1-acetyl-5-fluoro-1H-indole-3-carboxylic acid | 1260799-33-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 1-acetyl-5-fluoro-1H-indole-3-carboxylic acid
• 英文别名: 1-acetyl-5-fluoroindole-3-carboxylic acid
• CAS: 1260799-33-4
• 化学式: C₁₁H₈FNO₃
• 分子量: 221.188
• InChiKey: TWAJMWNSMYUOSM-UHFFFAOYSA-N

物化性质

• 沸点：
  403.5±25.0 °C(Predicted)
• 密度：
  1.40±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  59.3
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-acetyl-5-fluoro-1H-indole-3-carboxylic acid 在 4-二甲氨基吡啶 、 potassium carbonate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 {3-[4-(4-butyryl-5-methyl-pyrazol-1-yl)phenylcarbamoyl]-5-fluoro-indol-1-yl}acetic acid methyl ester
  参考文献：
  名称：

  N-[6-(4-Butanoyl-5-methyl-1H-pyrazol-1-yl)pyridazin-3-yl]-5-chloro-1-[2-(4-methylpiperazin-1-yl)-2-oxoethyl]-1H-indole-3-carboxamide (SAR216471), a Novel Intravenous and Oral, Reversible, and Directly Acting P2Y12 Antagonist

  摘要：

  In the search of a potential backup for clopidogrel, we have initiated a HTS campaign designed to identify novel reversible P2Y12 antagonists. Starting from a hit with low micromolar binding activity, we report here the main steps of the optimization process leading to the identification of the preclinical candidate SAR216471. It is a potent, highly selective, and reversible P2Y12 receptor antagonist and by far the most potent inhibitor of ADP-induced platelet aggregation among the P2Y12 antagonists described in the literature. SAR216471 displays potent in vivo antiplatelet and antithrombotic activities and has the potential to differentiate from other antiplatelet agents.

  DOI：

  10.1021/jm500588w
• 作为产物：
  描述：

  2,2,2-三氟-1-(5-氟-1H-吲哚-3-基)乙烷-1-酮 在 4-二甲氨基吡啶 、 水 、 三乙胺 、 potassium hydroxide 作用下， 以 二氯甲烷 为溶剂， 生成 1-acetyl-5-fluoro-1H-indole-3-carboxylic acid
  参考文献：
  名称：

  N-[6-(4-Butanoyl-5-methyl-1H-pyrazol-1-yl)pyridazin-3-yl]-5-chloro-1-[2-(4-methylpiperazin-1-yl)-2-oxoethyl]-1H-indole-3-carboxamide (SAR216471), a Novel Intravenous and Oral, Reversible, and Directly Acting P2Y12 Antagonist

  摘要：

  In the search of a potential backup for clopidogrel, we have initiated a HTS campaign designed to identify novel reversible P2Y12 antagonists. Starting from a hit with low micromolar binding activity, we report here the main steps of the optimization process leading to the identification of the preclinical candidate SAR216471. It is a potent, highly selective, and reversible P2Y12 receptor antagonist and by far the most potent inhibitor of ADP-induced platelet aggregation among the P2Y12 antagonists described in the literature. SAR216471 displays potent in vivo antiplatelet and antithrombotic activities and has the potential to differentiate from other antiplatelet agents.

  DOI：

  10.1021/jm500588w

文献信息

• Decarboxylative halogenation of indoles by vanadium haloperoxidases
  作者：Lauren J. Harstad、Clare E. Wells、Hyung Ji Lee、Lauren P. T. Ramos、Manik Sharma、Cameron A. Pascoe、Kyle F. Biegasiewicz

  DOI：10.1039/d3cc04053d

  日期：——

  Halogenated heteroarenes are key building blocks across numerous chemical industries. Here, we report that vanadium haloperoxidases are capable of producing 3-haloindoles through decarboxylative halogenation of 3-carboxyindoles. This biocatalytic method is applicable to decarboxylative chlorination, bromination, and iodination in moderate to high yields and with excellent chemoselectivity.

  卤化杂芳烃是众多化学工业的关键组成部分。在这里，我们报道钒卤过氧化物酶能够通过 3-羧基吲哚的脱羧卤化产生 3-卤代吲哚。该生物催化方法适用于中等到高产率的脱羧氯化、溴化和碘化，并且具有优异的化学选择性。
• <i>N</i>-[6-(4-Butanoyl-5-methyl-1<i>H</i>-pyrazol-1-yl)pyridazin-3-yl]-5-chloro-1-[2-(4-methylpiperazin-1-yl)-2-oxoethyl]-1<i>H</i>-indole-3-carboxamide (SAR216471), a Novel Intravenous and Oral, Reversible, and Directly Acting P2Y12 Antagonist
  作者：Christophe Boldron、Angélina Besse、Marie-Françoise Bordes、Stéphanie Tissandié、Xavier Yvon、Benjamin Gau、Alain Badorc、Tristan Rousseaux、Guillaume Barré、Jérôme Meneyrol、Gernot Zech、Marc Nazare、Valérie Fossey、Anne-Marie Pflieger、Sandrine Bonnet-Lignon、Laurence Millet、Christophe Briot、Frédérique Dol、Jean-Pascal Hérault、Pierre Savi、Gilbert Lassalle、Nathalie Delesque、Jean-Marc Herbert、Françoise Bono

  DOI：10.1021/jm500588w

  日期：2014.9.11

  In the search of a potential backup for clopidogrel, we have initiated a HTS campaign designed to identify novel reversible P2Y12 antagonists. Starting from a hit with low micromolar binding activity, we report here the main steps of the optimization process leading to the identification of the preclinical candidate SAR216471. It is a potent, highly selective, and reversible P2Y12 receptor antagonist and by far the most potent inhibitor of ADP-induced platelet aggregation among the P2Y12 antagonists described in the literature. SAR216471 displays potent in vivo antiplatelet and antithrombotic activities and has the potential to differentiate from other antiplatelet agents.