(5-methoxy-1,2,3,4-tetrahydroisoquinolin-1-yl)acetic acid ethyl ester | 1424-92-6

• 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: (5-methoxy-1,2,3,4-tetrahydroisoquinolin-1-yl)acetic acid ethyl ester
• 英文别名: ethyl 2-(5-methoxy-1,2,3,4-tetrahydroisoquinolin-1-yl)acetate；1,2,3,4-Tetrahydro-5-methoxy-isochinolin-1-yl>essigsaeure-ethylester
• CAS: 1424-92-6
• 化学式: C₁₄H₁₉NO₃
• 分子量: 249.31
• InChiKey: NODXTQZKFBDERX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.84
• 重原子数：
  18.0
• 可旋转键数：
  4.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  47.56
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  (5-methoxy-1,2,3,4-tetrahydroisoquinolin-1-yl)acetic acid ethyl ester 在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 以111 mg的产率得到1-Isoquinolineacetic acid,1,2,3,4-tetrahydro-5-hydroxy-,ethyl ester
  参考文献：
  名称：

  A conformational restriction approach to the development of dual inhibitors of acetylcholinesterase and serotonin transporter as potential agents for Alzheimer's disease

  摘要：

  Alzheimer's disease (AD) has been treated with acetylcholinesterase (AChE) inhibitors such as donepezil. However, the clinical usefulness of AChE inhibitors is limited mainly due to their adverse peripheral effects. Depression seen in AD patients has been treated with serotonin transporter (SERT) inhibitors. We considered that combining SERT and AChE inhibition could improve the clinical usefulness of AChE inhibitors. In a previous paper, we found a potential dual inhibitor, 1, of AChE (IC50 = 101 nM) and SERT (IC50 = 42 nM), but its AChE inhibition activity was less than donepezil (IC50 = 10 nM). Here, we report the conformationally restricted (R)-18a considerably enhanced inhibitory activity against AChE (IC50 14 nM) and SERT (IC50 = 6 nM). (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(03)00452-8
• 作为产物：
  描述：

  1-carbethoxymethylene-5-methoxy-1,2,3,4-tetrahydroisoquinoline 在 platinum(IV) oxide 氢气 、 溶剂黄146 作用下， 生成 (5-methoxy-1,2,3,4-tetrahydroisoquinolin-1-yl)acetic acid ethyl ester
  参考文献：
  名称：

  A conformational restriction approach to the development of dual inhibitors of acetylcholinesterase and serotonin transporter as potential agents for Alzheimer's disease

  摘要：

  Alzheimer's disease (AD) has been treated with acetylcholinesterase (AChE) inhibitors such as donepezil. However, the clinical usefulness of AChE inhibitors is limited mainly due to their adverse peripheral effects. Depression seen in AD patients has been treated with serotonin transporter (SERT) inhibitors. We considered that combining SERT and AChE inhibition could improve the clinical usefulness of AChE inhibitors. In a previous paper, we found a potential dual inhibitor, 1, of AChE (IC50 = 101 nM) and SERT (IC50 = 42 nM), but its AChE inhibition activity was less than donepezil (IC50 = 10 nM). Here, we report the conformationally restricted (R)-18a considerably enhanced inhibitory activity against AChE (IC50 14 nM) and SERT (IC50 = 6 nM). (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(03)00452-8

文献信息

• 一种构建四氢异喹啉类化合物的方法
  申请人：中国科学院福建物质结构研究所

  公开号：CN110452169B

  公开（公告）日：2021-02-19

  本申请公开了一种化合物，具有式I所示的结构式。以及该化合物的制备方法，该方法利用氨基导向的苯乙胺邻位C(sp2)–H键烯基化环化反应，从而获得了高效合成四氢异喹啉类化合物的方法。
• Palladium-Catalyzed C(sp²)–H Olefination of Free Primary and Secondary 2-Phenylethylamines: Access to Tetrahydroisoquinolines
  作者：Shuai Fan、Yongzheng Ding、Xiaoxi Chen、Yuzhen Gao、Lei Fu、Shangda Li、Gang Li

  DOI：10.1021/acs.joc.9b01769

  日期：2019.10.18

  A rapid construction of THIQs by a Pd(II)-catalyzed C(sp(2))-H olefination of free primary and secondary 2-phenylethylamines with high step- and atom-economy was reported. Notably, no substituent was required at the alpha-position to the amino group of the 2-phenylethylamines. The substrate scope was broad, and the reaction could also be applied to generate THIQs from the biologically active molecules such as the drug molecule baclofen and phenylalanine ester.
• A conformational restriction approach to the development of dual inhibitors of acetylcholinesterase and serotonin transporter as potential agents for Alzheimer's disease
  作者：Narihiro Toda、Keiko Tago、Shinji Marumoto、Kazuko Takami、Mayuko Ori、Naho Yamada、Kazuo Koyama、Shunji Naruto、Kazumi Abe、Reina Yamazaki、Takao Hara、Atsushi Aoyagi、Yasuyuki Abe、Tsugio Kaneko、Hiroshi Kogen

  DOI：10.1016/s0968-0896(03)00452-8

  日期：2003.10

  Alzheimer's disease (AD) has been treated with acetylcholinesterase (AChE) inhibitors such as donepezil. However, the clinical usefulness of AChE inhibitors is limited mainly due to their adverse peripheral effects. Depression seen in AD patients has been treated with serotonin transporter (SERT) inhibitors. We considered that combining SERT and AChE inhibition could improve the clinical usefulness of AChE inhibitors. In a previous paper, we found a potential dual inhibitor, 1, of AChE (IC50 = 101 nM) and SERT (IC50 = 42 nM), but its AChE inhibition activity was less than donepezil (IC50 = 10 nM). Here, we report the conformationally restricted (R)-18a considerably enhanced inhibitory activity against AChE (IC50 14 nM) and SERT (IC50 = 6 nM). (C) 2003 Elsevier Ltd. All rights reserved.