[5-Acetyloxy-4-[4-(ethylcarbamoyl)-5-[4-(morpholin-4-ylmethyl)phenyl]triazol-1-yl]-2-propan-2-ylphenyl] acetate | 1581709-48-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: [5-Acetyloxy-4-[4-(ethylcarbamoyl)-5-[4-(morpholin-4-ylmethyl)phenyl]triazol-1-yl]-2-propan-2-ylphenyl] acetate
• 英文别名: [5-acetyloxy-4-[4-(ethylcarbamoyl)-5-[4-(morpholin-4-ylmethyl)phenyl]triazol-1-yl]-2-propan-2-ylphenyl] acetate
• CAS: 1581709-48-9
• 化学式: C₂₉H₃₅N₅O₆
• 分子量: 549.627
• InChiKey: HMMYGAXNBUZCKY-UHFFFAOYSA-N

物化性质

• 密度：
  1.28±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  40
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  125
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  1-(2,4-bis-benzyloxy-5-isopropyl-phenyl)-5-(4-methanesulfonyloxy-methyl-phenyl)-1H-[1,2,3]triazole-4-carboxylic acid methyl ester 在 10 wt% Pd(OH)2 on carbon 、 氢气 、 三乙胺 作用下， 以 甲醇 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 20.0~80.0 ℃ 、101.33 kPa 条件下， 反应 24.0h， 生成 [5-Acetyloxy-4-[4-(ethylcarbamoyl)-5-[4-(morpholin-4-ylmethyl)phenyl]triazol-1-yl]-2-propan-2-ylphenyl] acetate
  参考文献：
  名称：

  Synthesis and Evaluation of New Hsp90 Inhibitors Based on a 1,4,5-Trisubstituted 1,2,3-Triazole Scaffold

  摘要：

  Ruthenium catalyzed 1,3-cycloaddition (click chemistry) of an azido moiety installed on dihydroxycumene scaffold with differently substituted aryl propiolates gave a new family of 1,4,5-trisubstituted triazole carboxylic acid derivatives that showed high affinity toward Hsp90 associated with cell proliferation inhibition, both in nanomolar range. The 1,5 arrangement of the resorcinol, the aryl moieties, and the presence of an alkyl (secondary) amide in position 4 of the triazole ring were essential to get high activity. Docking simulations suggested that the triazoles penetrate the Hsp90 ATP binding site. Some 1,4,5-trisubstituted triazole carboxamides induced dramatic depletion of the examined client proteins and a very strong increase in the expression levels of the chaperone Hsp70. In vitro metabolic stability and in vivo preliminary studies on selected compounds have shown promising results comparable to the potent Hsp90 inhibitor NVP-AUY922. One of them, (compound 18, SST0287CL1) was selected for further investigation as the most promising drug candidate.

  DOI：

  10.1021/jm401536b