isobutyl N-(coumarin-3-yl)carbamate | 1442690-85-8

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 英文名称: isobutyl N-(coumarin-3-yl)carbamate
• 英文别名: isobutyl (coumarin-3-yl)carbamate；2-methylpropyl N-(2-oxochromen-3-yl)carbamate
• CAS: 1442690-85-8
• 化学式: C₁₄H₁₅NO₄
• 分子量: 261.277
• InChiKey: WJDOZVLLYHCHJG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  3-氨基香豆素 、 氯甲酸异丁酯 在 吡啶 作用下， 以 二氯甲烷 为溶剂， 以78%的产率得到isobutyl N-(coumarin-3-yl)carbamate
  参考文献：
  名称：

  Targeting adenosine receptors with coumarins: synthesis and binding activities of amide and carbamate derivatives

  摘要：

  摘要 目的 为了找出影响对腺苷受体（ARs）结合活性和选择性的结构特征，合成了几种具有酰胺（化合物3-6）和碳酸酯（7-9）功能的3-取代香豆素。为了研究对结合活性和选择性的可能影响，在香豆素基团的4位还引入了一个羟基取代基。 方法 合成了一系列新的香豆素（3-9），并通过放射配体结合研究对ARs进行评估。 主要发现 4-羟基衍生物（4、8和9）中没有一个显示出对任何ARs的结合亲和力。没有任何化合物与hA2B AR相互作用（Ki > 100,000 nm）。化合物3、5、6和7具有不同的活性特征，对人类A1、A2A和A3 ARs的结合亲和力和选择性不同。 结论 最显著的衍生物是化合物7，它对A3腺苷受体具有最佳的亲和力和选择性（Ki = 5500 nm）。

  DOI：

  10.1111/j.2042-7158.2012.01571.x

文献信息

• Targeting adenosine receptors with coumarins: synthesis and binding activities of amide and carbamate derivatives
  作者：Maria João Matos、Alexandra Gaspar、Sonja Kachler、Karl-Norbert Klotz、Fernanda Borges、Lourdes Santana、Eugenio Uriarte

  DOI：10.1111/j.2042-7158.2012.01571.x

  日期：2012.12.5

  With the aim of finding the structural features governing binding activity and selectivity against adenosine receptors (ARs), several 3-subtituted coumarins with amide (compounds 3–6) and carbamate (7–9) functions were synthesized. To study its possible influence on the binding activity and selectivity, a hydroxyl substituent was also introduced at position 4 of the coumarin moiety.

  A new series of coumarins (3–9) were synthesized and evaluated by radioligand binding studies towards ARs.

  None of the 4-hydroxy derivatives (4, 8 and 9) showed binding affinity for any of the ARs. None of the compounds interacted with the hA2B AR (Ki > 100 000 nm). Compounds 3, 5, 6 and 7 had different activity profiles with dissimilar binding affinity and selectivity towards human A1, A2A and A3 ARs.

  The most remarkable derivative is compound 7, which presents the best affinity and selectivity for the A3 adenosine receptor (Ki = 5500 nm).

  摘要 目的 为了找出影响对腺苷受体（ARs）结合活性和选择性的结构特征，合成了几种具有酰胺（化合物3-6）和碳酸酯（7-9）功能的3-取代香豆素。为了研究对结合活性和选择性的可能影响，在香豆素基团的4位还引入了一个羟基取代基。 方法 合成了一系列新的香豆素（3-9），并通过放射配体结合研究对ARs进行评估。 主要发现 4-羟基衍生物（4、8和9）中没有一个显示出对任何ARs的结合亲和力。没有任何化合物与hA2B AR相互作用（Ki > 100,000 nm）。化合物3、5、6和7具有不同的活性特征，对人类A1、A2A和A3 ARs的结合亲和力和选择性不同。 结论 最显著的衍生物是化合物7，它对A3腺苷受体具有最佳的亲和力和选择性（Ki = 5500 nm）。
• Novel (coumarin-3-yl)carbamates as selective MAO-B inhibitors: Synthesis, in vitro and in vivo assays, theoretical evaluation of ADME properties and docking study
  作者：Maria J. Matos、Santiago Vilar、Rosa Mª Gonzalez-Franco、Eugenio Uriarte、Lourdes Santana、Carol Friedman、Nicholas P. Tatonetti、Dolores Viña、Jose A. Fontenla

  DOI：10.1016/j.ejmech.2013.02.009

  日期：2013.5

  A series of (coumarin-3-yl)carbamates was synthesized and evaluated in vitro as monoamine oxidase (MAO-A and MAO-B) inhibitors. Most of the new compounds selectively inhibited MAO-B isoenzyme with IC50 values in the micro or nanoMolar ranges. Since these compounds must achieve the brain cells, theoretical evaluation of ADME properties were also carried out. Compound 8 (benzyl(coumarin-3yl)carbamate), which presented the most interesting in vitro MAO-B inhibitory profile (IC50 against MAO-B = 45 nM), was subjected to further studies. This in vitro MAO-B inhibitory activity is comparable with that of the selegiline, the reference compound (IC50 against MAO-B = 20 nM). Taking into account the in vitro results of compound 8, in vivo assays and docking calculations were also carried out for this derivative. (C) 2013 Elsevier Masson SAS. All rights reserved.