7-甲氧基-2-[2-(4-甲氧基苯基)乙基]-1,2,3,4-四氢异喹啉-6-醇 | 1064198-55-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四氢异喹啉
• 中文名称: 7-甲氧基-2-[2-(4-甲氧基苯基)乙基]-1,2,3,4-四氢异喹啉-6-醇
• 英文名称: 7-methoxy-2-[2-(4-methoxyphenyl)ethyl]-1,2,3,4-tetrahydroisoquinolin-6-ol
• 英文别名: 6-hydroxy-7-methoxy-2-(4-methoxyphenethyl)-1,2,3,4-tetrahydroisoquinoline；7-methoxy-2-[2-(4-methoxyphenyl)ethyl]-3,4-dihydro-1H-isoquinolin-6-ol
• CAS: 1064198-55-5
• 化学式: C₁₉H₂₃NO₃
• 分子量: 313.397
• InChiKey: CAJPVOODRJHZQU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  41.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  3-羟基-4-甲氧基苯乙酸 在 盐酸 、 三乙胺 、 三氯氧磷 作用下， 以 甲醇 、 5,5-dimethyl-1,3-cyclohexadiene 、 二氯甲烷 、 水 、 甲苯 为溶剂， 反应 26.5h， 生成 7-甲氧基-2-[2-(4-甲氧基苯基)乙基]-1,2,3,4-四氢异喹啉-6-醇
  参考文献：
  名称：

  A New Class of Selective and Potent 7-Dehydrocholesterol Reductase Inhibitors

  摘要：

  We prepared a number of N-phenethyltetrahydroisoquinolines structurally related to protoberberines. They were tested for activity against bacteria, fungi, and human leukemia HL-60 cells and also for inhibition of biosynthesis: ergosterol in yeasts and cholesterol in human cells. In the latter assay panel, several of the compounds were distinguished by a strong and selective inhibition of 7-dehydrocholesterol reductase (7-DHCR, EC 1.3.1.21), an enzyme responsible for the conversion of 7-dehydrocholesterol to cholesterol in the last step of cholesterol biosynthesis. In a whole-cell assay, the most active compound 5f showed a much stronger inhibition of overall cholesterol biosynthesis (IC50 2.3 nM) than BM 15.766 (IC50 500 nM), presently the most selective known inhibitor of 7-DHCR Since a defect of 7-dehydrocholesterol reductase is associated with Smith-Lemli-Opitz syndrome (SLOS), the potent and selective inhibitors reported here will enable more detailed investigation of the pathogenesis of SLOS.

  DOI：

  10.1021/jm3006096

文献信息

• COMPOUND
  申请人：Jourdan Fabrice

  公开号：US20100222299A1

  公开（公告）日：2010-09-02

  The present invention involves tetrahydroisoquinoline compounds and their use in the inhibition and/or prevention of tumor growth.

  本发明涉及四氢异喹啉化合物及其在抑制和/或预防肿瘤生长中的应用。
• TETRAHYDROISOQUINOLINES AS TUMOUR GROWTH INHIBITORS
  申请人：Sterix Limited

  公开号：EP2155192A2

  公开（公告）日：2010-02-24
• US8394825B2
  申请人：——

  公开号：US8394825B2

  公开（公告）日：2013-03-12
• [EN] COMPOUND<br/>[FR] COMPOSÉ
  申请人：STERIX LTD

  公开号：WO2008117061A2

  公开（公告）日：2008-10-02

  [EN] The present invention provides a compound of Formula (I) or Formula (Il) wherein A is selected from CR₁₀R₁₁, -S(=O)₂-, -NR₁₂-,and C=O, wherein R₁₀ and R₁₁ independently selected from H, -OH, hydrocarbyl, -CN, -NO₂, and halogens, R₁₂ is selected from H and hydrocarbyl; B is selected from (CR₁₃R₁₄)_1-3, C=O, CR₁₅R₁₆C=O, -S(=O)₂-, -NR₁₇- and -NR₁₈-C(=O)-, wherein each of R₁₃, R₁₄, R₁₅ and R₁₆ is independently selected from H, -OH, hydrocarbyl, -CN, -NO₂, and halogens, R₁₇ and R₁₈ are independently selected from H and hydrocarbyl; R₁ is selected from OH, O-hydrocarbyl, O-heterohydrocarbyl, -SO₂-hydrocarbyl, -CH=CH₂, halogen, -OSO₂NR₁₉R₂₀, -C(=O)-NR₂₁R₂₂, -NR₂₃-C(=O)H and -NR₃₅R₃₆; wherein each of R₁₉, R₂₀, R₂₁, R₂₂, R₂₃, R₃₅ and R₃₆ is independently is selected from H and hydrocarbyl; R₂ is selected from H, -O-hydrocarbyl, -S-hydrocarbyl, hydrocarbyl, -CN, -NO₂, and halogens, R₃ is selected from Formula (A), Formula (B), Formula (C), Formula (D) wherein each of R₄, R₅, R₆, R₇ and R₈ is independently selected from H, -OH, hydrocarbyl, -O-hydrocarbyl, -COOH or an ester thereof, halocarbyl, -O-halocarbyl, acyl, -O-acyl, -NR₂₉-acyl, -O-SO₂NR₁₉R₂₀, -NR₃₀R₃₁, -NR₃₂SO₂R₃₃, -CN, -NO₂, and halogens, R₉ is selected from H and hydrocarbyl, and each R₂₉ to R₃₃ is independently selected from H and hydrocarbyl; and wherein two or more of R₄, R₅, R₆, R₇, R₈ and R₉ may together form a ring; wherein when R₁ is OH and R₃ is of Formula (D), (i) at least one of R₄, R₅, R₆, R₇ and R₈ is independently selected from halocarbyl, -O-halocarbyl, -O-acyl, -NR₂₉-acyl, -O- SO₂NR₁₉R₂₀, -NR₃₀R₃₁, -NR₃₂SO₂R₃₃, -CN, and halogens, or (ii) two or more of R₄, R₅, R₆, R₇ and R₈ together form a ring, or (iii) at least three of R₄, R₅, R₆, R₇ and R₈ are independently selected from -OH, hydrocarbyl, -O-hydrocarbyl, halocarbyl, -O-halocarbyl, -O-acyl, -NR₂₉-acyl, -O-SO₂NR₁₉R₂₀, -NR₃₀R₃₁, -NR₃₂SO₂R₃₃, -CN, -NO₂, and halogens; wherein h is an optional bond, wherein G is CR₂₄R₂₅, wherein R₂₄ and R₂₅ independently selected from H, -OH, hydrocarbyl, -CN, -NO₂, and halogens, or wherein when h is present G is CR₂₄, wherein R₂₄ is selected from H, -OH, hydrocarbyl, -CN, -NO₂, and halogens; n is 0, 1 or 2, each D is independently selected from O, NR₂₆ and CR₂₇R₂₈, wherein each R₂₆ is independently selected from H and hydrocarbyl; and each R₂₇ and R₂₈ is independently selected from H, -OH, hydrocarbyl, -CN, -NO₂, and halogens.
  [FR] La présente invention concerne un composé de formule (I) ou de formule (II) dans lesquelles A est choisi parmi CR₁₀R₁₁, -S(=O)₂-, -NR₁₂-, et C=O, R₁₀ et R₁₁ étant indépendamment choisis parmi H, -OH, un groupe hydrocarbyle, -CN, -NO₂, et des atomes d'halogène, et R₁₂ étant choisi parmi H et un groupe hydrocarbyle; B est choisi parmi (CR₁₃R₁₄)_1-3, C=0, CR₁₅R₁₆C=O, -S(=O)₂-, -NR₁₇- et -NR₁₈-C(=O)-, chacun de R₁₃, R₁₄, R₁₅ et R₁₆ étant indépendamment choisi parmi H, -OH, un groupe hydrocarbyle, -CN, -NO₂, et des atomes d'halogène, R₁₇
• A New Class of Selective and Potent 7-Dehydrocholesterol Reductase Inhibitors
  作者：Aline Horling、Christoph Müller、Richard Barthel、Franz Bracher、Peter Imming

  DOI：10.1021/jm3006096

  日期：2012.9.13

  We prepared a number of N-phenethyltetrahydroisoquinolines structurally related to protoberberines. They were tested for activity against bacteria, fungi, and human leukemia HL-60 cells and also for inhibition of biosynthesis: ergosterol in yeasts and cholesterol in human cells. In the latter assay panel, several of the compounds were distinguished by a strong and selective inhibition of 7-dehydrocholesterol reductase (7-DHCR, EC 1.3.1.21), an enzyme responsible for the conversion of 7-dehydrocholesterol to cholesterol in the last step of cholesterol biosynthesis. In a whole-cell assay, the most active compound 5f showed a much stronger inhibition of overall cholesterol biosynthesis (IC50 2.3 nM) than BM 15.766 (IC50 500 nM), presently the most selective known inhibitor of 7-DHCR Since a defect of 7-dehydrocholesterol reductase is associated with Smith-Lemli-Opitz syndrome (SLOS), the potent and selective inhibitors reported here will enable more detailed investigation of the pathogenesis of SLOS.