2-benzyl-3-ethoxy-2-hydroxy-3-oxopropanoic acid | 252730-57-7

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 苯丙酸
• 英文名称: 2-benzyl-3-ethoxy-2-hydroxy-3-oxopropanoic acid
• CAS: 252730-57-7
• 化学式: C₁₂H₁₄O₅
• 分子量: 238.24
• InChiKey: HOSNVJQPMAOZEN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  17
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  83.8
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-benzyl-3-ethoxy-2-hydroxy-3-oxopropanoic acid 170.0 ℃ 、2.0 kPa 条件下， 反应 3.0h， 生成 2-羟基-3-苯基丙酸乙酯
  参考文献：
  名称：

  Mild air-oxidation of 1,3-dicarbonyl compounds with cesium salts: Novel α-hydroxylation accompanied by partial hydrolysis of malonate derivatives

  摘要：

  13-Dicarbonyl compounds (1) were: efficiently oxygenated at the alpha-position with cesium salts, such as CsF or Cs2CO3 (0.1 Meq) in DMF at room temperature. Reaction of malonate derivatives (1a, b) with excess amount (2 Meg) of Cs2CO3 gave alpha-hydroxylmonoester (3) formed by oxygenation and partial hydrolysis, which was decarboxylated to a lactic acid derivative (5). (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4039(99)01618-4
• 作为产物：
  描述：

  苄基丙二酸二乙酯 在 cesium fluoride 、 potassium hydroxide 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 72.0h， 生成 2-benzyl-3-ethoxy-2-hydroxy-3-oxopropanoic acid
  参考文献：
  名称：

  发现新的恶唑烷二酮衍生物作为有效的和选择性的盐皮质激素受体拮抗剂

  摘要：

  新颖恶唑烷二酮类似物被发现为有效的和选择性盐皮质激素受体（MR）拮抗剂。结构-活性关系（SAR）研究的重点是提高效力和微粒体的稳定性。选定的化合物表现出出色的MR活性，合理的核激素受体选择性和可接受的大鼠药代动力学。

  DOI：

  10.1016/j.bmcl.2013.05.077

文献信息

• Discovery of Benzimidazole Oxazolidinediones as Novel and Selective Nonsteroidal Mineralocorticoid Receptor Antagonists
  作者：Christine Yang、Jaume Balsells、Hong D. Chu、Jason M. Cox、Alejandro Crespo、Xiuying Ma、Lisa Contino、Patricia Brown、Sheng Gao、Beata Zamlynny、Judyann Wiltsie、Joseph Clemas、JeanMarie Lisnock、Jack Gibson、Gaochao Zhou、Margarita Garcia-Calvo、Thomas J. Bateman、Vincent Tong、Ling Xu、Martin Crook、Peter Sinclair、Hong C. Shen

  DOI：10.1021/acsmedchemlett.5b00010

  日期：2015.4.9

  Elaboration of the oxazolidinedione series led to replacement of the exocyclic amides with substituted benzimidazoles. The structure-activity relationship (SAR) exploration resulted in the discovery of potent and selective nonsteroidal mineralocorticoid receptor (MR) antagonists with significantly improved microsomal stability and pharmacokinetic (PK) profile relative to the HTS hit 1a. One compound

  恶唑烷二酮系列的精制导致取代的苯并咪唑取代了环外酰胺。构效关系（SAR）的探索导致发现了一种有效的和选择性的非甾体盐皮质激素受体（MR）拮抗剂，相对于HTS 1a而言，它们具有明显改善的微粒体稳定性和药代动力学（PK）谱。在大鼠钠尿症模型中，一种化合物2p在100 mg / kg（po）时具有与螺内酯（SPL）相当的功效。因此，该系列被确认为进一步优化的潜在系列。
• [EN] MINERALOCORTICOID RECEPTOR ANTAGONISTS<br/>[FR] ANTAGONISTES D'UN RÉCEPTEUR DES MINÉRALOCORTICOÏDES
  申请人：MERCK SHARP & DOHME

  公开号：WO2013055607A1

  公开（公告）日：2013-04-18

  The present invention is directed to compounds of the Formula (I) as well as pharmaceutically acceptable salts thereof, that are aldosterone receptor antagonists which might be useful for treating aldosterone-mediated diseases. The invention furthermore relates to processes for preparing compounds of the Formula (I), to their possible use for the treatment of the abovementioned diseases and for preparing pharmaceuticals for this purpose, and to pharmaceutical compositions which comprise compounds of the Formula (I).

  本发明涉及式(I)的化合物以及其药用盐，这些化合物是醛固酮受体拮抗剂，可能对治疗醛固酮介导的疾病有用。该发明还涉及制备式(I)化合物的方法，以及它们可能用于治疗上述疾病和制备用于此目的的药物的方法，以及包括式(I)化合物的药物组合物。
• [EN] MINERALOCORTICOID RECEPTOR ANTAGONISTS<br/>[FR] ANTAGONISTES DE RÉCEPTEUR DES MINÉRALOCORTICOÏDES
  申请人：MERCK SHARP & DOHME

  公开号：WO2013055606A1

  公开（公告）日：2013-04-18

  The present invention is directed to compounds of the Formula (I) as well as pharmaceutically acceptable salts thereof, that are potentially useful for treating aldosterone-mediated diseases. The invention furthermore relates to processes for preparing compounds of the Formula (I), to their possible use in the treatment of the above mentioned diseases and for preparing pharmaceuticals for this purpose, and to pharmaceutical compositions which comprise compounds of the Formula (I).

  本发明涉及式（I）的化合物及其药学上可接受的盐，这些化合物可能有用于治疗醛固酮介导的疾病。本发明还涉及制备式（I）的化合物的过程，以及它们在治疗上述疾病和制备药物目的中的可能用途，以及包括式（I）的化合物的药物组合物。
• Mineralocorticoid receptor antagonists
  申请人：Merck Sharp & Dohme Corp.

  公开号：US09085568B2

  公开（公告）日：2015-07-21

  The present invention is directed to compounds of the Formula (I) as well as pharmaceutically acceptable salts thereof that are possible useful for treating aldosterone-mediated diseases. The invention furthermore relates to processes for preparing compounds of the Formula (I), to their possible use for the treatment of the above mentioned diseases and for preparing pharmaceuticals for this purpose, and to pharmaceutical compositions which comprise compounds of the Formula (I).

  本发明涉及公式（I）的化合物及其药学上可接受的盐，这些化合物可能有用于治疗醛固酮介导的疾病。此外，本发明还涉及制备公式（I）化合物的过程，以及它们可能用于治疗上述疾病和制备用于此目的的药物，并且涉及包含公式（I）化合物的制药组合物。
• MINERALOCORTICOID RECEPTOR ANTAGONISTS
  申请人：MERCK SHARP & DOHME CORP.

  公开号：US20150166490A1

  公开（公告）日：2015-06-18

  The present invention is directed to compounds of the Formula I as well as pharmaceutically acceptable salts thereof, that are potentially useful for treating aldosterone-mediated diseases. The invention furthermore relates to processes for preparing compounds of the Formula I, to their possible use in the treatment of the abovementioned diseases and for preparing pharmaceuticals for this purpose, and to pharmaceutical compositions which comprise compounds of the Formula I.

  本发明涉及式I化合物及其药学上可接受的盐，这些化合物可能有助于治疗醛固酮介导的疾病。此外，本发明还涉及制备式I化合物的方法，其可能用于治疗上述疾病和制备药物，以及包含式I化合物的药物组合物。