methyl 4-{5-(4-chlorophenyl)-1,3,4-oxadiazol-2-yl}benzoate | 1173178-66-9

• 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: methyl 4-{5-(4-chlorophenyl)-1,3,4-oxadiazol-2-yl}benzoate
• CAS: 1173178-66-9
• 化学式: C₁₆H₁₁ClN₂O₃
• 分子量: 314.728
• InChiKey: GCGDPDIWULJNLS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.84
• 重原子数：
  22.0
• 可旋转键数：
  3.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  65.22
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  methyl 4-{5-(4-chlorophenyl)-1,3,4-oxadiazol-2-yl}benzoate 在 草酰氯 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 水 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.17h， 生成 4-(5-(4-chlorophenyl)-1,3,4-oxadiazol-2-yl)benzamide
  参考文献：
  名称：

  From Sphingosine Kinase to Dihydroceramide Desaturase: A Structure–Activity Relationship (SAR) Study of the Enzyme Inhibitory and Anticancer Activity of 4-((4-(4-Chlorophenyl)thiazol-2-yl)amino)phenol (SKI-II)

  摘要：

  The sphingosine kinase (SK) inhibitor, SKI-II, has been employed extensively in biological investigations of the role of SK1 and SK2 in disease and has demonstrated impressive anticancer activity in vitro and in vivo. However, interpretations of results using this pharmacological agent are complicated by several factors: poor SK1/2 selectivity, additional activity as an inducer of SK1-degradation, and off-target effects, including its recently identified capacity to inhibit dihydroceramide desaturase-1 (Des1). In this study, we have delineated the structure-activity relationship (SAR) for these different targets and correlated them to that required for anticancer activity and determined that Des1 inhibition is primarily responsible for the antiproliferative effects of SKI-II and its analogues. In the course of these efforts, a series of novel SK1, SK2, and Des1 inhibitors have been generated, including compounds with significantly greater anticancer activity.

  DOI：

  10.1021/acs.jmedchem.5b01439
• 作为产物：
  描述：

  对苯二甲酸单甲酯 在 草酰氯 、 三氯氧磷 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 22.0h， 生成 methyl 4-{5-(4-chlorophenyl)-1,3,4-oxadiazol-2-yl}benzoate
  参考文献：
  名称：

  From Sphingosine Kinase to Dihydroceramide Desaturase: A Structure–Activity Relationship (SAR) Study of the Enzyme Inhibitory and Anticancer Activity of 4-((4-(4-Chlorophenyl)thiazol-2-yl)amino)phenol (SKI-II)

  摘要：

  The sphingosine kinase (SK) inhibitor, SKI-II, has been employed extensively in biological investigations of the role of SK1 and SK2 in disease and has demonstrated impressive anticancer activity in vitro and in vivo. However, interpretations of results using this pharmacological agent are complicated by several factors: poor SK1/2 selectivity, additional activity as an inducer of SK1-degradation, and off-target effects, including its recently identified capacity to inhibit dihydroceramide desaturase-1 (Des1). In this study, we have delineated the structure-activity relationship (SAR) for these different targets and correlated them to that required for anticancer activity and determined that Des1 inhibition is primarily responsible for the antiproliferative effects of SKI-II and its analogues. In the course of these efforts, a series of novel SK1, SK2, and Des1 inhibitors have been generated, including compounds with significantly greater anticancer activity.

  DOI：

  10.1021/acs.jmedchem.5b01439

文献信息

• Copper-Mediated Direct Arylation of 1,3,4-Oxadiazoles and 1,2,4-Triazoles with Aryl Iodides
  作者：Tsuyoshi Kawano、Tomoki Yoshizumi、Koji Hirano、Tetsuya Satoh、Masahiro Miura

  DOI：10.1021/ol9011212

  日期：2009.7.16

  The copper-mediated direct arylation of 1,3,4-oxadiazoles and 1,2,4-triazoles with aryl iodides proceeds efficiently in the presence of suitable ligands and bases. This method allows the installation of a variety of aryl moieties bearing a functional group such as ketone, ester, or nitrile so as to enable the facile construction of various functionalized oxadiazole and triazole core π systems.

  在合适的配体和碱的存在下，铜介导的1,3,4-恶二唑和1,2,4-三唑与芳基碘的直接芳基化反应有效进行。该方法允许安装带有诸如酮，酯或腈之类的官能团的各种芳基部分，从而使得能够容易地构建各种官能化的恶二唑和三唑核π系统。