3-chloro-4-methyl-7-<(E)-3-(2,3,4,5-tetrahydro-4-methylidene-5-oxofuran-2-yl)but-2-enyloxy>-2H-1-benzopyran-2-one

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 英文名称: 3-chloro-4-methyl-7-<(E)-3-(2,3,4,5-tetrahydro-4-methylidene-5-oxofuran-2-yl)but-2-enyloxy>-2H-1-benzopyran-2-one
• 英文别名: 3-chloro-4-methyl-7-[(E)-3-(4-methylidene-5-oxooxolan-2-yl)but-2-enoxy]chromen-2-one
• 化学式: C₁₉H₁₇ClO₅
• 分子量: 360.794
• InChiKey: FECVXZMABMIJCL-UXBLZVDNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  61.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  3-氯-7-羟基-4-甲基香豆素 在 selenium(IV) oxide 、 铜 、 potassium carbonate 、 对苯二酚 、 potassium iodide 、 锌 作用下， 以 四氢呋喃 、 乙醇 、 丙酮 为溶剂， 反应 65.0h， 生成 3-chloro-4-methyl-7-<(E)-3-(2,3,4,5-tetrahydro-4-methylidene-5-oxofuran-2-yl)but-2-enyloxy>-2H-1-benzopyran-2-one
  参考文献：
  名称：

  Geiparvarin Analogues: Synthesis and Anticancer Evaluation ofα-Methylidene-γ-butyrolactone-Bearing Coumarins

  摘要：

  To determine some of the structural features of geiparvarin that account for its cytostatic activity in vitro, certain geiparvarin analogues modified in the furan-3(2H)-one moiety and the alkenyloxy substituent were synthesized and tested against the growth of 60 human cancer cell lines derived from nine cancer-cell types. These compounds demonstrated a strong growth-inhibitory activity against leukemia cell lines but were relatively inactive against non-small-cell lung cancers and CNS cancers. Comparison of the mean log GI, values of gamma-[(E)-1-methylprop-1-enyl]-alpha-methylidene-gamma-butyrolactones 7-9 revealed that 7-[(E)-3-(2,3,4,5-tetrahydro-4-methylidene-5-oxofuran-2-yl)but-2-enyloxy]-2H-1-benzopyran-2-one (8: - 5.47) was more active than its 6-substituted counterpart 7 (- 5.21) and its 3-chloro-4-methyl derivative 9 (- 5.31) and had a potency similar to that of geiparvarin (log GI(50) = - 5.41). These results indicated that the furan-3(2H)-one moiety of geiparvarin could be replaced by an alpha-methylidene-gamma-butyrolactone unit without losing the anticancer potency, (:nd that the best substitution site at the coumarin moiety was C(7). The alkenyloxy substituent of 8 was also replaced by a methoxy substituent. Among these alpha-methylidene-gamma-butyrolactones, 7-[(2,3,4,5-tetrahydro-4-methylidene-5-oxo-2-phenyliuran-2-yl)methoxy]-2H-1-benzopyran-2-one (1l) was the most potent with a mean log GI(50) value of - 5.83 and a range value of 132(10(212)).

  DOI：

  10.1002/(sici)1522-2675(19990210)82:2<191::aid-hlca191>3.0.co;2-p

文献信息

• Geiparvarin Analogues: Synthesis and Anticancer Evaluation ofα-Methylidene-γ-butyrolactone-Bearing Coumarins
  作者：Yeh-Long Chen、Tai-Chi Wang、Cherng-Chyi Tzeng、Nein-Chen Chang

  DOI：10.1002/(sici)1522-2675(19990210)82:2<191::aid-hlca191>3.0.co;2-p

  日期：1999.2.10

  To determine some of the structural features of geiparvarin that account for its cytostatic activity in vitro, certain geiparvarin analogues modified in the furan-3(2H)-one moiety and the alkenyloxy substituent were synthesized and tested against the growth of 60 human cancer cell lines derived from nine cancer-cell types. These compounds demonstrated a strong growth-inhibitory activity against leukemia cell lines but were relatively inactive against non-small-cell lung cancers and CNS cancers. Comparison of the mean log GI, values of gamma-[(E)-1-methylprop-1-enyl]-alpha-methylidene-gamma-butyrolactones 7-9 revealed that 7-[(E)-3-(2,3,4,5-tetrahydro-4-methylidene-5-oxofuran-2-yl)but-2-enyloxy]-2H-1-benzopyran-2-one (8: - 5.47) was more active than its 6-substituted counterpart 7 (- 5.21) and its 3-chloro-4-methyl derivative 9 (- 5.31) and had a potency similar to that of geiparvarin (log GI(50) = - 5.41). These results indicated that the furan-3(2H)-one moiety of geiparvarin could be replaced by an alpha-methylidene-gamma-butyrolactone unit without losing the anticancer potency, (:nd that the best substitution site at the coumarin moiety was C(7). The alkenyloxy substituent of 8 was also replaced by a methoxy substituent. Among these alpha-methylidene-gamma-butyrolactones, 7-[(2,3,4,5-tetrahydro-4-methylidene-5-oxo-2-phenyliuran-2-yl)methoxy]-2H-1-benzopyran-2-one (1l) was the most potent with a mean log GI(50) value of - 5.83 and a range value of 132(10(212)).