methyl (7E)-7-[(2R)-2-[(E)-oct-1-enyl]-5-oxocyclopent-3-en-1-ylidene]heptanoate | 98461-80-4

• 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: methyl (7E)-7-[(2R)-2-[(E)-oct-1-enyl]-5-oxocyclopent-3-en-1-ylidene]heptanoate
• CAS: 98461-80-4
• 化学式: C₂₁H₃₂O₃
• 分子量: 332.483
• InChiKey: ZCZKCNMVKKKMNI-MPZMTSDYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  24
• 可旋转键数：
  13
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  43.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl (7E)-7-[(2R)-2-[(E)-oct-1-enyl]-5-oxocyclopent-3-en-1-ylidene]heptanoate 在 porcine liver esterase 、 硫酸氢铵 、 phosphate buffer 作用下， 反应 4.0h， 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
• 作为产物：
  描述：

  反式-1-碘-1-辛烯 在 4-二甲氨基吡啶 、 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 31.0h， 生成 methyl (7E)-7-[(2R)-2-[(E)-oct-1-enyl]-5-oxocyclopent-3-en-1-ylidene]heptanoate
  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

• 5-Alkylidene-2-halo-4-substituted-2-cyclopentenone and process for production thereof
  申请人：TEIJIN LIMITED

  公开号：EP0131441A2

  公开（公告）日：1985-01-16

  Novel 5-alkylidene-2-halo-4-substituted-2- cyclopentenone and process for production thereof. The novel 5-alkylidene-2-halo-4-substituted-2-cyclopentenones are represented by the following formula (I): wherein Ra represents a substituted or unsubstituted aliphatic hydrocarbon group having 1 to 12 carbon atoms or a substituted or unsubstituted phenyl group, Rb represents a substituted or unsubstituted aliphatic hydrocarbon group having 1 to 12 carbon atoms, and X represents a halogen atom. The novel cyclopentenones possess excellent pharmaceutical activities including anti-tumor activity, antiviral activity and antimicrobial activity.

  新型 5-亚烷基-2-卤代-4-取代-2-环戊烯酮及其生产工艺。 新型 5-亚烷基-2-卤代-4-取代-2-环戊烯酮由下式（I）表示：其中 Ra 代表具有 1 至 12 个碳原子的取代或未取代的脂肪族烃基或取代或未取代的苯基，Rb 代表具有 1 至 12 个碳原子的取代或未取代的脂肪族烃基，X 代表卤素原子。 新型环戊烯酮具有优异的药物活性，包括抗肿瘤活性、抗病毒活性和抗菌活性。
• US4689426A
  申请人：——

  公开号：US4689426A

  公开（公告）日：1987-08-25
• 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.