allyl 4-(2-(allyloxy)-2-oxoethyl)-2-amino-6-(3,5-dimethoxyphenyl)-4H-chromene-3-carboxylate | 1318165-60-4

• 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: allyl 4-(2-(allyloxy)-2-oxoethyl)-2-amino-6-(3,5-dimethoxyphenyl)-4H-chromene-3-carboxylate
• 英文别名: prop-2-enyl 2-amino-6-(3,5-dimethoxyphenyl)-4-(2-oxo-2-prop-2-enoxyethyl)-4H-chromene-3-carboxylate
• CAS: 1318165-60-4
• 化学式: C₂₆H₂₇NO₇
• 分子量: 465.503
• InChiKey: KFSYDKBHAJQIJL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  34
• 可旋转键数：
  12
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  106
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  allyl 4-(2-(allyloxy)-2-oxoethyl)-2-amino-6-(3,5-dimethoxyphenyl)-4H-chromene-3-carboxylate 在 间氯过氧苯甲酸 作用下， 以 二氯甲烷 为溶剂， 反应 25.0h， 以48%的产率得到oxiran-2-ylmethyl 2-amino-6-(3,5-dimethoxyphenyl)-4-(2-(oxiran-2-ylmethoxy)-2-oxoethyl)-4H-chromene-3-carboxylate
  参考文献：
  名称：

  Structure–Activity Relationship (SAR) Study of Ethyl 2-Amino-6-(3,5-dimethoxyphenyl)-4-(2-ethoxy-2-oxoethyl)-4H-chromene-3-carboxylate (CXL017) and the Potential of the Lead against Multidrug Resistance in Cancer Treatment

  摘要：

  Multidrug resistance (MDR) against standard therapies poses a serious challenge in cancer treatment, and there is a clinical need for new anticancer agents that would selectively target MDR malignancies. Our previous studies have identified a 4H-chromene system, CXL017 (4) as an example, that can preferentially kill MDR cancer cells. To further improve its potency, we have performed detailed structure-activity relationship (SAR) studies at the 3, 4, and 6 positions of the 4H-chromene system. The results reveal that the 3 and 4 positions prefer rigid and hydrophobic functional groups while the 6 position prefers a meta or para-substituted aryl functional group and the substituent should be small and hydrophilic. We have also identified and characterized nine MDR cancer cells that acquire MDR through different mechanisms and demonstrated the scope of our new lead, 9g, to selectively target different MDR cancers, which holds promise to help manage MDR in cancer treatment.

  DOI：

  10.1021/jm300515q
• 作为产物：
  描述：

  3,5-二甲氧基苯硼酸 在 palladium diacetate 、 sodium 、 potassium carbonate 、 三苯基膦 、 三氯氧磷 作用下， 以 乙二醇二甲醚 、 二氯甲烷 、 水 为溶剂， 反应 31.0h， 生成 allyl 4-(2-(allyloxy)-2-oxoethyl)-2-amino-6-(3,5-dimethoxyphenyl)-4H-chromene-3-carboxylate
  参考文献：
  名称：

  Structure–Activity Relationship (SAR) Study of Ethyl 2-Amino-6-(3,5-dimethoxyphenyl)-4-(2-ethoxy-2-oxoethyl)-4H-chromene-3-carboxylate (CXL017) and the Potential of the Lead against Multidrug Resistance in Cancer Treatment

  摘要：

  Multidrug resistance (MDR) against standard therapies poses a serious challenge in cancer treatment, and there is a clinical need for new anticancer agents that would selectively target MDR malignancies. Our previous studies have identified a 4H-chromene system, CXL017 (4) as an example, that can preferentially kill MDR cancer cells. To further improve its potency, we have performed detailed structure-activity relationship (SAR) studies at the 3, 4, and 6 positions of the 4H-chromene system. The results reveal that the 3 and 4 positions prefer rigid and hydrophobic functional groups while the 6 position prefers a meta or para-substituted aryl functional group and the substituent should be small and hydrophilic. We have also identified and characterized nine MDR cancer cells that acquire MDR through different mechanisms and demonstrated the scope of our new lead, 9g, to selectively target different MDR cancers, which holds promise to help manage MDR in cancer treatment.

  DOI：

  10.1021/jm300515q

文献信息

• Structure–Activity Relationship and Molecular Mechanisms of Ethyl 2-Amino-6-(3,5-dimethoxyphenyl)-4-(2-ethoxy-2-oxoethyl)-4<i>H</i>-chromene-3-carboxylate (CXL017) and Its Analogues
  作者：Sonia G. Das、Balasubramanian Srinivasan、David L. Hermanson、Nicholas P. Bleeker、Jignesh M. Doshi、Ruoping Tang、William T. Beck、Chengguo Xing

  DOI：10.1021/jm200764t

  日期：2011.8.25

  cytotoxicity in the NCI-60 panel of cell lines with an average IC50 of 1.04 μM. In addition, 5 has a unique mechanism of action in comparison with standard agents in the NCI database based on COMPARE analysis. Further structure–activity relationship study led to the development of a more potent analogue, compound 7d, with an IC50 of 640 nM in HL60/MX2. Additionally, one enantiomer of 5 is 13-fold more active

  癌症中的多药耐药 (MDR) 是一种现象，其中施用单一化学治疗剂会导致癌细胞对多种治疗产生交叉耐药性，即使具有不同的作用机制。针对标准疗法开发耐多药是癌症治疗的主要挑战。此前，我们已经证明了 CXL017 ( 5 ) 在 HL60/MX2 MDR 细胞中选择性靶向 MDR 癌细胞并与米托蒽醌 (MX) 协同作用的独特能力。在这里，我们扩大了其范围，并证明5可以在三种不同的 MDR 细胞系（HL60/DNR、K562/HHT300 和 CCRF-CEM/VLB100）中与长春新碱和紫杉醇产生协同作用。我们还证明了5在 NCI-60 细胞系组中具有强大的细胞毒性，平均 IC50个 1.04 μM。此外，与基于 COMPARE 分析的 NCI 数据库中的标准药物相比， 5具有独特的作用机制。进一步的构效关系研究导致开发了更有效的类似物化合物7d，在 HL60/MX2 中的 IC 50为 640
• Structure–Activity Relationship (SAR) Study of Ethyl 2-Amino-6-(3,5-dimethoxyphenyl)-4-(2-ethoxy-2-oxoethyl)-4<i>H</i>-chromene-3-carboxylate (CXL017) and the Potential of the Lead against Multidrug Resistance in Cancer Treatment
  作者：Gopalakrishnan Aridoss、Bo Zhou、David L. Hermanson、Nicholas P. Bleeker、Chengguo Xing

  DOI：10.1021/jm300515q

  日期：2012.6.14

  Multidrug resistance (MDR) against standard therapies poses a serious challenge in cancer treatment, and there is a clinical need for new anticancer agents that would selectively target MDR malignancies. Our previous studies have identified a 4H-chromene system, CXL017 (4) as an example, that can preferentially kill MDR cancer cells. To further improve its potency, we have performed detailed structure-activity relationship (SAR) studies at the 3, 4, and 6 positions of the 4H-chromene system. The results reveal that the 3 and 4 positions prefer rigid and hydrophobic functional groups while the 6 position prefers a meta or para-substituted aryl functional group and the substituent should be small and hydrophilic. We have also identified and characterized nine MDR cancer cells that acquire MDR through different mechanisms and demonstrated the scope of our new lead, 9g, to selectively target different MDR cancers, which holds promise to help manage MDR in cancer treatment.