ethyl 3-oxo-3-[(2R)-tetrahydrofuran-2-yl]propanoate | 1161825-32-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 酮酸及其衍生物
• 英文名称: ethyl 3-oxo-3-[(2R)-tetrahydrofuran-2-yl]propanoate
• 英文别名: ethyl 3-oxo-3-((2R)-tetrahydrofuran-2-yl)propionate；Ethyl (2R)-tetrahydro-I(2)-oxo-2-furanpropanoate；ethyl 3-oxo-3-[(2R)-oxolan-2-yl]propanoate
• CAS: 1161825-32-6
• 化学式: C₉H₁₄O₄
• 分子量: 186.208
• InChiKey: DVSIOGDCWXTPTK-MRVPVSSYSA-N

物化性质

• 沸点：
  268.8±30.0 °C(Predicted)
• 密度：
  1.135±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  13
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl 3-oxo-3-[(2R)-tetrahydrofuran-2-yl]propanoate 在 氯化亚砜 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 3.5h， 生成 ethyl 2-ethyl-4-[(2R)-tetrahydrofuran-2-yl]thiazole-5-carboxylate
  参考文献：
  名称：

  Optimization of Brain Penetrant 11β-Hydroxysteroid Dehydrogenase Type I Inhibitors and in Vivo Testing in Diet-Induced Obese Mice

  摘要：

  11 beta-Hydroxysteroid dehydrogenase type 1 (11 beta-HSD1) has been widely considered by the pharmaceutical industry as a target to treat metabolic syndrome in type II diabetics. We hypothesized that central nervous system (CNS) penetration might be required to see efficacy. Starting from a previously reported pyrimidine compound, we removed hydrogen-bond donors to yield 3, which had modest CNS penetration. More significant progress was achieved by changing the core to give 40, which combines good potency and CNS penetration. Compound 40 was dosed to diet-induced obese (DIO) mice and gave excellent target engagement in the liver and high free exposures of drug, both peripherally and in the CNS. However, no body weight reduction or effects on glucose or insulin were observed in this model. Similar data were obtained with a structurally diverse thiazole compound 51. This work casts doubt on the hypothesis that localized tissue modulation of 11 beta-HSD1 activity alleviates metabolic syndrome.

  DOI：

  10.1021/jm4016729
• 作为产物：
  描述：

  丙二酸单乙酯 、 (2R)-tetrahydrofuran-2-carbonyl chloride 在 正丁基锂 作用下， 以 四氢呋喃 、 hexanes 为溶剂， 反应 1.0h， 以100%的产率得到ethyl 3-oxo-3-[(2R)-tetrahydrofuran-2-yl]propanoate
  参考文献：
  名称：

  [EN] 2 -AMINOPYRIMIDINE DERIVATIVES AS HISTAMINE H4 ANTAGONISTS
  [FR] DÉRIVÉS DE 2-AMINOPYRIMIDINE COMME ANTAGONISTES DES RÉCEPTEURS H4 DE L'HISTAMINE

  摘要：

  式I的2-氨基嘧啶衍生物，其中不同取代基的含义如描述中所示。这些化合物可用作组胺受体H4拮抗剂。

  公开号：

  WO2009077608A1

文献信息

• Optimization of Brain Penetrant 11β-Hydroxysteroid Dehydrogenase Type I Inhibitors and in Vivo Testing in Diet-Induced Obese Mice
  作者：Frederick W. Goldberg、Alexander G. Dossetter、James S. Scott、Graeme R. Robb、Scott Boyd、Sam D. Groombridge、Paul D. Kemmitt、Tove Sjögren、Pablo Morentin Gutierrez、Joanne deSchoolmeester、John G. Swales、Andrew V. Turnbull、Martin J. Wild

  DOI：10.1021/jm4016729

  日期：2014.2.13

  11 beta-Hydroxysteroid dehydrogenase type 1 (11 beta-HSD1) has been widely considered by the pharmaceutical industry as a target to treat metabolic syndrome in type II diabetics. We hypothesized that central nervous system (CNS) penetration might be required to see efficacy. Starting from a previously reported pyrimidine compound, we removed hydrogen-bond donors to yield 3, which had modest CNS penetration. More significant progress was achieved by changing the core to give 40, which combines good potency and CNS penetration. Compound 40 was dosed to diet-induced obese (DIO) mice and gave excellent target engagement in the liver and high free exposures of drug, both peripherally and in the CNS. However, no body weight reduction or effects on glucose or insulin were observed in this model. Similar data were obtained with a structurally diverse thiazole compound 51. This work casts doubt on the hypothesis that localized tissue modulation of 11 beta-HSD1 activity alleviates metabolic syndrome.
• [EN] 2 -AMINOPYRIMIDINE DERIVATIVES AS HISTAMINE H4 ANTAGONISTS<br/>[FR] DÉRIVÉS DE 2-AMINOPYRIMIDINE COMME ANTAGONISTES DES RÉCEPTEURS H4 DE L'HISTAMINE
  申请人：PALAU PHARMA SA

  公开号：WO2009077608A1

  公开（公告）日：2009-06-25

  2-Amino-pyrimidine derivatives of formula I, wherein the meaning of the different substituents are those indicated in the description. These compounds are useful as histamine receptor H4 antagonists.

  式I的2-氨基嘧啶衍生物，其中不同取代基的含义如描述中所示。这些化合物可用作组胺受体H4拮抗剂。