1,2,3,4-tetrahydro-6,7-dimethoxy-1<2-(3,4-dimethoxyphenyl)ethyl>isoquinoline | 65899-28-7

• 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: 1,2,3,4-tetrahydro-6,7-dimethoxy-1<2-(3,4-dimethoxyphenyl)ethyl>isoquinoline
• 英文别名: (+/-)-6,7-dimethoxy-1-[2-(3,4-dimethoxyphenyl)ethyl]-1,2,3,4-tetrahydroisoquinoline；1-(3,4-dimethoxyphenethyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline；1-[2-(3,4-dimethoxyphenyl)ethyl]-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline；1-(3,4-Dimethoxyphenethyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisochinolin；6,7-Dimethoxy-1-[2-(3,4-dimethoxyphenyl)ethyl]-1,2,3,4-tetrahydroisoquinoline
• CAS: 65899-28-7
• 化学式: C₂₁H₂₇NO₄
• 分子量: 357.45
• InChiKey: MZMBEDUFQKANOF-UHFFFAOYSA-N

物化性质

• 沸点：
  491.2±45.0 °C(Predicted)
• 密度：
  1.094±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  49
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1,2,3,4-tetrahydro-6,7-dimethoxy-1<2-(3,4-dimethoxyphenyl)ethyl>isoquinoline 以 乙腈 、 苯 为溶剂， 反应 96.0h， 生成 mono(2,2'-((pentane-1,5-diylbis(oxy))bis(3-oxopropane-3,1-diyl))bis(1-(3,4-dimethoxyphenethyl)-6,7-dimethoxy-2-methyl-1,2,3,4-tetrahydroisoquinolin-2-ium)) monomethanesulfonate
  参考文献：
  名称：

  Stenlake; Waigh; Dewar, European Journal of Medicinal Chemistry, 1981, vol. 16, # 6, p. 515 - 524

  摘要：

  DOI：
• 作为产物：
  描述：

  3,4-二甲氧基苯丙酸 在 sodium tetrahydroborate 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 、 三氯氧磷 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 2.0h， 生成 1,2,3,4-tetrahydro-6,7-dimethoxy-1<2-(3,4-dimethoxyphenyl)ethyl>isoquinoline
  参考文献：
  名称：

  Effect of 1-Substitution on Tetrahydroisoquinolines as Selective Antagonists for the Orexin-1 Receptor

  摘要：

  Selective blockade of the orexin-1 receptor (OX1) has been suggested as a potential approach to drug addiction therapy because of its role in modulating the brain's reward system. We have recently reported a series of tetrahydroisoquinoline-based OX1 selective antagonists. Aimed at elucidating structure-activity relationship requirements in other regions of the molecule and further enhancing OX1 potency and selectivity, we have designed and synthesized a series of analogues bearing a variety of substituents at the 1-position of the tetrahydroisoquinoline. The results show that an optimally substituted benzyl group is required for activity at the OX1 receptor. Several compounds with improved potency and/or selectivity have been identified. When combined with structural modifications that were previously found to improve selectivity, we have identified compound 73 (RTIOX-251) with an apparent dissociation constant (K-e) of 16.1 nM at the OX1 receptor and >620-fold selectivity over the OX2 receptor. In vivo, compound 73 was shown to block the development of locomotor sensitization to cocaine in rats.

  DOI：

  10.1021/cn500330v

文献信息

• ANTI-HIV COMPOUNDS
  申请人：Prosetta Antiviral, Inc.

  公开号：US20160168100A1

  公开（公告）日：2016-06-16

  This invention provides, among other things, tetrahydroisoquinolines useful for treating viral infections, pharmaceutical formulations containing such compounds, as well as methods of inhibiting the replication of a virus, such as HIV, or treating a disease, such as AIDS.

  这项发明提供了用于治疗病毒感染的四氢异喹啉等化合物，含有这类化合物的药物配方，以及抑制病毒（如HIV）复制或治疗疾病（如艾滋病）的方法。
• [EN] TETRAHYDROISOQUINOLYL ACETAMIDE DERIVATIVES FOR USE AS OREXIN RECEPTOR ANTAGONISTS<br/>[FR] DERIVES DE TETRAHYDRO-ISOQUINOLYL-ACETAMIDE DESTINES A SERVIR D'ANTAGONISTES DES RECEPTEURS D'OREXINE
  申请人：ACTELION PHARMACEUTICALS LTD

  公开号：WO2004085403A1

  公开（公告）日：2004-10-07

  The invention relates to novel acetamide derivatives of formula (I) and their use as active ingredients in the preparation of pharmaceutical compositions. The invention also concerns related aspects including processes for the preparation of such compounds, pharmaceutical compositions containing one or more of those compounds and especially their use as orexin receptor antagonists.

  该发明涉及公式（I）的新型乙酰胺衍生物及其在制备药物组合物中作为活性成分的用途。该发明还涉及相关方面，包括制备这类化合物的方法、含有其中一个或多个这类化合物的药物组合物，特别是它们作为促进睡眠的药物受体拮抗剂的用途。
• Pyridine, pyrimidine, quinoline, quinazoline, and naphthalene urotensin-II receptor antagonists
  申请人：Wu Chengde

  公开号：US20050054850A1

  公开（公告）日：2005-03-10

  The present invention relates to urotensin II receptor antagonists, pharmaceutical compositions containing them and their use.

  本发明涉及尿苷II受体拮抗剂，含有它们的药物组合物以及它们的用途。
• An Easy-To-Use, Regioselective, and Robust Bis(amidate) Titanium Hydroamination Precatalyst: Mechanistic and Synthetic Investigations toward the Preparation of Tetrahydroisoquinolines and Benzoquinolizine Alkaloids
  作者：Zhe Zhang、David C. Leitch、Man Lu、Brian O. Patrick、Laurel L. Schafer

  DOI：10.1002/chem.200600735

  日期：2007.2.23

  Amidate-supported titanium amido complexes are efficient and regioselective precatalysts for intermolecular hydroamination of terminal alkynes with primary amines. The synthesis and characterization of the first bis(amidate)-supported titanium-imido complex is reported. Its role as the active catalytic species is suggested in the course of product distribution studies using deuterated substrates. The bis(amidate)-supported

  酰胺化物支持的钛酰胺基络合物是用于末端炔烃与伯胺的分子间加氢胺化的有效和区域选择性的预催化剂。报道了第一双（氨基甲酸酯）负载的钛-亚氨基配合物的合成和表征。在使用氘代底物的产品分布研究过程中建议了其作为活性催化物质的作用。双（氨基甲酸酯）负载的预催化剂表现出良好的官能团耐受性，甚至在存在酯基和酰胺基的情况下进行加氢胺化反应。在合成多种1-取代的四氢异喹啉碱类生物碱和一锅加氢胺化程序中，利用该官能团耐受性可高产制备苯并[a]喹啉嗪骨架。
• Unified Approach to Isoindolinones and THIQs via Lewis Acid Catalyzed Domino Mukaiyama–Mannich Lactamization/Alkylations: Application in the Synthesis of (±)-Homolaudanosine
  作者：Sivasankaran Dhanasekaran、Anirban Kayet、Arun Suneja、Vishnumaya Bisai、Vinod K. Singh

  DOI：10.1021/acs.orglett.5b01197

  日期：2015.6.5

  variety of isoindolinones and tetrahydroisoquinolines via a Lewis acid catalyzed domino Mukaiyama–Mannich lactamization/alkylation is achieved. This transformation comprises a sequential formation of three new bonds through a one-pot, three-component procedure to afford product in moderate to high yields. A concise synthesis of (±)-homolaudanosine (2b) has been achieved using this method.

  通过路易斯酸催化的多米诺山Mukaiyama–Mannich内酰胺化/烷基化反应，可以实现新颖而有效的多种异吲哚啉酮和四氢异喹啉的合成。这种转变包括通过一锅三组分程序依次形成三个新的键，以提供中等至高收率的产物。使用此方法已实现了（±）-高麦芽糖苷（2b）的简明合成。