(7E)-7-[(2R)-2-[(E)-oct-1-enyl]-5-oxocyclopent-3-en-1-ylidene]heptanoic acid | 212069-95-9

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: (7E)-7-[(2R)-2-[(E)-oct-1-enyl]-5-oxocyclopent-3-en-1-ylidene]heptanoic acid
• CAS: 212069-95-9
• 化学式: C₂₀H₃₀O₃
• 分子量: 318.456
• InChiKey: UACBDPBIHHMYBA-DJIZZMMISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  23
• 可旋转键数：
  12
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  54.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  反式-1-碘-1-辛烯 在 porcine liver esterase 、 4-二甲氨基吡啶 、 硫酸氢铵 、 phosphate buffer 、 Dimethylzinc 、 叔丁基锂 、 溶剂黄146 、 甲基磺酰氯 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 35.0h， 生成 (7E)-7-[(2R)-2-[(E)-oct-1-enyl]-5-oxocyclopent-3-en-1-ylidene]heptanoic acid
  参考文献：
  名称：

  Rational Design of Antitumor Prostaglandins with High Biological Stability

  摘要：

  Molecular design can overcome the metabolic instability of Delta(7)-PGA(1), while maintaining its antitumor potency. Saturation of the C(13)-C(14) double bond enhances the biological stability but decreases the antiproliferative activity. Configurational inversion of the isomerase-sensitive C(12) stereocenter from the natural S to the unnatural R geometry not only enhances biological stability but also significantly suppresses the growth of the tumor cells. The 12R derivatives markedly increase the induction of p21, a Cdk inhibitor, leading to sharp cell cycle arrest at the G(1) phase at a dose level so low that at this dose Delta(7)-PGA(1) methyl ester scarcely exerts an effect. These conspicuous biological properties lead to long-term suppression of tumor cell growth. The structure-stability relationship demonstrates that the stability of prostaglandins (PGs) is crucially controlled by the C(12) configuration and is unaffected by the geometry of the hydroxy-bearing C(15). The successful design of antitumor PGs resistant to enzymatic metabolism provides a new strategy applicable to creating a useful PG for cancer chemotherapy.

  DOI：

  10.1021/jm9801657

文献信息

• Rational Design of Antitumor Prostaglandins with High Biological Stability
  作者：Masaaki Suzuki、Toshihiro Kiho、Keiichiro Tomokiyo、Kyoji Furuta、Shoji Fukushima、Yoshikazu Takeuchi、Makoto Nakanishi、Ryoji Noyori

  DOI：10.1021/jm9801657

  日期：1998.7.1

  Molecular design can overcome the metabolic instability of Delta(7)-PGA(1), while maintaining its antitumor potency. Saturation of the C(13)-C(14) double bond enhances the biological stability but decreases the antiproliferative activity. Configurational inversion of the isomerase-sensitive C(12) stereocenter from the natural S to the unnatural R geometry not only enhances biological stability but also significantly suppresses the growth of the tumor cells. The 12R derivatives markedly increase the induction of p21, a Cdk inhibitor, leading to sharp cell cycle arrest at the G(1) phase at a dose level so low that at this dose Delta(7)-PGA(1) methyl ester scarcely exerts an effect. These conspicuous biological properties lead to long-term suppression of tumor cell growth. The structure-stability relationship demonstrates that the stability of prostaglandins (PGs) is crucially controlled by the C(12) configuration and is unaffected by the geometry of the hydroxy-bearing C(15). The successful design of antitumor PGs resistant to enzymatic metabolism provides a new strategy applicable to creating a useful PG for cancer chemotherapy.