ethyl 6-amino-7-cyanoindolizine-5-carboxylate | 1679383-13-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并吡啶类
• 英文名称: ethyl 6-amino-7-cyanoindolizine-5-carboxylate
• 英文别名: 5-Indolizinecarboxylic acid, 6-amino-7-cyano-, ethyl ester
• CAS: 1679383-13-1
• 化学式: C₁₂H₁₁N₃O₂
• 分子量: 229.238
• InChiKey: LODUYJZFZPFGOR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  80.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  ethyl 2-(2-formyl-1H-pyrrol-1-yl)acetate 在 哌啶乙酸盐 、 potassium carbonate 作用下， 以 乙醇 为溶剂， 反应 18.0h， 生成 ethyl 6-amino-7-cyanoindolizine-5-carboxylate
  参考文献：
  名称：

  Fluorescent indolizine derivative YI-13 detects amyloid-β monomers, dimers, and plaques in the brain of 5XFAD Alzheimer transgenic mouse model

  摘要：

  阿尔茨海默病（AD）是一种神经退行性疾病，其特征是大脑中淀粉样蛋白-β（Aβ）肽的异常产生和积累。在可溶性寡聚体和不溶性斑块形式中积累的Aβ被认为是该疾病的病理罪魁祸首和生物标志物。在这里，我们报告了一种荧光通用Aβ指示剂YI-13，5-(4-氟苯甲酰)-7,8-二氢吡咯并[1,2-b]异喹啉-9(6H)-酮，它可以检测Aβ单体、二聚体和斑块。我们合成了一个包含吲哚啉核心的26种荧光化学物质库，并通过一系列利用Aβ作为靶点的体外测试对它们进行筛选，YI-13被选为最终的成像候选物。YI-13被发现可以染色和可视化转基因小鼠模型（5XFAD）大脑组织中的不溶性Aβ斑块，通过组织化学方法，并且可以在小鼠模型的大脑裂解物中标记可溶性Aβ寡聚体，通过荧光板阅读器。在从单体聚集的寡聚体和从化学共轭单体合成的二聚体中，YI-13更倾向于二聚体Aβ。

  DOI：

  10.1371/journal.pone.0243041

文献信息

• 인돌리진 유도체, 이의 약학적으로 허용 가능한 염, 이의 제조방법 및 이를 유효성분으로 포함하는 약학적 조성물
  申请人：UIF (University Industry Foundation), Yonsei University 연세대학교 산학협력단(220050095099) BRN ▼110-82-10500

  公开号：KR101558475B1

  公开（公告）日：2015-10-07

  본 발명은 인돌리진 유도체, 이의 약학적으로 허용 가능한 염, 이의 제조방법 및 이를 유효성분으로 포함하는 골 질환 또는 암의 예방 또는 치료용 약학적 조성물에 관한 것이다. 본 발명의 인돌리진 유도체는 파골세포의 분화를 억제하여 골다공증과 같은 파골세포 관련 골 질환에 대한 치료 효과를 나타내며, 암세포의 사멸을 유도하여 항암 활성을 나타내므로, 골 질환과 암에 대한 예방 및 치료제로서 유용하게 이용될 수 있다.

  本发明涉及吲哚啉衍生物，其药学上可接受的盐，其制备方法以及包含其作为有效成分的用于预防或治疗骨疾病或癌症的药学组合物。该吲哚啉衍生物抑制成骨细胞的分化，表现出对与成骨细胞相关的骨疾病如骨质疏松症的治疗效果，并诱导癌细胞凋亡，表现出抗癌活性，因此可作为预防和治疗骨疾病和癌症的药物。
• Synthesis, characterization and biological evaluation of anti-cancer indolizine derivatives via inhibiting β-catenin activity and activating p53
  作者：Seong-Hee Moon、Youngeun Jung、Seong Hwan Kim、Ikyon Kim

  DOI：10.1016/j.bmcl.2015.11.021

  日期：2016.1

  Diversity-oriented construction of new indolizine scaffolds was accomplished by utilizing domino Knoevenagel condensation/intramolecular aldol cyclization. Biological evaluation revealed anticancer activity of these compounds through inhibition of beta-catenin and activation of p53. (C) 2015 Elsevier Ltd. All rights reserved.
• Fluorescent indolizine derivative YI-13 detects amyloid-β monomers, dimers, and plaques in the brain of 5XFAD Alzheimer transgenic mouse model
  作者：DaWon Kim、Jeong Hwa Lee、Hye Yun Kim、Jisu Shin、Kyeonghwan Kim、Sejin Lee、Jinwoo Park、JinIkyon Kim、YoungSoo Kim

  DOI：10.1371/journal.pone.0243041

  日期：——

  Alzheimer disease (AD) is a neurodegenerative disorder characterized by the aberrant production and accumulation of amyloid-β (Aβ) peptides in the brain. Accumulated Aβ in soluble oligomer and insoluble plaque forms are considered to be a pathological culprit and biomarker of the disorder. Here, we report a fluorescent universal Aβ-indicator YI-13, 5-(4-fluorobenzoyl)-7,8-dihydropyrrolo[1,2-b]isoquinolin-9(6H)-one, which detects Aβ monomers, dimers, and plaques. We synthesized a library of 26 fluorescence chemicals with the indolizine core and screen them through a series of in vitro tests utilizing Aβ as a target and YI-13 was selected as the final imaging candidate. YI-13 was found to stain and visualize insoluble Aβ plaques in the brain tissue, of a transgenic mouse model with five familial AD mutations (5XFAD), by a histochemical approach and to label soluble Aβ oligomers within brain lysates of the mouse model under a fluorescence plate reader. Among oligomers aggregated from monomers and synthetic dimers from chemically conjugated monomers, YI-13 preferred the dimeric Aβ.

  阿尔茨海默病（AD）是一种神经退行性疾病，其特征是大脑中淀粉样蛋白-β（Aβ）肽的异常产生和积累。在可溶性寡聚体和不溶性斑块形式中积累的Aβ被认为是该疾病的病理罪魁祸首和生物标志物。在这里，我们报告了一种荧光通用Aβ指示剂YI-13，5-(4-氟苯甲酰)-7,8-二氢吡咯并[1,2-b]异喹啉-9(6H)-酮，它可以检测Aβ单体、二聚体和斑块。我们合成了一个包含吲哚啉核心的26种荧光化学物质库，并通过一系列利用Aβ作为靶点的体外测试对它们进行筛选，YI-13被选为最终的成像候选物。YI-13被发现可以染色和可视化转基因小鼠模型（5XFAD）大脑组织中的不溶性Aβ斑块，通过组织化学方法，并且可以在小鼠模型的大脑裂解物中标记可溶性Aβ寡聚体，通过荧光板阅读器。在从单体聚集的寡聚体和从化学共轭单体合成的二聚体中，YI-13更倾向于二聚体Aβ。