4-(cyclohexylethynyl)-5-(2,4-dihydroxy-5-isopropyl-phenyl)-N-ethyl-isoxazole-3-carboxamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-(cyclohexylethynyl)-5-(2,4-dihydroxy-5-isopropyl-phenyl)-N-ethyl-isoxazole-3-carboxamide
• 英文别名: 4-(2-cyclohexylethynyl)-5-(2,4-dihydroxy-5-propan-2-ylphenyl)-N-ethyl-1,2-oxazole-3-carboxamide
• 化学式: C₂₃H₂₈N₂O₄
• 分子量: 396.486
• InChiKey: BLWOIFSJVMHKAM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  95.6
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-乙酰基-6-异丙基-1,3-苯二酚 在 bis-triphenylphosphine-palladium(II) chloride 、 N-碘代丁二酰亚胺 、 copper(l) iodide 、 ammonium cerium (IV) nitrate 、 盐酸羟胺 、 sodium ethanolate 、 三溴化硼 、 potassium carbonate 作用下， 以 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 18.17h， 生成 4-(cyclohexylethynyl)-5-(2,4-dihydroxy-5-isopropyl-phenyl)-N-ethyl-isoxazole-3-carboxamide
  参考文献：
  名称：

  Synthesis and biological evaluation of 3,5-disubstituted-4-alkynylisoxozales as a novel class of HSP90 inhibitors

  摘要：

  A series of 3,5-disubstitute-4-alkynylisoxazole derivatives were designed and synthesized through palladium(II)-copper(I) catalyzed Sonogashira cross-coupling reaction of an alkynyl moiety and an isoxazole scaffold as novel HSP90 inhibitors. The resultant compounds displayed moderate to potent binding affinity to HSP90 proteins, and also demonstrated good cell growth inhibitory activity against various cancer cell lines (A549, K562, MCF-7, DU145 and Hela). Some compounds (18d, 18e, 19a, 19d, 20c and 20q) show similar or better binding affinity towards HSP90a and HSP90b comparing to NVP-AUY922. In addition, compounds 18e, 19a and 20q exhibited potent inhibitory activity against various human cancer cell lines. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.06.009

文献信息

• Synthesis and biological evaluation of 3,5-disubstituted-4-alkynylisoxozales as a novel class of HSP90 inhibitors
  作者：Jian Sun、Cai Lin、Xiaochu Qin、Xiaoping Dong、Zhengchao Tu、Fei Tang、Chaonan Chen、Jiancun Zhang

  DOI：10.1016/j.bmcl.2015.06.009

  日期：2015.8

  A series of 3,5-disubstitute-4-alkynylisoxazole derivatives were designed and synthesized through palladium(II)-copper(I) catalyzed Sonogashira cross-coupling reaction of an alkynyl moiety and an isoxazole scaffold as novel HSP90 inhibitors. The resultant compounds displayed moderate to potent binding affinity to HSP90 proteins, and also demonstrated good cell growth inhibitory activity against various cancer cell lines (A549, K562, MCF-7, DU145 and Hela). Some compounds (18d, 18e, 19a, 19d, 20c and 20q) show similar or better binding affinity towards HSP90a and HSP90b comparing to NVP-AUY922. In addition, compounds 18e, 19a and 20q exhibited potent inhibitory activity against various human cancer cell lines. (C) 2015 Elsevier Ltd. All rights reserved.