methyl 3β-(chloroacetyloxy)-11-oxo-olean-12-en-30-oate | 1261081-68-8

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: methyl 3β-(chloroacetyloxy)-11-oxo-olean-12-en-30-oate
• 英文别名: methyl (2S,4aS,6aR,6aS,6bR,8aR,10S,12aS,14bR)-10-(2-chloroacetyl)oxy-2,4a,6a,6b,9,9,12a-heptamethyl-13-oxo-3,4,5,6,6a,7,8,8a,10,11,12,14b-dodecahydro-1H-picene-2-carboxylate
• CAS: 1261081-68-8
• 化学式: C₃₃H₄₉ClO₅
• 分子量: 561.202
• InChiKey: YEQSNXWJRBVKPG-UNXQSWAQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.9
• 重原子数：
  39
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.85
• 拓扑面积：
  69.7
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl 3β-(chloroacetyloxy)-11-oxo-olean-12-en-30-oate 在 四氯化钛 、 caesium carbonate 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 0.5h， 生成 3-(1-(2-((11-oxo-18β-olean-12-ene-30-carboxylic acid methyl ester)-3β-oxy)-2-oxoethyl)-1H-benzimidazol-2-yl)propionic acid
  参考文献：
  名称：

  18β-甘草次酸衍生物及其应用

  摘要：

  本发明属于医药技术领域，具体涉及具有Pin1抑制活性的18β‑甘草次酸衍生物及其药学上可接受的盐，该类衍生物的制备方法，以该衍生物为活性成分的药物组合物，以及在制备Pin1抑制剂，用于制备治疗和/或预防各种癌症的药物中的用途。本发明涉及的通式Ⅰ所示的衍生物或其药学上可接受的盐结构如下，R、X、Y、n如权利要求书和说明书所述。

  公开号：

  CN107118249B
• 作为产物：
  描述：

  甘草次酸 在 硫酸 作用下， 以 二氯甲烷 为溶剂， 反应 5.0h， 生成 methyl 3β-(chloroacetyloxy)-11-oxo-olean-12-en-30-oate
  参考文献：
  名称：

  Conjugates of 18β-glycyrrhetinic acid derivatives with 3-(1H-benzo[d]imidazol-2-yl)propanoic acid as Pin1 inhibitors displaying anti-prostate cancer ability

  摘要：

  Twenty-six conjugates of 18 beta-glycyrrhetinic acid derivatives with 3-(1H-benzo[d]imidazol-2-yl)propanoic acid were designed and synthesized as Pin1 inhibitors. Most of these semi-synthetic compounds showed improved Pin1 inhibitory activity and anti-proliferative effects against prostate cancer cells as compared to 3-(1H-benzo[d] imidazol-2-yl) propanoic acid and GA. Compounds 10a and 12i were the most potent to inhibit growth of prostate cancer PC-3 with GI(50) values of 7.80 mu M and 3.52 mu M, respectively. The enzyme inhibition ratio of nine compounds at 10 mu M was over 90%. Structure-activity relationships indicated that both appropriate structure at ring C of GA and suitable length of linker between GA skeleton and benzimidazole moiety had significant impact on improving activity. Western blot assay revealed that 10a decreased the level of cell cycle regulating protein cyclin D1. Thus, these compounds might represent a novel anti-proliferative agent working through Pin1 inhibition. (C) 2017 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2017.08.002

文献信息

• Synthesis and biological activity of some antitumor active derivatives from glycyrrhetinic acid
  作者：René Csuk、Stefan Schwarz、Ralph Kluge、Dieter Ströhl

  DOI：10.1016/j.ejmech.2010.09.028

  日期：2010.12

  Aminoalkyl substituted derivatives were synthesized starting from glycyrrhetinic acid methyl ester and screened for antitumor activity in a panel of 15 human cancer cell lines by an SRB assay. The most compound 7 possesses an aminohexyl side chain, induces apoptosis and shows IC50 values of 0.6–3.0 μM.

  从甘草次酸甲酯开始合成氨基烷基取代的衍生物，并通过SRB分析在15种人类癌细胞系中筛选抗肿瘤活性。最多的化合物7具有氨基己基侧链，诱导凋亡，IC 50值为0.6–3.0μM。
• Conjugates of 18β-glycyrrhetinic acid derivatives with 3-(1H-benzo[d]imidazol-2-yl)propanoic acid as Pin1 inhibitors displaying anti-prostate cancer ability
  作者：Kun Li、Tianyi Ma、Jingjing Cai、Min Huang、Hongye Guo、Di Zhou、Shenglin Luan、Jinyu Yang、Dan Liu、Yongkui Jing、Linxiang Zhao

  DOI：10.1016/j.bmc.2017.08.002

  日期：2017.10

  Twenty-six conjugates of 18 beta-glycyrrhetinic acid derivatives with 3-(1H-benzo[d]imidazol-2-yl)propanoic acid were designed and synthesized as Pin1 inhibitors. Most of these semi-synthetic compounds showed improved Pin1 inhibitory activity and anti-proliferative effects against prostate cancer cells as compared to 3-(1H-benzo[d] imidazol-2-yl) propanoic acid and GA. Compounds 10a and 12i were the most potent to inhibit growth of prostate cancer PC-3 with GI(50) values of 7.80 mu M and 3.52 mu M, respectively. The enzyme inhibition ratio of nine compounds at 10 mu M was over 90%. Structure-activity relationships indicated that both appropriate structure at ring C of GA and suitable length of linker between GA skeleton and benzimidazole moiety had significant impact on improving activity. Western blot assay revealed that 10a decreased the level of cell cycle regulating protein cyclin D1. Thus, these compounds might represent a novel anti-proliferative agent working through Pin1 inhibition. (C) 2017 Published by Elsevier Ltd.
• 18β-甘草次酸衍生物及其应用
  申请人：沈阳药科大学

  公开号：CN107118249B

  公开（公告）日：2019-12-20

  本发明属于医药技术领域，具体涉及具有Pin1抑制活性的18β‑甘草次酸衍生物及其药学上可接受的盐，该类衍生物的制备方法，以该衍生物为活性成分的药物组合物，以及在制备Pin1抑制剂，用于制备治疗和/或预防各种癌症的药物中的用途。本发明涉及的通式Ⅰ所示的衍生物或其药学上可接受的盐结构如下，R、X、Y、n如权利要求书和说明书所述。