5-(1-tert-butoxycarbonyl-piperidin-4-yloxy)-1H-indole-2-carboxylic acid ethyl ester | 937718-73-5

• 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-(1-tert-butoxycarbonyl-piperidin-4-yloxy)-1H-indole-2-carboxylic acid ethyl ester
• 英文别名: ethyl 5-[1-[(2-methylpropan-2-yl)oxycarbonyl]piperidin-4-yl]oxy-1H-indole-2-carboxylate
• CAS: 937718-73-5
• 化学式: C₂₁H₂₈N₂O₅
• 分子量: 388.464
• InChiKey: BMZTWESVFYOVES-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  28
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  80.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-(1-tert-butoxycarbonyl-piperidin-4-yloxy)-1H-indole-2-carboxylic acid ethyl ester 在 lithium hydroxide monohydrate 、 水 、 盐酸 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 16.0h， 以96%的产率得到5-(1-tert-butoxycarbonyl-piperidin-4-yloxy)-1H-indole-2-carboxylic acid hydrochloride/lithium chloride complex
  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：

  4-[3-(2-ethoxycarbonyl-2-oxo-ethyl)-4-nitro-phenoxy]-piperidine-1-carboxylic acid tert-butyl ester 在 钯 乙醇 、 乙酸乙酯 、 正庚烷 作用下， 以 乙醇 为溶剂， 反应 9.0h， 以to yield 25.998 g (69%) as white crystals的产率得到5-(1-tert-butoxycarbonyl-piperidin-4-yloxy)-1H-indole-2-carboxylic acid ethyl ester
  参考文献：
  名称：

  1,5-Substituted indol-2-yl amide derivatives

  摘要：

  本发明涉及式I的化合物，其中R1至R4和G如说明书和权利要求所定义，并且其药学上可接受的盐。该化合物可用于治疗和/或预防与H3受体调节相关的疾病。

  公开号：

  US20070123515A1

文献信息

• 1,5-Substituted indol-2-yl amide derivatives
  申请人：Nettekoven Matthias

  公开号：US20070123515A1

  公开（公告）日：2007-05-31

  The present invention relates to compounds of formula I wherein R 1 to R 4 and G are as defined in the description and claims and pharmaceutically acceptable salts thereof. 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R1至R4和G如描述和索赔中定义的，并且其药学上可接受的盐。这些化合物可用于治疗和/或预防与H3受体调节相关的疾病。
• 1,5-SUBSTITUTED INDOL-2-YL AMIDE DERIVATIVES
  申请人：F.HOFFMANN-LA ROCHE AG

  公开号：EP1957479A2

  公开（公告）日：2008-08-20
• US7745479B2
  申请人：——

  公开号：US7745479B2

  公开（公告）日：2010-06-29
• [EN] 1,5-SUBSTITUTED INDOL-2-YL AMIDE DERIVATIVES<br/>[FR] DERIVES DE INDOLE-2-YL AMIDE SUBSTITUES EN 1,5
  申请人：HOFFMANN LA ROCHE

  公开号：WO2007062999A2

  公开（公告）日：2007-06-07

  [EN] The present invention relates to compounds of formula I wherein R¹ to R⁴ and G are as defined in the description and claims and pharmaceutically acceptable salts thereof. The compounds are useful for the treatment and/or prevention of diseases which are associated with the modulation of H3 receptors.
  [FR] L'invention concerne des composés représentés par la formule (I), dans laquelle R¹ à R⁴ et G sont tels que définis dans la description et les revendications, ainsi que les sels de qualité pharmaceutique associés. Ces composés sont utilisés dans le traitement et/ou la prévention de maladies associées à la modulation des récepteurs H3.
• 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.