3-chloro-N-(2-prop-2-ynoxyphenyl)benzamide | 1610805-31-6

• 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: 3-chloro-N-(2-prop-2-ynoxyphenyl)benzamide
• CAS: 1610805-31-6
• 化学式: C₁₆H₁₂ClNO₂
• 分子量: 285.73
• InChiKey: CVRBJMIZEGGOBX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-chloro-N-(2-prop-2-ynoxyphenyl)benzamide 、 2-(4-azidophenethyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline 在 copper(II) sulfate 、 sodium ascorbate 作用下， 以 甲醇 、 水 为溶剂， 以62.2%的产率得到3-chloro-N-(2-((1-(4-(2-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)ethyl)phenyl)-1H-1,2,3-triazol-4-yl)methoxy)phenyl)benzamide
  参考文献：
  名称：

  Discovery of Novel P-Glycoprotein-Mediated Multidrug Resistance Inhibitors Bearing Triazole CoreviaClick Chemistry

  摘要：

  A novel series of P‐glycoprotein (P‐gp)‐mediated multidrug resistance (MDR) inhibitors bearing a triazol‐phenethyl‐tetrahydroisoquinoline scaffold were designed and synthesized via click chemistry. Most of the synthesized compounds showed higher reversal activity than verapamil (VRP). Among them, the most potent compound 5 showed a comparable activity with the known potent P‐gp inhibitor WK‐X‐34 with lower cytotoxicity (IC50s > 100 μm). Compared with VRP, compound 5 exhibited more potency in increasing drug accumulation in K562/A02 MDR cells. Moreover, compound 5 persisted longer chemo‐sensitizing effect (>24 h) than VRP (<6 h) with reversibility. Given the low intrinsic cytotoxicity and the potent reversal activity, compound 5 may represent a promising candidate for developing P‐gp‐mediated MDR inhibitor.

  DOI：

  10.1111/cbdd.12301
• 作为产物：
  描述：

  硝苯酚 在 铁粉 、 potassium carbonate 、 氯化铵 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 、 丙酮 为溶剂， 反应 30.5h， 生成 3-chloro-N-(2-prop-2-ynoxyphenyl)benzamide
  参考文献：
  名称：

  Discovery of Novel P-Glycoprotein-Mediated Multidrug Resistance Inhibitors Bearing Triazole CoreviaClick Chemistry

  摘要：

  A novel series of P‐glycoprotein (P‐gp)‐mediated multidrug resistance (MDR) inhibitors bearing a triazol‐phenethyl‐tetrahydroisoquinoline scaffold were designed and synthesized via click chemistry. Most of the synthesized compounds showed higher reversal activity than verapamil (VRP). Among them, the most potent compound 5 showed a comparable activity with the known potent P‐gp inhibitor WK‐X‐34 with lower cytotoxicity (IC50s > 100 μm). Compared with VRP, compound 5 exhibited more potency in increasing drug accumulation in K562/A02 MDR cells. Moreover, compound 5 persisted longer chemo‐sensitizing effect (>24 h) than VRP (<6 h) with reversibility. Given the low intrinsic cytotoxicity and the potent reversal activity, compound 5 may represent a promising candidate for developing P‐gp‐mediated MDR inhibitor.

  DOI：

  10.1111/cbdd.12301

文献信息

• Design, synthesis and evaluation of novel triazole core based P-glycoprotein-mediated multidrug resistance reversal agents
  作者：Lei Jiao、Qianqian Qiu、Baomin Liu、Tianxiao Zhao、Wenlong Huang、Hai Qian

  DOI：10.1016/j.bmc.2014.10.032

  日期：2014.12

  A novel series of triazol-N-ethyl-tetrahydroisoquinoline based compounds were designed and synthesized via click chemistry. Most of the synthesized compounds showed P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) reversal activities. Among them, compound 7 with little cytotoxicity towards GES-1 cells (IC50 > 80 mu M) and K562/A02 cells (IC50 > 80 mu M) exhibited more potency than verapamil (VRP) on increasing anticancer drug accumulation in K562/A02 cells. Moreover, compound 7 could significantly reverse MDR in a dose-dependent manner and also persist longer chemo-sensitizing effect than VRP with reversibility. Further mechanism studies revealed that compound 7 in reversing MDR revealed that it could remarkably increase the intracellular accumulation of both rhodamine-123 (Rh123) and adriamycin (ADM) in K562/A02 cells as well as inhibit their efflux from the cells. These results suggested that compound 7 showed more potency than the classical P-gp inhibitor VRP under the same conditions, which may be a promising P-gp-mediated MDR modulator for further development. (C) 2014 Elsevier Ltd. All rights reserved.