| 1350723-05-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• CAS: 1350723-05-5
• 化学式: C₁₁H₇ClFNOS
• 分子量: 255.7
• InChiKey: FNBUIAUIXLHKIZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.64
• 重原子数：
  16.0
• 可旋转键数：
  2.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  29.96
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  4-amino-5-[2,4-bis(benzyloxy)-5-isopropylphenyl]isoxazole-3-carboxylic acid ethylamide 、 在 三氯化硼 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 6.17h， 生成 5-[2,4-dihydroxy-5-(prop-2-yl)phenyl]-N-ethyl-4-({[5-(4-fluorophenyl)-4-methyl-1,3-thiazol-2-yl]carbonyl}amino)isoxazole-3-carboxamide
  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