3-(3,4-dihydroxyphenyl)-4,5-dihydronaphtho[2,1-d]isoxazole-7,8-diol | 1615715-47-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 3-(3,4-dihydroxyphenyl)-4,5-dihydronaphtho[2,1-d]isoxazole-7,8-diol
• 英文别名: 3-(3,4-Dihydroxyphenyl)-4,5-dihydrobenzo[g][1,2]benzoxazole-7,8-diol；3-(3,4-dihydroxyphenyl)-4,5-dihydrobenzo[g][1,2]benzoxazole-7,8-diol
• CAS: 1615715-47-3
• 化学式: C₁₇H₁₃NO₅
• 分子量: 311.294
• InChiKey: OOIMRSUYXKVJGR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  23
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  107
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  3,4-二甲氧基苯甲酰氯 在 三溴化硼 、 溶剂黄146 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 二氯甲烷 、 甲苯 为溶剂， 反应 18.3h， 生成 3-(3,4-dihydroxyphenyl)-4,5-dihydronaphtho[2,1-d]isoxazole-7,8-diol
  参考文献：
  名称：

  Antiproliferative novel isoxazoles: Modeling, virtual screening, synthesis, and bioactivity evaluation

  摘要：

  A series of novel isoxazole derivatives were efficiently synthesized through the adaptation/modification of an in situ synthetic procedure for pyrazoles. All novel compounds were tested against four different cell lines to evaluate their antiproliferative activity. Based on the Hela cells results of this study and previous work, a classification model to predict the anti-proliferative activity of isoxazole and pyrazole derivatives was developed. Random Forest modeling was used in view of the development of an accurate and reliable model that was subsequently validated. A virtual screening study was then proposed for the design of novel active derivatives. Compounds 9 and 11 demonstrated significant cytostatic activity; the fused isoxazole derivative 18 and the virtually proposed compound 2v, were proved at least 10 times more potent as compared to compound 9, with IC50 values near and below 1 mu M. In conclusion, a new series of isoxazoles was exploited with some of them exhibiting promising cytostatic activities. Further studies on the substitution pattern of the isoxazole core can potentially provide compounds with cytostatic action at the nM scale. In this direction the in silica approach described herein can also be used to screen existing databases to identify derivatives with anticipated activity. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.05.011

文献信息

• Antiproliferative novel isoxazoles: Modeling, virtual screening, synthesis, and bioactivity evaluation
  作者：Evangelia Tzanetou、Sandra Liekens、Konstantinos M. Kasiotis、Georgia Melagraki、Antreas Afantitis、Nikolas Fokialakis、Serkos A. Haroutounian

  DOI：10.1016/j.ejmech.2014.05.011

  日期：2014.6

  A series of novel isoxazole derivatives were efficiently synthesized through the adaptation/modification of an in situ synthetic procedure for pyrazoles. All novel compounds were tested against four different cell lines to evaluate their antiproliferative activity. Based on the Hela cells results of this study and previous work, a classification model to predict the anti-proliferative activity of isoxazole and pyrazole derivatives was developed. Random Forest modeling was used in view of the development of an accurate and reliable model that was subsequently validated. A virtual screening study was then proposed for the design of novel active derivatives. Compounds 9 and 11 demonstrated significant cytostatic activity; the fused isoxazole derivative 18 and the virtually proposed compound 2v, were proved at least 10 times more potent as compared to compound 9, with IC50 values near and below 1 mu M. In conclusion, a new series of isoxazoles was exploited with some of them exhibiting promising cytostatic activities. Further studies on the substitution pattern of the isoxazole core can potentially provide compounds with cytostatic action at the nM scale. In this direction the in silica approach described herein can also be used to screen existing databases to identify derivatives with anticipated activity. (C) 2014 Elsevier Masson SAS. All rights reserved.