N-(4-苯甲酰基苯基)-3,3,3-三氟-2-羟基-2-甲基丙酰胺 | 147696-09-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: N-(4-苯甲酰基苯基)-3,3,3-三氟-2-羟基-2-甲基丙酰胺
• 英文名称: (+/-)-ZD6169
• 英文别名: N-(4-benzoylphenyl)-3,3,3-trifluoro-2-hydroxy-2-methylpropionamide；ZM240392；racemic ZD6169；N-[4-(Phenylcarbonyl)phenyl]-3,3,3-trifluoro-2-hydroxy-2-methylpropanamide；N-(4-benzoylphenyl)-3,3,3-trifluoro-2-hydroxy-2-methylpropanamide
• CAS: 147696-09-1
• 化学式: C₁₇H₁₄F₃NO₃
• 分子量: 337.298
• InChiKey: LVEDGSIMCSQNNX-UHFFFAOYSA-N

物化性质

• 沸点：
  514.0±50.0 °C(Predicted)
• 密度：
  1.362±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 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：

  N-(4-苯甲酰基苯基)-3,3,3-三氟-2-羟基-2-甲基丙酰胺 在 sodium tetrahydroborate 作用下， 以75%的产率得到3,3,3-trifluoro-2-hydroxy-N-[4-[hydroxy(phenyl)methyl]phenyl]-2-methylpropanamide
  参考文献：
  名称：

  N-Aryl-3,3,3-trifluoro-2-hydroxy-2-methylpropanamides:  K_ATP Potassium Channel Openers. Modifications on the Western Region

  摘要：

  A subset of antiandrogen compounds, the N-aryl-3,3,3-trinuoro-2-hydroxy-2-methylpropanamides 1, were found to activate ATP sensitive potassium channels (K-ATP) and represent a new class of potassium channel openers (PCOs). A structure-activity relationship was carried out on the western region of this series with the goal of obtaining an activator of the ATP sensitive potassium channel suitable for use in the treatment of urge urinary incontinence. In particular three large 4-(N-aryl) substituents, the (N-phenyl-N-methylamino)sulfonyl, benzoyl, and 4-pyridylsulfonyl moieties, yielded non-antiandrogen, K-ATP potassium channel openers (39, 41, and 64, respectively) that are bladder selective in an in vivo rat model that simultaneously measures bladder contractions, heart rate, and blood pressure. Substitutions of the aryl rings of 41 and 64 gave several derivatives that also display selectivity in the in vivo rat model; however, none appear to offer a substantial advantage over 41 and 64. The PCO activity of 41 and 64 resides in the (S)-(-) enantiomers. ZD6169, 41(S), has been selected into development for the treatment of urge urinary incontinence.

  DOI：

  10.1021/jm960365n
• 作为产物：
  描述：

  4-氨基二苯甲酮 、 R/S-3,3,3-trifluoro-2-hydroxy-2-methylproanoyl chloride 以 N,N-二甲基乙酰胺 为溶剂， 反应 1.5h， 生成 N-(4-苯甲酰基苯基)-3,3,3-三氟-2-羟基-2-甲基丙酰胺
  参考文献：
  名称：

  （R）-三氟-2-羟基-2-甲基丙酸的酸酐作为丙酮酸脱氢酶激酶的抑制剂。

  摘要：

  描述了从N-苯基-3,3开始优化一系列作为丙酮酸脱氢酶激酶（PDHK）抑制剂的（R）-3,3，3-三氟-2-羟基-2-甲基丙酸的苯胺衍生物，3-三氟-2-羟基-2-甲基丙酰胺1（IC（50）= 35 +/- 1.4 microM）。已经发现，在苯胺的邻位上的小的吸电子基团，即氯，乙酰基或溴，增加了20-40倍的效力。当苯胺在4位被吸电子基团（即羧基，羧酰胺和亚磺酰胺）取代时，该系列化合物的口服生物利用度最佳（通过AUC测定）。N-（2-氯-4-异丁基氨磺酰基苯基）-（R）-3,3,3-三氟-2-羟基-2-甲基丙酰胺（10a）在主酶分析中抑制PDHK，IC（50）为13 + /-1.5 nM，增强人成纤维细胞中[[14] C]乳酸盐氧化成（14）CO（2）的活性，口服剂量低至30 micromol / kg后2.5和5 h显着降低血液乳酸水平，并增加肌肉，肾脏，肝脏和心脏组织中的PDH。但是

  DOI：

  10.1021/jm0000923

文献信息

• Therapeutic amides
  申请人：Imperial Chemical Industries PLC

  公开号：US05272163A1

  公开（公告）日：1993-12-21

  Amides having formula I: ##STR1## wherein E, X, R.sup.2 and R.sup.3 have the meanings given in the specification, and pharmaceutically acceptable salts and pharmaceutically acceptable in vivo hydrolysable esters thereof, which are useful in the treatment of urinary incontinence. Further provided are processes for preparing the amides and pharmaceutical compositions containing them.

  酰胺具有以下化学式I：##STR1## 其中E、X、R.sup.2和R.sup.3的含义如规范中所述，并且其药学上可接受的盐和在体内可水解的酯，可用于治疗尿失禁。还提供了制备这些酰胺的方法和含有它们的药物组合物。
• TRAUMA THERAPY
  申请人：Dobson Geoffrey Philip

  公开号：US20090324748A1

  公开（公告）日：2009-12-31

  The invention provides a method of reducing injury to cells, tissues or organs of a body following trauma by administering a composition to the body following trauma, including: (i) a potassium channel opener or agonist and/or an adenosine receptor agonist; and (ii) a local anaesthetic. Also provided is a composition for reducing injury to cells, tissues or organs of a body following trauma including: (i) and (ii). The composition may be hypertonic.

  本发明提供了一种减少创伤后身体细胞、组织或器官受损的方法，包括在创伤后向身体注射一种组合物，其中包括：（i）一个钾通道开放剂或激动剂和/或腺苷受体激动剂；和（ii）一个局部麻醉剂。同时提供了一种用于减少创伤后身体细胞、组织或器官受损的组合物，包括（i）和（ii）。该组合物可以是高渗的。
• Enzymatic process for stereoselective preparation of a tertiary acid
  申请人：Zeneca LTD

  公开号：US06261830B1

  公开（公告）日：2001-07-17

  An enzymatic process for preparing amides of Formula I wherein X, E and * have the meanings defined in the specification. Chiral intermediates useful for preparing compound of Formula I and enzymatic processes for preparing such chiral intermediates are also described.

  一种用于制备公式I中的酰胺的酶促过程，其中X，E和*具有规范中定义的含义。还描述了用于制备公式I化合物的手性中间体以及制备这种手性中间体的酶促过程。
• Enzymatic process for stereoselective preparation of a tertiary alcohol
  申请人：Zeneca Limited

  公开号：US06110729A1

  公开（公告）日：2000-08-29

  A stereoselective method for making compounds of Formula VIII ##STR1## wherein A and * are as defined in the specification. Enzymic processes and intermediates useful for preparing compound of Formula VIII are disclosed.

  一种立体选择性的制备化合物VIII的方法，其中公式中的A和*如规范中所定义。揭示了用于制备化合物VIII的酶法过程和中间体。
• Improved tissue maintenance
  申请人：Hibernation Therapeutics Limited

  公开号：EP2471360A1

  公开（公告）日：2012-07-04

  The invention provides a method of reducing damage to a tissue, organ or cell from surgical procedures comprising administering a composition comprising a potassium channel opener/agonist and/or an adenosine receptor agonist (eg. adenosine) together with a local anaesthetic (eg. lignocaine) when perfusing the organ.

  本发明提供了一种减少外科手术对组织、器官或细胞的损伤的方法，包括在灌注器官时施用一种组合物，该组合物包含钾离子通道开启剂/激动剂和/或腺苷受体激动剂（如腺苷）以及局麻药（如木质素）。