3'R,4'R-di-(E)-phenylacryloyloxy-2',2'-dimethyl-2-ethyldihydropyrano[2,3f]chromone | 1257415-54-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: 3'R,4'R-di-(E)-phenylacryloyloxy-2',2'-dimethyl-2-ethyldihydropyrano[2,3f]chromone
• 英文别名: [(9R,10R)-2-ethyl-8,8-dimethyl-4-oxo-9-[(E)-3-phenylprop-2-enoyl]oxy-9,10-dihydropyrano[2,3-f]chromen-10-yl] (E)-3-phenylprop-2-enoate
• CAS: 1257415-54-5
• 化学式: C₃₄H₃₀O₇
• 分子量: 550.608
• InChiKey: CNJSEPJCRVZCGC-ZIXBCMQKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.6
• 重原子数：
  41
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  88.1
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  3-苯基-2-丙烯酰氯 、 3'R,4'R-dihydroxy-2',2'-dimethyl-2-ethylpyrano[2,3-f]chromone 在 4-二甲氨基吡啶 作用下， 以 二氯甲烷 为溶剂， 以65%的产率得到3'R,4'R-di-(E)-phenylacryloyloxy-2',2'-dimethyl-2-ethyldihydropyrano[2,3f]chromone
  参考文献：
  名称：

  Antitumor Agents 286. Design, Synthesis, and Structure−Activity Relationships of 3′R,4′R-Disubstituted-2′,2′-dimethyldihydropyrano[2,3-f]chromone (DSP) Analogues as Potent Chemosensitizers to Overcome Multidrug Resistance

  摘要：

  In this study, various 3'R,4'R-disubstituted-2',2'-dimethydihydropyrano[2,3-f]chromone (DSP) derivatives were discovered as potent chemosensitizers in the treatment of multidrug resistant cancer cells. Twenty-four DSP analogues (5-28) were synthesized and evaluated against a multidrug resistant (MDR) cell line (KB-Vin) with and without vincristine (VCR). All DSP analogues exhibited low intrinsic cytotoxicity. However, in combination treatment, most DSPs reversed resistance to VCR and lowered the GI(50) value of VCR by 12-349-fold. At a concentration of 1 mu g/mL, three compounds, 11, 14, and 21, fully reversed resistance to VCR in KB-Vin cancer cells, a 2-fold increase compared to verapamil, a first-generation chemosensitizer. Detailed structure-activity relationship (SAR) conclusions were established based on 3' and 4' substitutions. Moreover, a preliminary mechanism study indicated that the chemosensitizing activity of DSP analogues results from inhibition of P-glycoprotein (P-gp) overexpressed in MDR cancer cells.

  DOI：

  10.1021/jm101249z

文献信息

• Antitumor Agents 286. Design, Synthesis, and Structure−Activity Relationships of 3′<i>R</i>,4′<i>R</i>-Disubstituted-2′,2′-dimethyldihydropyrano[2,3-<i>f</i>]chromone (DSP) Analogues as Potent Chemosensitizers to Overcome Multidrug Resistance
  作者：Ting Zhou、Qian Shi、Kenneth F. Bastow、Kuo-Hsiung Lee

  DOI：10.1021/jm101249z

  日期：2010.12.23

  In this study, various 3'R,4'R-disubstituted-2',2'-dimethydihydropyrano[2,3-f]chromone (DSP) derivatives were discovered as potent chemosensitizers in the treatment of multidrug resistant cancer cells. Twenty-four DSP analogues (5-28) were synthesized and evaluated against a multidrug resistant (MDR) cell line (KB-Vin) with and without vincristine (VCR). All DSP analogues exhibited low intrinsic cytotoxicity. However, in combination treatment, most DSPs reversed resistance to VCR and lowered the GI(50) value of VCR by 12-349-fold. At a concentration of 1 mu g/mL, three compounds, 11, 14, and 21, fully reversed resistance to VCR in KB-Vin cancer cells, a 2-fold increase compared to verapamil, a first-generation chemosensitizer. Detailed structure-activity relationship (SAR) conclusions were established based on 3' and 4' substitutions. Moreover, a preliminary mechanism study indicated that the chemosensitizing activity of DSP analogues results from inhibition of P-glycoprotein (P-gp) overexpressed in MDR cancer cells.