1,2,3,4-tetrahydro-6,7-dimethoxy-3-Isoquinolinecarboxylic acid methyl ester | 57060-87-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 1,2,3,4-tetrahydro-6,7-dimethoxy-3-Isoquinolinecarboxylic acid methyl ester
• 英文别名: methyl 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylate；6,7-dimethoxy-1,2,3,4-tetrahydro-isoquinoline-3-carboxylic acid methyl ester；(E) 1,2,3,4-Tetrahydro-6,7-dimethoxy-3-isoquinolinecarboxylic acid, methylester；1,2,3,4-Tetrahydro-6,7-dimethoxy-3-isoquinolinecarboxylic acid,methylester
• CAS: 57060-87-4
• 化学式: C₁₃H₁₇NO₄
• 分子量: 251.282
• InChiKey: XAVYTZMVMTXAEC-UHFFFAOYSA-N

物化性质

• 熔点：
  210-214 °C(Solv: ethyl ether (60-29-7))
• 沸点：
  371.5±42.0 °C(Predicted)
• 密度：
  1.153±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  56.8
• 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-3-Isoquinolinecarboxylic acid methyl ester 在 N-甲基吗啉 、 水 、 1-羟基苯并三唑 、 sulfur 、 硝基苯 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 sodium hydroxide 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 31.0h， 生成 N,6,7-trimethoxy-N-methylisoquinoline-3-carboxamide
  参考文献：
  名称：

  [EN] COMPOSITIONS FOR THE TREATMENT OF BRAIN TUMORS
  [FR] COMPOSITIONS POUR LE TRAITEMENT DE TUMEURS CÉRÉBRALES

  摘要：

  这项即时发明描述了包括放射治疗和赛维特鲁内尔在内或不包括地塞米松的药物组合物和给药方案，以及治疗疾病、疾病或症状的方法。

  公开号：

  WO2020077197A1
• 作为产物：
  描述：

  methyl 2-(tert-butoxycarbonylamino)-3-(3,4-dimethoxyphenyl)propanoate 在 三氟乙酸 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 9.25h， 生成 1,2,3,4-tetrahydro-6,7-dimethoxy-3-Isoquinolinecarboxylic acid methyl ester
  参考文献：
  名称：

  Designing Nonsaccharide, Allosteric Activators of Antithrombin for Accelerated Inhibition of Factor Xa

  摘要：

  Antithrombin is a key regulator of coagulation and prime target of heparins, clinically used anticoagulants. Heparins induce a two-step conformational activation of antithrombin, a process that has remained challenging to target with molecules devoid of the antithrombin-binding pentasaccharide DEFGH. Computational screening of a focused library led to the design of two tetra-sulfated N-arylacyl tetrahydroisoquinoline variants as potential nonsaccharide activators of antithrombin. A high yielding synthetic scheme based on Horner-Wadsworth-Emmons or Pictet-Spengler reactions was developed to facilitate the functionalization of the tetrahydoisoquinoline ring, which upon further amidation, deprotection, and sulfation gave the targeted nonsaccharide activators. Spectrofluorometric measurement of affinity displayed antithrombin binding affinities in the low to high micromolar range at pH 6.0, I 0.05, 25 degrees C. Measurement of second-order rate constants of antithrombin inhibition of factor Xa in the presence and absence of the designed activators showed antithrombin activation in the range of 8-80-fold in the pH 6.0 buffer. This work puts forward 20c, a novel tetra-sulfated N-arylacyl tetrahydroisoquinoline-based molecule, that activates AT only 3.8-fold less than that achieved with DEFGH, suggesting a strong possibility of rationally designing sulfated organic molecules as clinically relevant AT activators.

  DOI：

  10.1021/jm2008387

文献信息

• Electronically rich N-substituted tetrahydroisoquinoline 3-carboxylic acid esters: concise synthesis and conformational studies
  作者：Rami A. Al-Horani、Umesh R. Desai

  DOI：10.1016/j.tet.2012.01.005

  日期：2012.2

  boxylic acid (THIQ3CA) scaffold is a key building block for a novel class of promising anticoagulants.10 The synthesis of THIQ3CA analogs, especially containing specific, electronically rich substituents, has been a challenge and essentially no efficient methods have been reported in the literature. We describe three complementary, glycine donor-based strategies for high yielding synthesis of highly

  我们实验室最近的工作表明，高度取代的、富含电子的 1,2,3,4-四氢异喹啉-3-羧酸 (THIQ3CA) 支架是一类新型抗凝剂的关键组成部分。10 THIQ3CA 类似物的合成，尤其是含有特定的、富含电子的取代基，一直是一个挑战，文献中基本上没有报道有效的方法。我们描述了三种互补的、基于甘氨酸供体的策略，用于高产合成高度取代的、富含电子的 THIQ3CA 酯。本文研究的三个甘氨酸供体包括乙内酰脲1、(±)-Boc-α-膦酰甘氨酸三甲酯2和 (±) -Z -α-膦酰甘氨酸三甲酯3. 虽然可以使用这三种中的任何一种来合成 THIQ3CA 类似物，但在三个温和、有效的步骤中使用3 可以最好地实现所需的 THIQ3CA 酯的最佳、高产率方法。使用这种方法，合成了先进的N-芳基酰基、N-芳基烷基和双-THIQ3CA 类似物的重点库。变温和溶剂依赖性 NMR 化学位移研究表明，N-芳基酰基-THIQ3CA
• [EN] COMPOSITIONS FOR THE TREATMENT OF BRAIN TUMORS<br/>[FR] COMPOSITIONS DESTINÉES AU TRAITEMENT DE TUMEURS CÉRÉBRALES
  申请人：INNOCRIN PHARMACEUTICALS INC

  公开号：WO2019182743A1

  公开（公告）日：2019-09-26

  The instant invention describes pharmaceutical compositions and dosing regimens comprising seviteronel and/or dexamethasone, and methods of treating diseases, disorders symptoms thereof.

  这项即时发明描述了包含赛维特龙和/或地塞米松的药物组合物和给药方案，以及治疗疾病、疾病症状的方法。
• Pd/C-Catalyzed Dehydrogenative [3+2] Cycloaddition for the Synthesis of Functionalized Tropanes
  作者：Hai-Jun Wang、Lei Guo、Cheng-Feng Zhu、Yun-Fei Luo、You-Gui Li、Xiang Wu

  DOI：10.1002/ejoc.201801147

  日期：2018.10.24

  Described is a Pd/C‐catalyzed dehydrogenative [3+2] cycloaddition for the synthesis of benzo‐fused tropanes. The reaction proceeds through a sequential Pd/C‐catalyzed dehydrogenative formation of azomethine ylides from amines and 1,3‐dipolar cycloaddition.

  描述了Pd / C催化的脱氢[3 + 2]环加成反应，用于合成苯并熔合的托烷。该反应通过胺的1,3-偶极环加成反应依次进行Pd / C催化的偶氮甲亚胺脱氢反应形成。
• 2-oxo-1-[[(substituted sulfonyl)amino]-carbonyl]azetidines
  申请人：E. R. Squibb & Sons, Inc.

  公开号：US04777252A1

  公开（公告）日：1988-10-11

  Antibacterial activity is exhibited by 3-acylamino-2-oxoazetidines having in the 1-position an activating group of the formula ##STR1## wherein R is ##STR2## and R.sub.4 is ##STR3##

  3-酰氨基-2-氧代杂环丁烷具有抗菌活性，在1-位置带有如下式中的活化基团##STR1##其中R为##STR2##，R.sub.4为##STR3##
• Derivatives of 8-epiblechnic Acid and their Effects on Down-Regulation of Endothelin (ETA) receptor mRNA
  申请人：Chan Hardy

  公开号：US20100048618A1

  公开（公告）日：2010-02-25

  The present application discloses derivatives of 8-epiblechnic acid and use thereof in treating a disease related to endothelin receptor A or endothelin-1 (ET-1) over-expression, such as hypertension, cancer, atherosclerosis, and myocardial infarction.

  本申请公开了8-epiblechnic酸的衍生物及其在治疗与内皮素受体A或内皮素-1（ET-1）过度表达相关的疾病中的应用，例如高血压，癌症，动脉粥样硬化和心肌梗死。