson’s disease, diabetes, and obesity. To facilitate further study of both the substrate scope and potential for inhibitor development, we here describe the development of a new NNMT activity assay. The assay makes use of ultra-high-performance hydrophilic interaction chromatography, allowing for rapid separation of the reaction products, coupled with quadrupole time-of-flight mass spectrometric detection, providing for enhanced sensitivity and enabling high-throughput sample analysis. We successfully demonstrated the general applicability of the method by performing kinetic analyses of NNMT-mediated methylation for a range of pyridine-based substrates. These findings also provide new insight into the diversity of substrate recognition by NNMT in a quantitative manner. In addition, we further established the suitability of the assay for the identification and characterization of small molecule inhibitors of NNMT. To do so, we investigated the inhibition of NNMT by the nonspecific methyltransferase inhibitors sinefungin and S-adenosyl-l-homocysteine, revealing IC50 values in the low micromolar range. The results of these inhibition studies are particularly noteworthy as they will permit future efforts toward the development of new NNMT-specific inhibitors.

  烟酰胺 N-甲基转移酶（NNMT）是人体内含量最多的小分子甲基转移酶之一，主要负责烟酰胺（维生素 B3）的 N-甲基化。利用辅助因子 S-腺苷-l-蛋氨酸，NNMT 将一个甲基转移到烟酰胺的吡啶氮上，生成 N-甲基烟酰胺。有趣的是，NNMT 还能对其他多种含吡啶的小分子进行 N 甲基化，这表明该酶在解毒异种生物方面起着辅助作用。最近的一些研究还揭示了 NNMT 过度表达与多种疾病（包括多种癌症、帕金森病、糖尿病和肥胖症）之间的联系。为了促进对底物范围和抑制剂开发潜力的进一步研究，我们在此介绍一种新型 NNMT 活性测定法的开发情况。该测定利用超高效亲水相互作用色谱法快速分离反应产物，并结合四极杆飞行时间质谱检测，提高了灵敏度，实现了高通量样品分析。通过对一系列基于吡啶的底物进行 NNMT 介导的甲基化动力学分析，我们成功证明了该方法的普遍适用性。这些发现也为定量了解 NNMT 识别底物的多样性提供了新的视角。此外，我们还进一步确定了该检测方法在鉴定和表征 NNMT 小分子抑制剂方面的适用性。为此，我们研究了非特异性甲基转移酶抑制剂松香菌素和 S-腺苷-l-高半胱氨酸对 NNMT 的抑制作用，结果显示 IC50 值在较低的微摩尔范围内。这些抑制研究的结果特别值得注意，因为它们将有助于今后开发新的 NNMT 特异性抑制剂。