1-carbethoxymethylene-6-methoxy-1,2,3,4-tetrahydroisoquinoline | 96077-49-5

• 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-carbethoxymethylene-6-methoxy-1,2,3,4-tetrahydroisoquinoline
• 英文别名: ethyl (2E,Z)-(6-methoxy-3,4-dihydro-1(2H)-isoquinolinylidene)-ethanoate；ethyl (6-methoxy-3,4-dihydro-2H-isoquinolin-1-yliden)-acetate；6-Methoxy-1-ethoxycarbonylmethylen-1,2,3,4-tetrahydro-isochinolin；Ethyl (6-methoxy-3,4-dihydro-2H-isoquinolin-1-yliden)-acetate；ethyl 2-(6-methoxy-3,4-dihydro-2H-isoquinolin-1-ylidene)acetate
• CAS: 96077-49-5
• 化学式: C₁₄H₁₇NO₃
• 分子量: 247.294
• InChiKey: KWAAFNXNDFSXFA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  47.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-carbethoxymethylene-6-methoxy-1,2,3,4-tetrahydroisoquinoline 在 platinum(IV) oxide 盐酸 、 lithium aluminium tetrahydride 、 氢气 、 三溴化硼 、 potassium carbonate 、 溶剂黄146 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 23.17h， 生成 dimethylcarbamic acid 1-[2-(4-nitrophenoxy)ethyl]-1,2,3,4-tetrahydroisoquinolin-6-yl 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：

  N-(3-Methoxy-phenethyl)-malonsaeure-ethylester-amid 在 三氯氧磷 作用下， 反应 4.0h， 以7.56 g的产率得到1-carbethoxymethylene-6-methoxy-1,2,3,4-tetrahydroisoquinoline
  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

• Pyrrolo[2.1-a]isoquinoline derivatives
  申请人：——

  公开号：US20030236276A1

  公开（公告）日：2003-12-25

  The present invention relates to pyrrolo[2.1-a]isoquinolines which are inhibitors of phosphodiesterase 10a, a process for preparing these compounds and a method of treating cancer in humans and animals by administering these compounds.

  本发明涉及一种对磷酸二酯酶10a具有抑制作用的吡咯并[2.1-a]异喹啉类化合物，以及制备这些化合物的方法和通过给人类和动物投药这些化合物来治疗癌症的方法。
• Benzylamine analogues
  申请人：SANKYO COMPANY, LIMITED

  公开号：US20040067981A1

  公开（公告）日：2004-04-08

  A compound of the formula (I): 1 wherein R 1 represents C 1 -C 6 alkyl, amino (C 1 -C 6 alkyl)amino, di(C 1 -C 6 alkyl) amino or a nitrogen-containing saturated heterocyclic; R 2 and R 3 are the same or different and represent hydrogen or C 1 -C 6 alkyl; R a represents C 1 -C 6 alkyl or C 2 -C 6 alkenyl or together with R 2 represents a C 1 -C 3 alkylene; Arom represents aryl or heteroaryl; A represents a C 1 -C 6 alkylene; E represents a single bond, oxygen, sulfur or R 4 NR 4 —, wherein R 4 is hydrogen or C 1 -C 7 alkenoyl; X 1 and X 2 are the same or different and represent oxygen or sulfur; or a pharmacologically acceptable salt or ester thereof. The compound has superior acetylcholinesterase inhibitory action and selective serotonin reuptake inhibitory action, and is useful for treating or preventing Alzheimer's disease, depression, Huntington's chorea, Pick's disease, tardive dyskinesia, compulsive disorders or panic disorders.

  化合物的化学式为（I）：1，其中R1代表C1-C6烷基，氨基（C1-C6烷基）氨基，二（C1-C6烷基）氨基或含氮饱和杂环；R2和R3相同或不同，代表氢或C1-C6烷基；R代表C1-C6烷基或C2-C6烯基或与R2一起代表C1-C3烷基；Arom代表芳基或杂芳基；A代表C1-C6烷基；E代表单键，氧，硫或R4NR4—，其中R4为氢或C1-C7烯酰基；X1和X2相同或不同，代表氧或硫；或其药学上可接受的盐或酯。该化合物具有优异的乙酰胆碱酯酶抑制作用和选择性5-羟色胺再摄取抑制作用，并可用于治疗或预防阿尔茨海默病、抑郁症、亨廷顿舞蹈症、皮克病、迟发性运动障碍、强迫性障碍或惊恐障碍。
• BENZYLAMINE ANALOGUE
  申请人：BTG INTERNATIONAL LIMITED

  公开号：EP1362844B1

  公开（公告）日：2007-12-05
• 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.