(3S,8R,10R,12R,14R,17S)-4,4,8,10,14-pentamethyl-17-((R)-2-methyl-5-oxotetrahydrofuran-2-yl)hexadecahydro-1H-cyclopenta[a]phenanthrene-3,12-diyl diacetate | 1609408-04-9

• 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)-4,4,8,10,14-pentamethyl-17-((R)-2-methyl-5-oxotetrahydrofuran-2-yl)hexadecahydro-1H-cyclopenta[a]phenanthrene-3,12-diyl diacetate
• CAS: 1609408-04-9
• 化学式: C₃₁H₄₈O₆
• 分子量: 516.719
• InChiKey: FALKTBWNZWZGNQ-HGCDOECSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.24
• 重原子数：
  37.0
• 可旋转键数：
  3.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  78.9
• 氢给体数：
  0.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  (3S,8R,10R,12R,14R,17S)-4,4,8,10,14-pentamethyl-17-((R)-2-methyl-5-oxotetrahydrofuran-2-yl)hexadecahydro-1H-cyclopenta[a]phenanthrene-3,12-diyl diacetate 在 sodium hydroxide 作用下， 以 四氢呋喃 为溶剂， 反应 7.0h， 生成 (4S)-4-((3S,8R,10R,12R,14R,17S)-3,12-dihydroxy-4,4,8,10,14-pentamethylhexadecahydro-1H-cyclopenta[a]phenanthren-17-yl)-4-hydroxy-N-isobutylpentanamide
  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
• 作为产物：
  描述：

  原人参二醇 在 吡啶 、 potassium permanganate 、 sodium periodate 作用下， 以 水 、 丙酮 为溶剂， 反应 26.0h， 生成 (3S,8R,10R,12R,14R,17S)-4,4,8,10,14-pentamethyl-17-((R)-2-methyl-5-oxotetrahydrofuran-2-yl)hexadecahydro-1H-cyclopenta[a]phenanthrene-3,12-diyl diacetate
  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