3-(6,7-dimethoxy-3, 4-dihydroisoquinolin-2(1H)-yl) propan-1-ol

• 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: 3-(6,7-dimethoxy-3, 4-dihydroisoquinolin-2(1H)-yl) propan-1-ol
• 英文别名: 3-(6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline-2-yl)propan-1-ol；2-<γ-Hydroxy-propyl>-6,7-dimethoxy-1,2,3,4-tetrahydro-isochinolin；3-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)-propan-1-ol；3-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)propan-1-ol
• 化学式: C₁₄H₂₁NO₃
• mdl: MFCD11613844
• 分子量: 251.326
• InChiKey: FRZFXAJJOUAIJV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.571
• 拓扑面积：
  41.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(6,7-dimethoxy-3, 4-dihydroisoquinolin-2(1H)-yl) propan-1-ol 在 sodium hydride 、 三乙胺 作用下， 以 二氯甲烷 、 甲苯 、 mineral oil 为溶剂， 反应 1.0h， 生成 2-[3-[6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl]propyl]-3,4-dihydroisoquinolin-1(2H)-one
  参考文献：
  名称：

  Arylamides hybrids of two high-affinity σ2 receptor ligands as tools for the development of PET radiotracers

  摘要：

  1-Cyclohexy1-4-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)propyl]piperazine 1 (PB28) and 2-Methoxy-5-methyl-N-[4-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)butyl]benzamide 2 (RHM-1) represent leads for tumor diagnosis, given their high affinity at sigma(2) receptors. With the purpose of obtaining good candidates for sigma(2) PET tracers development, hybrid structures between 1 and 2 were designed. Excellent sigma(1)/sigma(2) selectivities were reached when 6,7-dimethoxytetrahydroisoquinoline was linked to an o-methoxy substituted arylamide (11a, 12a, 15a). and for these benzamides an intramolecular H-bond in the active conformation at the sigma sites, was hypothesized. However these excellent sigma(2) ligands were accompanied by interaction with P-gp. which may limit their use as sigma(2) receptor PET agents when tumors overexpress P-gp. Compound 15a whose P-gp interaction was just moderate represents an interesting tool for the development of sigma(2) PET tracers useful in tumors overexpressing P-gp. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.05.057
• 作为产物：
  描述：

  3,4-二甲氧基苯乙胺 在 potassium carbonate 、 sodium iodide 作用下， 以 甲酸 、 N,N-二甲基甲酰胺 为溶剂， 反应 28.0h， 生成 3-(6,7-dimethoxy-3, 4-dihydroisoquinolin-2(1H)-yl) propan-1-ol
  参考文献：
  名称：

  New efficient imidazolium aldoxime reactivators for nerve agent-inhibited acetylcholinesterase

  摘要：

  Herein, we described a new class of uncharged non-pyridinium reactivators for nerve agent-inhibited acetylcholinesterase (AChE). Based on a dual site binding strategy, we conjugated the imidazolium aldoxime to different peripheral site ligands (PSLs) of AChE through alkyl chains. Compared with the known quaternary pyridinium reactivators, two of the resulting conjugates (7g and 7h) were highlighted to be the first efficient non-pyridinium oxime conjugates exhibiting similar or superior ability to reactivate sarin-, VX- and tabun-inhibited AChE. Moreover, they were more broad-spectrum reactivators. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.10.055

文献信息

• Synthesis of a P-Glycoprotein Inhibitor and Its High-Energy (<i>Z</i>)-Isomer by Carbenoid Eliminative Cross-Coupling
  作者：Subhash D. Tanpure、Mohamed F. El-Mansy、Paul R. Blakemore

  DOI：10.1021/acs.orglett.0c00755

  日期：2020.4.17

  To gauge the feasibility of carbenoid eliminative cross-coupling for the synthesis of polyfunctional alkenes, a P-glycoprotein inhibitor containing an (E)-configured 4-chromanylidene-type trisubstituted olefin was prepared as well as its previously undescribed (Z)-isomer. Stereospecific alkene synthesis required generation of functionalized enantioenriched α-metalated carbamates [R1R2CM(O2CNi-Pr2)

  为了评估类胡萝卜素消除交叉偶联用于合成多官能烯烃的可行性，制备了包含（E）-构型的4-苯并二氢萘基型三取代烯烃的P-糖蛋白抑制剂及其先前未描述的（Z）-异构体。立体定向烯烃的合成需要生成功能化的对映体富集的α-金属氨基甲酸酯[R 1 R 2 CM（O 2 CN i -Pr 2），M = Li或Bneo]，并且遇到了与不正确的锂化区域选择性和意外的有机锂构型不稳定性相关的问题。描述了解决这些难题的方法，以及用于ee测定α-氨基甲酰氧基硼酸酯的方法。
• SAR Studies on Tetrahydroisoquinoline Derivatives: The Role of Flexibility and Bioisosterism To Raise Potency and Selectivity toward P-glycoprotein
  作者：Elena Capparelli、Laura Zinzi、Mariangela Cantore、Marialessandra Contino、Maria Grazia Perrone、Gert Luurtsema、Francesco Berardi、Roberto Perrone、Nicola A. Colabufo

  DOI：10.1021/jm501640e

  日期：2014.12.11

  The development of P-glycoprotein (P-gp) ligands remains of considerable interest, mostly for investigating the protein's structure and transport mechanism. In recent years, many different generations of ligands have been tested for their ability to modulate P-gp activity. The aim of the present work is to perform SAR studies on tetrahydroisoquinoline derivatives in order to design potent and selective P-gp ligands. For this purpose, the effect of bioisosteric replacement and the role of flexibility have been investigated, and four series of tetrahydroisoquinoline ligands have been developed: (a) 2-aryloxazole bioisosteres, (b) elongated analogues, (c) 2H-chromene, and (d) 2-biphenyl derivatives. The results showed that both 2-biphenyl derivative 20b and elongated derivative 6g behaved as strong P-gp substrates. In conclusion, important aspects for developing potent and selective P-gp ligands have been highlighted, providing a solid starting point for further optimization.
• Synthesis, electrophysiological properties and analysis of structural requirements of a novel class of antiarrhythmic agents with potassium and calcium channel blocking properties
  作者：Guy Nadler、Jean-François Faivre、Marie-Claire Forest、Brigitte Cheval、Michel Martin、Michel Souchet、Bernard Gout、Antoine Bril

  DOI：10.1016/s0968-0896(98)00166-7

  日期：1998.11

  Class III antiarrhythmic agents have been shown to prevent reentrant arrhythmias but also to be responsible for initiating arrhythmias characterised by afterdepolarizations and triggered activities. By combining potassium and calcium channel antagonistic actions, as with BRL-32872(1,2) (1), it might be possible to reduce the incidence of proarrhythmias albeit retaining antiarrhythmic efficacy. In the present study we synthesised and tested for their electrophysiological activity in guinea pig papillary muscle a wide panel of analogues of BRL-32872. Some qualitative relationships between compound structure and the inhibitory effect on the rapidly activating component of the delayed rectifier potassium current and/or the L-type calcium current will be presented. New derivatives depicting bell-shaped dose-response curves on action potential duration may therefore represent novel agents for improved antiarrhythmic therapy. (C) 1998 Elsevier Science Ltd. All rights reserved.
• Arylamides hybrids of two high-affinity σ2 receptor ligands as tools for the development of PET radiotracers
  作者：Carmen Abate、Savina Ferorelli、Marialessandra Contino、Roberta Marottoli、Nicola Antonio Colabufo、Roberto Perrone、Francesco Berardi

  DOI：10.1016/j.ejmech.2011.05.057

  日期：2011.9

  1-Cyclohexy1-4-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)propyl]piperazine 1 (PB28) and 2-Methoxy-5-methyl-N-[4-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)butyl]benzamide 2 (RHM-1) represent leads for tumor diagnosis, given their high affinity at sigma(2) receptors. With the purpose of obtaining good candidates for sigma(2) PET tracers development, hybrid structures between 1 and 2 were designed. Excellent sigma(1)/sigma(2) selectivities were reached when 6,7-dimethoxytetrahydroisoquinoline was linked to an o-methoxy substituted arylamide (11a, 12a, 15a). and for these benzamides an intramolecular H-bond in the active conformation at the sigma sites, was hypothesized. However these excellent sigma(2) ligands were accompanied by interaction with P-gp. which may limit their use as sigma(2) receptor PET agents when tumors overexpress P-gp. Compound 15a whose P-gp interaction was just moderate represents an interesting tool for the development of sigma(2) PET tracers useful in tumors overexpressing P-gp. (C) 2011 Elsevier Masson SAS. All rights reserved.
• New efficient imidazolium aldoxime reactivators for nerve agent-inhibited acetylcholinesterase
  作者：Zhao Wei、Yan-qin Liu、Xin-bo Zhou、Yuan Luo、Chun-qian Huang、Yong-an Wang、Zhi-bing Zheng、Song Li

  DOI：10.1016/j.bmcl.2014.10.055

  日期：2014.12

  Herein, we described a new class of uncharged non-pyridinium reactivators for nerve agent-inhibited acetylcholinesterase (AChE). Based on a dual site binding strategy, we conjugated the imidazolium aldoxime to different peripheral site ligands (PSLs) of AChE through alkyl chains. Compared with the known quaternary pyridinium reactivators, two of the resulting conjugates (7g and 7h) were highlighted to be the first efficient non-pyridinium oxime conjugates exhibiting similar or superior ability to reactivate sarin-, VX- and tabun-inhibited AChE. Moreover, they were more broad-spectrum reactivators. (C) 2014 Elsevier Ltd. All rights reserved.