5-(2,4-dihydroxy-5-isopropylphenyl)-4-[4-(4-methylpiperazin-1-yl)benzoylamino]isoxazole-3-carboxylic acid ethylamide trifluoroacetate | 1350722-62-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 5-(2,4-dihydroxy-5-isopropylphenyl)-4-[4-(4-methylpiperazin-1-yl)benzoylamino]isoxazole-3-carboxylic acid ethylamide trifluoroacetate
• CAS: 1350722-62-1
• 化学式: C₂HF₃O₂*C₂₇H₃₃N₅O₅
• 分子量: 621.613
• InChiKey: HDQJMPJQJIVQIT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.26
• 重原子数：
  44.0
• 可旋转键数：
  7.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  168.47
• 氢给体数：
  5.0
• 氢受体数：
  9.0

反应信息

• 作为产物：
  描述：

  5-(2,4-双(苄氧基)-5-异丙基苯基)-n-乙基异噁唑-3-羧酰胺 在 水 、 硝酸 、 乙酸酐 、 三氯化硼 、 氯化铵 、 三乙胺 、 锌 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 76.92h， 生成 5-(2,4-dihydroxy-5-isopropylphenyl)-4-[4-(4-methylpiperazin-1-yl)benzoylamino]isoxazole-3-carboxylic acid ethylamide trifluoroacetate
  参考文献：
  名称：

  Novel 3,4-Isoxazolediamides as Potent Inhibitors of Chaperone Heat Shock Protein 90

  摘要：

  A structural investigation on the isoxazole scaffold led to the discovery of 3,4-isoxazolediamide compounds endowed with potent Hsp90 inhibitory properties. We have found that compounds possessing a nitrogen atom directly attached to the C-4 heterocycle ring possess in vitro Hsp90 inhibitory properties at least comparable to those of the structurally related 4,S-diarylisoxazole derivatives. A group of compounds from this series of diamides combine potent binding affinity and cell growth inhibitory activity in both series of alkyl- and aryl- or heteroarylarnides, with IC50 in the low nanomolar range. The 3,4-isoxazolediamides were also very effective in causing dramatic depletion of the examined client proteins and, as expected for the Hsp90 inhibitors, always induced a very strong increase in the expression levels of the chaperone Hsp70. In vivo studies against human epidermoid carcinoma A431 showed an antitumor effect of morpholine derivative 73 comparable to that induced by the reference compound 10.

  DOI：

  10.1021/jm201155e