(+/-)-1-(furan-2-yl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline | 1207096-09-0

• 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-(furan-2-yl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline
• 英文别名: 1-(2-furyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline；1-(2'-Furanyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline；1-(furan-2-yl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline
• CAS: 1207096-09-0；3161-10-2
• 化学式: C₁₅H₁₇NO₃
• 分子量: 259.305
• InChiKey: CFVPUAGUXJMGOL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  43.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (+/-)-1-(furan-2-yl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline 、 甲基丙烯酰氯 在 三乙胺 作用下， 以 甲苯 为溶剂， 以76%的产率得到(8aSR,10RS,12aRS,12bRS)-2,3-dimethoxy-8a-methyl-5,9,10,12b-tetrahydro-6H-10,12a-epoxyisoindolo[1,2-a]isoquinolin-8(8aH)-one
  参考文献：
  名称：

  A new approach to construction of isoindolo[1,2-a]isoquinoline alkaloids Nuevamine, Jamtine, and Hirsutine via IMDAF reaction

  摘要：

  The interaction between 1-furyl-1,2,3,4-tetrahydroisoquinolines and Unsaturated acids derivatives (acryloyl, methacryloyl, and crotonoyl chloride, maleic and citraconic anhydride) was studied. It was shown that the reaction proceeds via amide formation and Subsequent intramolecular Diels-Alder reaction of the furan (IMDAF). The [4+2] cycloaddition proceeded under mild reaction conditions (25-80 degrees C) and afforded only the exo-adduct in a high yield. With this method, a new approach to the isoindolo[1,2-a]isoquinoline system, the basic structural element of alkaloids Jamtine, Hirsutine, and Nuevamine, is proposed. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2009.02.024
• 作为产物：
  描述：

  1-(2-furyl)-6,7-dimethoxy-3,4-dihydroisoquinoline 在 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 反应 1.0h， 生成 (+/-)-1-(furan-2-yl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline
  参考文献：
  名称：

  水性介质中简单的Noyori型催化剂对四氢异喹啉和β-咔啉生物碱的高度对映选择性

  摘要：

  增强银：报道了在水性条件下用于二氢异喹啉骨架的对映选择性转移氢化的非常方便的改进方案。可以使用未改性的Noyori配体，并且使用银添加剂可以大大提高催化剂的活性（参见方案）。该协议被用于非常短的生物碱（S）-甜菜碱和（S）-crispine的合成。

  DOI：

  10.1002/chem.200902289

文献信息

• Exploration of 2-((Pyridin-4-ylmethyl)amino)nicotinamide Derivatives as Potent Reversal Agents against P-Glycoprotein-Mediated Multidrug Resistance
  作者：Qianqian Qiu、Wei Shi、Zheng Li、Bo Zhang、Miaobo Pan、Jian Cui、Yuxuan Dai、Wenlong Huang、Hai Qian

  DOI：10.1021/acs.jmedchem.6b01879

  日期：2017.4.13

  broad spectrum of unrelated chemotherapeutic drugs in structure and function, leading to chemotherapy failure. A series of 2-((pyridin-4-ylmethyl)amino)nicotinamide derivatives as potent reversal agents against P-glycoprotein-mediated multidrug resistance (MDR) were designed and synthesized. The majority of target compounds displayed great reversal potency, especially 9n. In-depth studies demonstrated 9n

  ATP结合盒（ABC）转运蛋白的过表达，如ABCB1，通常称为P-糖蛋白（P-gp），在结构和功能上引发了广泛的无关化疗药物的主动流出，从而导致化疗失败。设计并合成了一系列2-（（吡啶-4-基甲基）氨基）烟酰胺衍生物，作为对抗P-糖蛋白介导的多药耐药性（MDR）的有效逆转剂。大多数目标化合物显示出很大的逆转能力，尤其是9n。深入研究表明，9n在逆转K562 / A02细胞中对阿霉素（ADM）的耐药性方面具有很高的效力（EC 50 = 119.6±6.9 nM），低细胞毒性和较长的持续时间（> 24小时）。9n还改善了与MDR相关的其他细胞毒性剂的作用，增加了ADM的积累，中断了P-gp介导的Rh123外排功能，并抑制了K562 / A02 MDR细胞中的P-gp ATPase活性。Western印迹分析表明MDR逆转9n不是由于蛋白质表达的降低。此外，CYP3A4的作用不受9n的影响，避免
• A Highly Enantioselective Access to Tetrahydroisoquinoline and β-Carboline Alkaloids with Simple Noyori-Type Catalysts in Aqueous Media
  作者：Laurent Evanno、Joel Ormala、Petri M. Pihko

  DOI：10.1002/chem.200902289

  日期：2009.12.7

  enhancement: A very convenient modified protocol for the enantioselective transfer hydrogenation of dihydroisoquinoline skeletons under aqueous conditions is reported. Unmodified Noyori ligands can be used and the activity of the catalyst is greatly enhanced with silver additives (see scheme). The protocol was used in a very short synthesis of the alkaloids (S)‐harmicine and (S)‐crispine.

  增强银：报道了在水性条件下用于二氢异喹啉骨架的对映选择性转移氢化的非常方便的改进方案。可以使用未改性的Noyori配体，并且使用银添加剂可以大大提高催化剂的活性（参见方案）。该协议被用于非常短的生物碱（S）-甜菜碱和（S）-crispine的合成。
• Selective GABA antagonists, especially isoquinoline derivatives, and their use for treating CNS disorders
  申请人：JOHN WYETH & BROTHER LIMITED

  公开号：EP0419247A2

  公开（公告）日：1991-03-27

  The invention concerns a new method for treating pain and/or CNS disorders using a compound which acts selectively as an antagonist f gamma aminobutyric acid (GABA) at GABA autoreceptors relative to GABAA receptors.

  本发明涉及一种使用一种化合物治疗疼痛和/或中枢神经系统疾病的新方法，该化合物相对于 GABAA 受体，在 GABA 自身受体上选择性地作为拮抗剂 f γ 氨基丁酸（GABA）。
• 1-Aryl-tetrahydroisoquinoline analogs as active anti-HIV agents in vitro
  作者：Pi Cheng、Ning Huang、Zhi-Yong Jiang、Quan Zhang、Yong-Tang Zheng、Ji-Jun Chen、Xue-Mei Zhang、Yun-Bao Ma

  DOI：10.1016/j.bmcl.2008.02.040

  日期：2008.4

  A series of 1-aryl-6,7-dihydroxyl(methoxy)-1,2,3,4-tetrahydroisoquinolines (compounds 1-36) were synthesized via Pictet-Spengler cyclization. All the synthesized compounds were assayed for activities against HIV-1(IIIB) in C8166 cell cultures by MTT method for the first time. The results of the anti-HIV screening revealed that 6,7-dihydroxytetrahydroisoquinolines possessed higher selective index than 6,7-dimethoxyl analogs due to the significantly decreased cytotoxicities. Compounds 6, 24, and 36 showed potent anti-HIV activities with EC50 values of 8.2, 4.6, and 5.3 mu M respectively, and the cytotoxicities (CC50) of these three compounds were 784.3, 727.3, and 687.3 mu M, which resulted in SI values larger than 95, 159, and 130 respectively. (C) 2008 Elsevier Ltd. All rights reserved.
• US5210088A
  申请人：——

  公开号：US5210088A

  公开（公告）日：1993-05-11