5-fluoro-6-hydroxy-1H-indole-2-carboxylic acid methyl ester | 872030-47-2

• 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: 5-fluoro-6-hydroxy-1H-indole-2-carboxylic acid methyl ester
• 英文别名: Methyl 5-fluoro-6-hydroxy-1H-indole-2-carboxylate
• CAS: 872030-47-2
• 化学式: C₁₀H₈FNO₃
• 分子量: 209.177
• InChiKey: AQNPHJZHDHFRKM-UHFFFAOYSA-N

物化性质

• 沸点：
  389.2±37.0 °C(Predicted)
• 密度：
  1.468±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  62.3
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-异丙基-4-哌啶醇 、 5-fluoro-6-hydroxy-1H-indole-2-carboxylic acid methyl ester 在 三丁基膦 、 1,1'-azodicarbonyl-dipiperidine 作用下， 以 四氢呋喃 为溶剂， 以48%的产率得到5-fluoro-6-(1-isopropyl-piperidin-4-yloxy)-1H-indole-2-carboxylic acid methyl ester
  参考文献：
  名称：

  5-Hydroxyindole-2-carboxylic Acid Amides: Novel Histamine-3 Receptor Inverse Agonists for the Treatment of Obesity

  摘要：

  Obesity is a major risk factor in the development of conditions such as hypertension, hyperglycemia, dyslipidemia, coronary artery disease, and cancer. Several pieces of evidence across different species, including primates, underscore the implication of the histamine 3 receptor (H3R) in the regulation of food intake and body weight and the potential therapeutic effect Of H3R inverse agonists. A pharmacophore model, based on public information and validated by previous investigations, was used to design several potential scaffolds. Out of these scaffolds. the 5-hydroxyindole-2-carboxylic acid amide appeared to be of great potential as a novel series of H-3 inverse agonist. Extensive structure-activity relationships revealed the interconnectivity of microsomal clearance and hERG (human ether-a-go-go-related gene) affinity with lipophilicity, artificial membrane permeation, and basicity. This effort led to the identification of compounds reversing the (R)-alpha-methylhistamine-induced water intake increase in Wistar rats and, further, reducing food intake in diet-induced obese Sprague-Dawley rats. Of these, the biochemical, pharmacokinetic, and pharmacodynamic characteristics of (4,4-difluoropiperidin-1-yl)[1-isopropyl-5-(1-isopropylpiperidin-4-yloxy)1H-indol-2-yl]-methanone 36 are detailed.

  DOI：

  10.1021/jm900409x
• 作为产物：
  描述：

  6-benzyloxy-5-fluoro-1H-indole-2-carboxylic acid methyl ester 在 钯 乙酸乙酯 、 乙醚 作用下， 以 乙酸乙酯 为溶剂， 40.0 ℃ 、13.33 MPa 条件下， 反应 2.0h， 以to yield 10.9 g (74%) of the title compound as white crystals的产率得到5-fluoro-6-hydroxy-1H-indole-2-carboxylic acid methyl ester
  参考文献：
  名称：

  Indole derivatives as H3 inverse agonists

  摘要：

  本发明涉及式I的化合物：其中X，R1，R2，R3，R4和R5如描述和权利要求中所定义的那样，以及其药学上可接受的盐，以制备这些化合物和含有它们的制药组合物。这些化合物对于治疗和/或预防与H3受体调节相关的疾病是有用的。

  公开号：

  US07361682B2

文献信息

• [EN] INDOLE DERIVATIVES AS HISTAMINE RECEPTOR ANTAGONISTS<br/>[FR] DERIVES D'INDOLE UTILISES COMME ANTAGONISTES DU RECEPTEUR DE L'HISTAMINE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2005123716A1

  公开（公告）日：2005-12-29

  The present invention relates to compounds of formula (I) wherein X, R1, R2, R3, R4 and R5 are as defined in the description and claims, and pharmaceutically acceptable salts thereof, to the preparation of such compounds and pharmaceutical compositions containing them. The compounds are useful for the treatment and/or prevention of diseases which are associated with the modulation of H3 receptors.

  本发明涉及式（I）的化合物，其中X、R1、R2、R3、R4和R5如描述和权利要求中所定义，并其药学上可接受的盐，以及制备这些化合物和含有它们的药物组合物。这些化合物对于治疗和/或预防与H3受体调节相关的疾病是有用的。
• Indole derivatives as H3 inverse agonists
  申请人：McArthur Gatti Silvia

  公开号：US20050282864A1

  公开（公告）日：2005-12-22

  The present invention relates to compounds of formula I: wherein X, R 1 , R 2 , R 3 , R 4 and R 5 are as defined in the description and claims, and pharmaceutically acceptable salts thereof, to the preparation of such compounds and pharmaceutical compositions containing them. The compounds are useful for the treatment and/or prevention of diseases which are associated with the modulation of H3 receptors.

  本发明涉及式I的化合物：其中X，R1，R2，R3，R4和R5如描述和权利要求中所定义，并且其药学上可接受的盐，以及制备这些化合物和含有它们的制药组合物。这些化合物对于与H3受体调节相关的疾病的治疗和/或预防是有用的。
• INDOLE DERIVATIVES AS HISTAMINE RECEPTOR ANTAGONISTS
  申请人：F.HOFFMANN-LA ROCHE AG

  公开号：EP1761519A1

  公开（公告）日：2007-03-14
• US7361682B2
  申请人：——

  公开号：US7361682B2

  公开（公告）日：2008-04-22
• 5-Hydroxyindole-2-carboxylic Acid Amides: Novel Histamine-3 Receptor Inverse Agonists for the Treatment of Obesity
  作者：Pascale David Pierson、Alec Fettes、Christian Freichel、Silvia Gatti-McArthur、Cornelia Hertel、Jörg Huwyler、Peter Mohr、Toshito Nakagawa、Matthias Nettekoven、Jean-Marc Plancher、Susanne Raab、Hans Richter、Olivier Roche、Rosa María Rodríguez Sarmiento、Monique Schmitt、Franz Schuler、Tadakatsu Takahashi、Sven Taylor、Christoph Ullmer、Ruby Wiegand

  DOI：10.1021/jm900409x

  日期：2009.7.9

  Obesity is a major risk factor in the development of conditions such as hypertension, hyperglycemia, dyslipidemia, coronary artery disease, and cancer. Several pieces of evidence across different species, including primates, underscore the implication of the histamine 3 receptor (H3R) in the regulation of food intake and body weight and the potential therapeutic effect Of H3R inverse agonists. A pharmacophore model, based on public information and validated by previous investigations, was used to design several potential scaffolds. Out of these scaffolds. the 5-hydroxyindole-2-carboxylic acid amide appeared to be of great potential as a novel series of H-3 inverse agonist. Extensive structure-activity relationships revealed the interconnectivity of microsomal clearance and hERG (human ether-a-go-go-related gene) affinity with lipophilicity, artificial membrane permeation, and basicity. This effort led to the identification of compounds reversing the (R)-alpha-methylhistamine-induced water intake increase in Wistar rats and, further, reducing food intake in diet-induced obese Sprague-Dawley rats. Of these, the biochemical, pharmacokinetic, and pharmacodynamic characteristics of (4,4-difluoropiperidin-1-yl)[1-isopropyl-5-(1-isopropylpiperidin-4-yloxy)1H-indol-2-yl]-methanone 36 are detailed.