5-(2,4-bis(benzyloxy)-5-chlorophenyl)-2H-pyrazole-3-carboxylic acid ethyl ester | 1001385-35-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 5-(2,4-bis(benzyloxy)-5-chlorophenyl)-2H-pyrazole-3-carboxylic acid ethyl ester
• 英文别名: ethyl 3-[5-chloro-2,4-bis(phenylmethoxy)phenyl]-1H-pyrazole-5-carboxylate
• CAS: 1001385-35-8
• 化学式: C₂₆H₂₃ClN₂O₄
• 分子量: 462.933
• InChiKey: PZQBWDHVMNICRU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  33
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  73.4
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-(2,4-bis(benzyloxy)-5-chlorophenyl)-2H-pyrazole-3-carboxylic acid ethyl ester 在 N-碘代丁二酰亚胺 、 ammonium cerium(IV) nitrate 作用下， 以 乙腈 为溶剂， 以98%的产率得到5-(2,4-bis(benzyloxy)-5-chlorophenyl)-4-iodo-2H-pyrazole-3-carboxylic acid ethyl ester
  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
• 作为产物：
  描述：

  4-(2,4-bis(benzyloxy)-5-chlorophenyl)-2-hydroxy-4-oxobut-2-enoic acid ethyl ester 在 盐酸肼 作用下， 以 乙醇 为溶剂， 反应 3.75h， 以87%的产率得到5-(2,4-bis(benzyloxy)-5-chlorophenyl)-2H-pyrazole-3-carboxylic acid ethyl ester
  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