3-(5-chloro-2,4-dihydroxyphenyl)-N-ethyl-4-{3-[({[2-(trifluoromethyl)phenyl]methyl}amino)methyl]phenyl}-1H-pyrazole-5-carboxamide | 1001385-44-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 3-(5-chloro-2,4-dihydroxyphenyl)-N-ethyl-4-{3-[({[2-(trifluoromethyl)phenyl]methyl}amino)methyl]phenyl}-1H-pyrazole-5-carboxamide
• 英文别名: 3-(5-chloro-2,4-dihydroxyphenyl)-N-ethyl-4-[3-[[[2-(trifluoromethyl)phenyl]methylamino]methyl]phenyl]-1H-pyrazole-5-carboxamide
• CAS: 1001385-44-9
• 化学式: C₂₇H₂₄ClF₃N₄O₃
• 分子量: 544.961
• InChiKey: ZTEUZIUQSSFLER-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  38
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  110
• 氢给体数：
  5
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  在 palladium on activated charcoal 氢气 、 溶剂黄146 作用下， 反应 16.0h， 生成 3-(5-chloro-2,4-dihydroxyphenyl)-N-ethyl-4-{3-[({[2-(trifluoromethyl)phenyl]methyl}amino)methyl]phenyl}-1H-pyrazole-5-carboxamide
  参考文献：
  名称：

  4,5-Diarylisoxazole Hsp90 Chaperone Inhibitors: Potential Therapeutic Agents for the Treatment of Cancer

  摘要：

  Inhibitors of the Hsp90 molecular chaperone are showing considerable promise as potential chemotherapeutic agents for cancer. Here, we describe the structure-based design, synthesis, structure-activity relationships and pharmacokinetics of potent small-molecule inhibitors of Hsp90 based on the 4,5-diarylisoxazole scaffold. Analogues from this series have high affinity for Hsp90, as measured in a fluorescence polarization (FP) competitive binding assay, and are active in cancer cell lines where they inhibit proliferation and exhibit a characteristic profile of depletion of oncogenic proteins and concomitant elevation of Hsp72. Compound 40f (VER-52296/NVP-AUY922) is potent in the Hsp90 FP binding assay (IC50 = 21 nM) and inhibits proliferation of various human cancer cell lines in vitro, with GI50 averaging 9 nM. Compound 40f is retained in tumors in vivo when administered i.p., as evaluated by cassette dosing in tumor-bearing mice. In a human colon cancer xenograft model, 40f inhibits tumor growth by approximately 50%.

  DOI：

  10.1021/jm701018h