N-(5,6-dimethoxy-3-oxo-indan-1-yl)-2,2,2-trifluoroacetamide | 138621-67-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: N-(5,6-dimethoxy-3-oxo-indan-1-yl)-2,2,2-trifluoroacetamide
• 英文别名: N-(5,6-dimethoxy-3-oxo-2,3-dihydro-1H-inden-1-yl)-2,2,2-trifluoroacetamide；N-(5,6-dimethoxy-3-oxo-1,2-dihydroinden-1-yl)-2,2,2-trifluoroacetamide
• CAS: 138621-67-7
• 化学式: C₁₃H₁₂F₃NO₄
• 分子量: 303.238
• InChiKey: GFZBONQUPPOREX-UHFFFAOYSA-N

物化性质

• 沸点：
  433.3±45.0 °C(Predicted)
• 密度：
  1.40±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  N-(5,6-dimethoxy-3-oxo-indan-1-yl)-2,2,2-trifluoroacetamide 在 chromium(VI) oxide 、 盐酸 、 硫酸 、 水 、 sodium nitrite 作用下， 以 盐酸 、 丙酮 为溶剂， 反应 2.5h， 生成 多奈哌齐2
  参考文献：
  名称：

  Dallemagne, P.; Pilo, J. C.; Rault, S., Bulletin de la Societe Chimique de France, 1993, vol. 130, # 1, p. 121 - 124

  摘要：

  DOI：
• 作为产物：
  描述：

  3,4-二甲氧基苯甲醛 在 ammonium acetate 作用下， 以 乙醇 为溶剂， 反应 2.0h， 生成 N-(5,6-dimethoxy-3-oxo-indan-1-yl)-2,2,2-trifluoroacetamide
  参考文献：
  名称：

  First Synthesis of Racemic Trans Propargylamino-Donepezil, a Pleiotrope Agent Able to Both Inhibit AChE and MAO-B, with Potential Interest against Alzheimer’s Disease

  摘要：

  阿尔茨海默病（AD）是一种多因素神经退行性疾病，使用多靶点定向配体的多效途径现在被认为可能很方便。在今天已经验证的许多针对AD的靶点中，乙酰胆碱酯酶（ACh）和单胺氧化酶-B（MAO-B）似乎尤其令人信服，特别是如果由单一药物如拉多斯蒂吉尔来显示，目前正在AD的临床试验中。考虑到这些结果，我们想利用多奈哌齐（DPZ）和拉沙吉林这两个因丹烯衍生物的结构类似性，并提出这两种化合物之间的结构妥协的合成和初步的体外生物学特性，我们称之为丙炔基氨基多奈哌齐（PADPZ）。合成了外消旋的trans PADPZ，并通过其生物评价确定了其对（h）AChE（IC50 = 0.4 µM）和（h）MAO-B（IC50 = 6.4 µM）的抑制活性。

  DOI：

  10.3390/molecules26010080

文献信息

• Design, synthesis and biological evaluation of novel indano- and thiaindano-pyrazoles with potential interest for Alzheimer's disease
  作者：David Genest、Christophe Rochais、Cédric Lecoutey、Jana Sopkova-de Oliveira Santos、Céline Ballandonne、Sabrina Butt-Gueulle、Remi Legay、Marc Since、Patrick Dallemagne

  DOI：10.1039/c3md00041a

  日期：——

  The synthesis of eighteen novel (thia)indanopyrazole derivatives was achieved starting from amino(thia)indanones. Some of them displayed a dual binding site acetylcholinesterase inhibition which makes them potentially interesting for Alzheimer's disease treatment.

  从氨基(噻)茚酮开始，合成了 18 种新型(噻)茚并吡唑衍生物。其中一些衍生物显示出双结合位点乙酰胆碱酯酶抑制作用，这使它们具有治疗阿尔茨海默病的潜在意义。
• One-pot cyclization of alkoxy-3-aminoindan-1-ones.
  作者：Patrick Dallemagne、Sylvain Rault、Juan Carlos Pilo、Marie Paule Foloppe、Max Robba

  DOI：10.1016/0040-4039(91)80160-8

  日期：1991.10

  3-Amino-3-alkoxyphenylpropionic acids, prepared from alkoxybenzaldehydes, are cyclized in one step into 3-aminoindan-1-ones using trifluoroacetic acid and trifluoroacetic anhydride.
• Evidence for new non-steroidal human aromatase inhibitors and comparison with equine aromatase inhibition for an understanding of the mammalian active site
  作者：Pierrick Auvray、Safa Moslemi、Pascal Sourdaine、Sébastien Galopin、Gilles-Eric Séralini、Cécile Enguehard、Patrick Dallemagne、Ronan Bureau、Pascal Sonnet、Sylvain Rault

  DOI：10.1016/s0223-5234(98)80046-9

  日期：1998.6

  We developed a new comparative model in order to better understand the structure-function relationships of the active site in human aromatase. Thus, we undertook the comparative inhibition of human and equine aromatases with new compounds. In fact, equine aromatase represents the only easy and available mammalian membrane-bound enzyme model, besides the human one, which is biochemically purified, well characterized and cloned. During the course of our work concerning the synthesis and screening of new drugs on human and equine aromatases, we identified two new indane derivatives which inhibited the human enzyme (IC50 = 3.5 mu M and 5.9 mu M) strongly and selectively while they were much less active on the equine one (IC50 > 10 mu M). The hitherto known aromatase inhibitors, such as 4-hydroxyandrostenedione (4-OHA) and some other indane-related derivatives, are equally efficient on both human and equine enzymes. In this work, using a theoretical 3D model of aromatase, we have explained the human selectivity of the new described compounds as due to the specific differences between the primary structure of both active sites in human and equine enzymes. These results could allow synthesis of a new family of compounds that are much more potent and selective aromatase inhibitors. (C) Elsevier, Paris.
• First Synthesis of Racemic Trans Propargylamino-Donepezil, a Pleiotrope Agent Able to Both Inhibit AChE and MAO-B, with Potential Interest against Alzheimer’s Disease
  作者：Benjamin Guieu、Cedric Lecoutey、Rémi Legay、Audrey Davis、Jana Sopkova de Oliveira Santos、Cosimo Damiano Altomare、Marco Catto、Christophe Rochais、Patrick Dallemagne

  DOI：10.3390/molecules26010080

  日期：——

  Alzheimer’s disease (AD) is a multifactorial neurodegenerative disease towards which pleiotropic approach using Multi-Target Directed Ligands is nowadays recognized as probably convenient. Among the numerous targets which are today validated against AD, acetylcholinesterase (ACh) and Monoamine Oxidase-B (MAO-B) appear as particularly convincing, especially if displayed by a sole agent such as ladostigil, currently in clinical trial in AD. Considering these results, we wanted to take benefit of the structural analogy lying in donepezil (DPZ) and rasagiline, two indane derivatives marketed as AChE and MAO-B inhibitors, respectively, and to propose the synthesis and the preliminary in vitro biological characterization of a structural compromise between these two compounds, we called propargylaminodonepezil (PADPZ). The synthesis of racemic trans PADPZ was achieved and its biological evaluation established its inhibitory activities towards both (h)AChE (IC50 = 0.4 µM) and (h)MAO-B (IC50 = 6.4 µM).

  阿尔茨海默病（AD）是一种多因素神经退行性疾病，使用多靶点定向配体的多效途径现在被认为可能很方便。在今天已经验证的许多针对AD的靶点中，乙酰胆碱酯酶（ACh）和单胺氧化酶-B（MAO-B）似乎尤其令人信服，特别是如果由单一药物如拉多斯蒂吉尔来显示，目前正在AD的临床试验中。考虑到这些结果，我们想利用多奈哌齐（DPZ）和拉沙吉林这两个因丹烯衍生物的结构类似性，并提出这两种化合物之间的结构妥协的合成和初步的体外生物学特性，我们称之为丙炔基氨基多奈哌齐（PADPZ）。合成了外消旋的trans PADPZ，并通过其生物评价确定了其对（h）AChE（IC50 = 0.4 µM）和（h）MAO-B（IC50 = 6.4 µM）的抑制活性。
• Dallemagne, P.; Pilo, J. C.; Rault, S., Bulletin de la Societe Chimique de France, 1993, vol. 130, # 1, p. 121 - 124
  作者：Dallemagne, P.、Pilo, J. C.、Rault, S.、Robba, M.

  DOI：——

  日期：——