6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline-2-carboxamidine | 37519-72-5

• 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: 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline-2-carboxamidine
• 英文别名: 6,7-dimethoxy-3,4-dihydro-1H-isoquinoline-2-carboximidic acid amide；6,7-dimethoxy-3,4-dihydroisoquinoline-2(1H)-carboximidamide；6,7-dimethoxy-3,4-dihydro-1H-isoquinoline-2-carboximidamide
• CAS: 37519-72-5
• 化学式: C₁₂H₁₇N₃O₂
• mdl: MFCD11137444
• 分子量: 235.286
• InChiKey: NCPCJQGNKQRLNT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.416
• 拓扑面积：
  71.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  在 盐酸 作用下， 生成 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline-2-carboxamidine
  参考文献：
  名称：

  Expression in yeast, new substrates, and construction of a first 3D model of human orphan cytochrome P450 2U1: Interpretation of substrate hydroxylation regioselectivity from docking studies

  摘要：

  Background: Cytochrome P450 2U1 (CYP2U1) has been identified from the human genome and is highly conserved in the living kingdom. In humans, it has been found to be predominantly expressed in the thymus and in the brain. CYP2U1 is considered as an "orphan" enzyme as few data are available on its physiological function(s) and active site topology. Its only substrates reported so far were unsaturated fatty acids such as arachidonic acid, and, much more recently, N-arachidonoylserotonin.Methods: We expressed CYP2U1 in yeast Saccharomyces cerevisiae, built a 3D homology model of CYP2U1, screened a library of compounds known to be substrates of CYP2 family with metabolite detection by high performance liquid chromatography mass spectrometry, and performed docking experiments to explain the observed regioselectivity of the reactions.Results: We show that drug-related compounds, debrisoquine and terfenadine derivatives, subtrates of CYP2D6 and CYP2J2, are hydroxylated by recombinant CYP2U1 with regioselectivities different from those reported for CYP2D6 and 2J2. Docking experiments of those compounds and of arachidonic acid allow us to explain the regioselectivity of the hydroxylations on the basis of their interactions with key residues of CYP2U1 active site.Major conclusion: Our results show for the first time that human orphan CYP2U1 can oxidize several exogenous molecules including drugs, and describe a first CYP2U1 3D model.General significance: These results could have consequences for the metabolism of drugs particularly in the brain. The described 3D model should be useful to identify other substrates of CYP2U1 and help in understanding its physiologic roles. (C) 2015 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.bbagen.2015.03.014

文献信息

• [EN] BENZONAPHTHYRIDINES WITH PDE 3/4 INHIBITING ACTIVITY<br/>[FR] NOUVELLES BENZONAPHTYRIDINES
  申请人：ALTANA PHARMA AG

  公开号：WO2004018465A9

  公开（公告）日：2005-09-15

  [EN] Compounds of a certain formula (1), in which R1, R2, R3, R4 and R5 have the meanings indicated in the description, are novel effective PDE4 or PDE3/4 inhibitors.
  [FR] L'invention concerne des composés représentés par la formule générale (1) dans laquelle R1, R2, R3, R4 et R5 désignent des éléments décrits dans la partie descriptive de la présente demande. Ces composés sont de nouveaux inhibiteurs puissants de la PDE4 ou de la PDE3/4.
• [EN] NOVEL BENZONAPHTHYRIDINES<br/>[FR] NOUVELLES BENZONAPHTYRIDINES
  申请人：ALTANA PHARMA AG

  公开号：WO2004018465A2

  公开（公告）日：2004-03-04

  Compounds of a certain formula (1), in which R1, R2, R3, R4 and R5 have the meanings indicated in the description, are novel effective PDE4 or PDE3/4 inhibitors.