(3S,8R,10R,12R,14R,17S)-17-((S)-2-hydroxy-5-(isopropylamino)pentan-2-yl)-4,4,8,10,14-pentamethylhexadecahydro-1H-cyclopenta[a]phenanthrene-3,12-diol | 1444554-38-4

• 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: (3S,8R,10R,12R,14R,17S)-17-((S)-2-hydroxy-5-(isopropylamino)pentan-2-yl)-4,4,8,10,14-pentamethylhexadecahydro-1H-cyclopenta[a]phenanthrene-3,12-diol
• 英文别名: (3S,5R,8R,9R,10R,12R,13R,14R,17S)-17-[(2S)-2-hydroxy-5-(propan-2-ylamino)pentan-2-yl]-4,4,8,10,14-pentamethyl-2,3,5,6,7,9,11,12,13,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthrene-3,12-diol
• CAS: 1444554-38-4
• 化学式: C₃₀H₅₅NO₃
• 分子量: 477.772
• InChiKey: BOXXTLYFEZPPGD-HKUCOEKDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  34
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  72.7
• 氢给体数：
  4
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  原人参二醇 在 三乙酰氧基硼氢化钠 、 臭氧 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 0.08h， 生成 (3S,8R,10R,12R,14R,17S)-17-((S)-2-hydroxy-5-(isopropylamino)pentan-2-yl)-4,4,8,10,14-pentamethylhexadecahydro-1H-cyclopenta[a]phenanthrene-3,12-diol
  参考文献：
  名称：

  Discovery, synthesis, and structure–activity relationships of 20(S)-protopanaxadiol (PPD) derivatives as a novel class of AMPKα2β1γ1 activators

  摘要：

  Adenosine 5'-monophosphate-activated protein kinase (AMPK) has been demonstrated as a promising drug target due to its regulatory function in glucose and lipid metabolism. 20(S)-protopanoxadiol (PPD) was firstly identified from high throughput screening as a small molecule activator of AMPK subtype alpha 2 beta 1 gamma 1. In order to enhance its potency on AMPK, a series of PPD derivatives were synthesized and evaluated. Structure activity relationship study showed that the amine derivatives at the 24-position (groups 1 VI) can improve the potency (EC50: 0.7-2.3 mu M) and efficacy (fold: 2.5-3.8). Among them, compounds 12 and 13 exhibited the best potency (EC50: 12 and 0.7 mu M) and efficacy (fold: 3.7 and 3.8). Further study suggested the mechanism of AMPK activation may functioned at the allosteric position, resulting the inhibition of the lipid synthesis in HepG2 cell model. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.04.010

文献信息

• 20(S)-Protopanaxadiol (PPD) analogues chemosensitize multidrug-resistant cancer cells to clinical anticancer drugs
  作者：Junhua Liu、Xu Wang、Peng Liu、Rongxin Deng、Min Lei、Wantao Chen、Lihong Hu

  DOI：10.1016/j.bmc.2013.04.067

  日期：2013.7

  analogues were designed, synthesized, and evaluated for the chemosensitizing activity against a multidrug resistant (MDR) cell line (KBvcr) overexpressing P-glycoprotein (P-gp). Structure–activity relationship analysis showed that aromatic substituted aliphatic amine at the 24-positions (groups V) effectively and significantly sensitized P-gp overexpressing multidrug resistant (MDR) cells to anticancer

  设计，合成和评估了新型20（S）-原戊二醇（PPD）类似物，并针对过表达P-糖蛋白（P-gp）的耐多药（MDR）细胞系（KBvcr）进行了化学增敏活性。结构-活性关系分析表明，芳族取代的脂肪族胺在24位（V组）有效且显着地使过表达P-gp的多药耐药（MDR）细胞对多西他赛（DOC），长春新碱（VCR）等抗癌药物敏感，和阿霉素（ADM）。PPD衍生品12和18对DOC和VCR的有效逆转能力比维拉帕米（VER）高1.3-2.6倍。重要的是，活性PPD类似物（5μM）对非MDR和MDR细胞均未观察到细胞毒性，这表明PPD类似物可作为一种有效的，安全的抗性调节剂的新型先导化合物。此外，初步的机制研究表明，PPD类似物的化学增敏活性是由抑制在MDR癌细胞中过度表达的P-糖蛋白（P-gp）引起的。
• Discovery, synthesis, and structure–activity relationships of 20(S)-protopanaxadiol (PPD) derivatives as a novel class of AMPKα2β1γ1 activators
  作者：Junhua Liu、Dakai Chen、Peng Liu、Mengna He、Jia Li、Jingya Li、Lihong Hu

  DOI：10.1016/j.ejmech.2014.04.010

  日期：2014.5

  Adenosine 5'-monophosphate-activated protein kinase (AMPK) has been demonstrated as a promising drug target due to its regulatory function in glucose and lipid metabolism. 20(S)-protopanoxadiol (PPD) was firstly identified from high throughput screening as a small molecule activator of AMPK subtype alpha 2 beta 1 gamma 1. In order to enhance its potency on AMPK, a series of PPD derivatives were synthesized and evaluated. Structure activity relationship study showed that the amine derivatives at the 24-position (groups 1 VI) can improve the potency (EC50: 0.7-2.3 mu M) and efficacy (fold: 2.5-3.8). Among them, compounds 12 and 13 exhibited the best potency (EC50: 12 and 0.7 mu M) and efficacy (fold: 3.7 and 3.8). Further study suggested the mechanism of AMPK activation may functioned at the allosteric position, resulting the inhibition of the lipid synthesis in HepG2 cell model. (C) 2014 Elsevier Masson SAS. All rights reserved.