3-(1-(2-((18β-olean-9(11),12-diene-30-carboxylic acid methyl ester)-3β-oxy)-3-oxopropyl)-1H-benzimidazol-2-yl)propionic acid

• 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: 3-(1-(2-((18β-olean-9(11),12-diene-30-carboxylic acid methyl ester)-3β-oxy)-3-oxopropyl)-1H-benzimidazol-2-yl)propionic acid
• 英文别名: 3-(1-(3-((methyl 18β-olean-9(11),12-dien-30-oate)-3β-oxy)-3-oxopropyl)-1H-benzo[d]imidazol-2-yl)propanoic acid；3-[1-[3-[[(3S,4aR,6aS,6bR,8aS,11S,12aR,14bS)-11-methoxycarbonyl-4,4,6a,6b,8a,11,14b-heptamethyl-1,2,3,4a,5,6,7,8,9,10,12,12a-dodecahydropicen-3-yl]oxy]-3-oxopropyl]benzimidazol-2-yl]propanoic acid
• 化学式: C₄₄H₆₀N₂O₆
• 分子量: 712.97
• InChiKey: HCYFUZSHTZPJFH-NHTAEXKHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9
• 重原子数：
  52
• 可旋转键数：
  10
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  108
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  丙考达唑 在 5%-palladium/activated carbon 、 氢气 、 potassium carbonate 、 caesium carbonate 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 34.0h， 生成 3-(1-(2-((18β-olean-9(11),12-diene-30-carboxylic acid methyl ester)-3β-oxy)-3-oxopropyl)-1H-benzimidazol-2-yl)propionic acid
  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