ethyl 1-cyclopropyl-4-oxopiperidine-3-carboxylate | 49681-84-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: ethyl 1-cyclopropyl-4-oxopiperidine-3-carboxylate
• 英文别名: 1-cyclopropyl-3-carbethoxy-4-piperidone
• CAS: 49681-84-7
• 化学式: C₁₁H₁₇NO₃
• 分子量: 211.261
• InChiKey: CYTHCMOPAYRQRJ-UHFFFAOYSA-N

物化性质

• 沸点：
  315.8±37.0 °C(Predicted)
• 密度：
  1?+-.0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl 1-cyclopropyl-4-oxopiperidine-3-carboxylate 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 sodium methylate 、 potassium carbonate 、 N,N-二异丙基乙胺 、 三氯氧磷 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 60.0h， 生成 2-(3-(6-cyclopropyl-4-((4-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-4-yl)phenyl)amino)-5,6,7,8-tetrahydro-pyrido[4,3-d]pyrimidin-2-yl)phenoxy)-N-isopropylacetamide
  参考文献：
  名称：

  Discovery and Optimization of Glucose Uptake Inhibitors

  摘要：

  Aerobic glycolysis, originally identified by Warburg as a hallmark of cancer, has recently been implicated in immune cell activation and growth. Glucose, the starting material for glycolysis, is transported through the cellular membrane by a family of glucose transporters (GLUTs). Therefore, targeting glucose transporters to regulate aerobic glycolysis is an attractive approach to identify potential therapeutic agents for cancers and autoimmune diseases. Herein, we describe the discovery and optimization of a class of potent, orally bioavailable inhibitors of glucose transporters, targeting both GLUT1 and GLUT3.

  DOI：

  10.1021/acs.jmedchem.9b02153
• 作为产物：
  描述：

  Diethyl-3,3'-(cyclopropylimino)-dipropionat 在 乙醇 、 sodium hydride 、 溶剂黄146 作用下， 以 四氢呋喃 为溶剂， 反应 24.0h， 生成 ethyl 1-cyclopropyl-4-oxopiperidine-3-carboxylate
  参考文献：
  名称：

  [EN] NAPHTHALINE DERIVATIVES USEFUL AS HISTAMINE-3-RECEPTOR LIGANDS
  [FR] DERIVES DE LA NAPHTALINE UTILISES COMME LIGANDS DU RECEPTEUR 3 DE L'HISTAMINE

  摘要：

  本发明涉及式（I）的化合物，其中A，R1和R2如描述和索赔中所定义，以及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。这些化合物可用于治疗和/或预防与H3受体调节相关的疾病。

  公开号：

  WO2005117865A1

文献信息

• [EN] NAPHTHALINE DERIVATIVES USEFUL AS HISTAMINE-3-RECEPTOR LIGANDS<br/>[FR] DERIVES DE LA NAPHTALINE UTILISES COMME LIGANDS DU RECEPTEUR 3 DE L'HISTAMINE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2005117865A1

  公开（公告）日：2005-12-15

  The present invention relates to compounds of formula (I) wherein A, R1 and R2 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A，R1和R2如描述和索赔中所定义，以及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。这些化合物可用于治疗和/或预防与H3受体调节相关的疾病。
• 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.
• US3991199A
  申请人：——

  公开号：US3991199A

  公开（公告）日：1976-11-09
• US4005208A
  申请人：——

  公开号：US4005208A

  公开（公告）日：1977-01-25
• US4174453A
  申请人：——

  公开号：US4174453A

  公开（公告）日：1979-11-13