(RS)-2-methyl-3-oxo-4,4,4-trifluorobutyrohydroxamic acid | 145433-08-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (RS)-2-methyl-3-oxo-4,4,4-trifluorobutyrohydroxamic acid
• 英文别名: 4,4,4-trifluoro-N-hydroxy-2-methyl-3-oxobutyramide；4,4,4-trifluoro-N-hydroxy-2-methyl-3-oxobutanamide
• CAS: 145433-08-5
• 化学式: C₅H₆F₃NO₃
• 分子量: 185.103
• InChiKey: RGUMFPDAYPXIFJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  66.4
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (RS)-2-methyl-3-oxo-4,4,4-trifluorobutyrohydroxamic acid 在 N-溴代丁二酰亚胺(NBS) 、 过氧化氢苯甲酰 、 硫酸 、 potassium carbonate 作用下， 以 四氯化碳 、 丙酮 为溶剂， 反应 26.0h， 生成 4-Bromomethyl-3-ethoxy-5-trifluoromethyl-isoxazole
  参考文献：
  名称：

  Synthesis and pharmacology of (RS)-2-amino-3-(3-hydroxy-5-trifluoromethyl-4-isoxazolyl)propionic acid, a potent AMPA receptor agonist

  摘要：

  Three isoxazole bioisosteres of glutamic acid derived from the specific AMPA receptor agonist (RS)-2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid (AMPA) were synthesized and tested electrophysiologically and in different receptor binding systems. (RS)-2-Amino-3-(3-hydroxy-5-trifluoromethyl-4-isoxazolyl)propionic acid (trifluoro-AMPA, 8) showed more potent agonist activity (EC50 2.3 muM) and lower affinity (IC50 0.08 muM) for AMPA receptors than AMPA itself (EC, 3.5 muM and IC50 0.04 muM, respectively). Like AMPA, trifluoro-AMPA (8) did not bind significantly to N-methyl-D-aspartic acid (NMDA) receptor sites, but trifluoro-AMPA (8) was more potent as an inhibitor of [H-3]kainic acid ([H-3]KAIN) binding (IC50 7.1 muM) than AMPA (IC50 32 muM). (RS)-2-Amino-3-(3-chloro-5-methyl-4-isoxazolyl)propionic acid (14), the 3-chloro analogue of AMPA, and the isomeric compound (RS)-2-amino-3-(3-chloro-4-methyl-5-isoxazolyl)propionic acid (15), did not show significant neuroexcitatory effects at or affinities for AMPA, NMDA, or KAIN receptor sites.

  DOI：

  10.1016/0223-5234(92)90181-y
• 作为产物：
  描述：

  2-甲基-4,4,4-三氟乙酰乙酸乙酯 在 sodium hydroxide 、 盐酸羟胺 作用下， 以 水 为溶剂， 反应 1.5h， 以61%的产率得到(RS)-2-methyl-3-oxo-4,4,4-trifluorobutyrohydroxamic acid
  参考文献：
  名称：

  [EN] BICYCLONONENE DERIVATIVES AS RENIN INHIBITORS
  [FR] DÉRIVÉS DU BICYCLONONÈNE EMPLOYÉS EN TANT QU'INHIBITEURS DE LA RÉNINE

  摘要：

  该发明涉及公式（I）的新型双环庚烯衍生物；以及其作为药物组合物中活性成分的用途。该发明还涉及相关方面，包括制备化合物的方法，含有其中一种或多种化合物的药物组合物，特别是它们作为肾素抑制剂的用途。

  公开号：

  WO2006021402A1

文献信息

• [EN] BICYCLONONENE DERIVATIVES AS RENIN INHIBITORS<br/>[FR] DÉRIVÉS DU BICYCLONONÈNE EMPLOYÉS EN TANT QU'INHIBITEURS DE LA RÉNINE
  申请人：ACTELION PHARMACEUTICALS LTD

  公开号：WO2006021402A1

  公开（公告）日：2006-03-02

  The invention relates to novel bicyclononene derivatives of Formula (I); and the use thereof as active ingredients in the preparation of pharmaceutical compositions. The invention also concerns related aspects including processes for the preparation of the compounds, pharmaceutical compositions containing one or more of those compounds and especially their use as inhibitors of renin.

  该发明涉及公式（I）的新型双环庚烯衍生物；以及其作为药物组合物中活性成分的用途。该发明还涉及相关方面，包括制备化合物的方法，含有其中一种或多种化合物的药物组合物，特别是它们作为肾素抑制剂的用途。
• Bicyclononene derivaties
  申请人：Bezencon Olivier

  公开号：US20090306123A1

  公开（公告）日：2009-12-10

  The invention relates to novel bicyclononene derivatives of Formula (I); and the use thereof as active ingredients in the preparation of pharmaceutical compositions. The invention also concerns related aspects including processes for the preparation of the compounds, pharmaceutical compositions containing one or more of those compounds and especially their use as inhibitors of renin.

  本发明涉及公式（I）的新型双环壬烯衍生物；以及将其作为制备药物组合物的活性成分的用途。本发明还涉及相关方面，包括制备化合物的过程，含有其中一种或多种化合物的药物组合物，特别是它们作为肾素抑制剂的用途。
• Bicyclononene derivatives
  申请人：Actelion Pharmaceuticals Ltd.

  公开号：US08138340B2

  公开（公告）日：2012-03-20

  The invention relates to novel bicyclononene derivatives of Formula (I); and the use thereof as active ingredients in the preparation of pharmaceutical compositions. The invention also concerns related aspects including processes for the preparation of the compounds, pharmaceutical compositions containing one or more of those compounds and especially their use as inhibitors of renin.

  本发明涉及公式（I）的新型双环壬烯衍生物，以及其作为制备药物组成部分的活性成分的用途。本发明还涉及相关方面，包括化合物的制备过程，含有其中一种或多种化合物的制药组合物，特别是它们作为肾素抑制剂的用途。
• Synthesis and pharmacology of (RS)-2-amino-3-(3-hydroxy-5-trifluoromethyl-4-isoxazolyl)propionic acid, a potent AMPA receptor agonist
  作者：U Madsen、B Ebert、P Krogsgaard-Larsen、EHF Wong

  DOI：10.1016/0223-5234(92)90181-y

  日期：1992.8

  Three isoxazole bioisosteres of glutamic acid derived from the specific AMPA receptor agonist (RS)-2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid (AMPA) were synthesized and tested electrophysiologically and in different receptor binding systems. (RS)-2-Amino-3-(3-hydroxy-5-trifluoromethyl-4-isoxazolyl)propionic acid (trifluoro-AMPA, 8) showed more potent agonist activity (EC50 2.3 muM) and lower affinity (IC50 0.08 muM) for AMPA receptors than AMPA itself (EC, 3.5 muM and IC50 0.04 muM, respectively). Like AMPA, trifluoro-AMPA (8) did not bind significantly to N-methyl-D-aspartic acid (NMDA) receptor sites, but trifluoro-AMPA (8) was more potent as an inhibitor of [H-3]kainic acid ([H-3]KAIN) binding (IC50 7.1 muM) than AMPA (IC50 32 muM). (RS)-2-Amino-3-(3-chloro-5-methyl-4-isoxazolyl)propionic acid (14), the 3-chloro analogue of AMPA, and the isomeric compound (RS)-2-amino-3-(3-chloro-4-methyl-5-isoxazolyl)propionic acid (15), did not show significant neuroexcitatory effects at or affinities for AMPA, NMDA, or KAIN receptor sites.