| 300542-85-2

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• CAS: 300542-85-2
• 化学式: C₅₆H₈₆N₂O₁₄
• 分子量: 1011.3
• InChiKey: HBVUCHMMQPBKJZ-UUOUGWEJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.58
• 重原子数：
  72.0
• 可旋转键数：
  12.0
• 环数：
  9.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  228.3
• 氢给体数：
  2.0
• 氢受体数：
  14.0

反应信息

• 作为反应物：
  描述：

  在 iron(II) chloride 作用下， 以 乙腈 为溶剂， 反应 5.0h， 以97%的产率得到3-oxo-7α,12α-diacetoxy-5β-cholan-24-amide
  参考文献：
  名称：

  Tetraoxane Antimalarials and Their Reaction with Fe(II)

  摘要：

  Mixed tetraoxanes 5a and 13 synthesized from cholic acid and 4-oxocyclohexanecarboxylic acid were as active as artemisinin against chloroquine-susceptible, chloroquine-resistant, and multidrug-resistant Plasmodium falciparum strains (IC50, IC90). Most active 13 is metabolically stable in in vitro metabolism studies. In vivo studies on tetraoxanes with a C(4'') methyl group afforded compound 15, which cured 4/5 mice at 600 and 200 mg, kg(-1), day(-1), and 2/5 mice at 50 mg, kg(-1), day(-1), showing no toxic effects. Tetraoxane 19 was an extremely active antiproliferative with LC50 of 17 nM and maximum tolerated dose of 400 mg/kg. In Fe(II)-induced scission of tetraoxane antimalarials only RO center dot radicals were detected by EPR experiments. This finding and the indication of Fe(IV)=O species led us to propose that RO center dot radicals are probably capable of inducing the parasite's death. Our results suggest that C radicals are possibly not the only lethal species derived from peroxide prodrug antimalarials, as currently believed.

  DOI：

  10.1021/jm050966r
• 作为产物：
  描述：

  (5beta,7alpha,12alpha)-7,12-双(乙酰氧基)-3-酮基胆烷-24-酸 在 氯化亚砜 、 双(三甲基硅基)过氧化物 、 三氟甲磺酸三甲基硅酯 、 氯化铵 、 三乙胺 作用下， 以 二氯甲烷 、 乙腈 、 苯 为溶剂， 反应 3.0h， 生成
  参考文献：
  名称：

  Cholic Acid Derivatives as 1,2,4,5-Tetraoxane Carriers:  Structure and Antimalarial and Antiproliferative Activity

  摘要：

  Cholic acid-derived 1,2,4,5-tetraoxanes were synthesized in order to explore the influence of steroid carrier on its antimalarial and antiproliferative activity in vitro. Starting with chiral ketones, cis and trans series of diastereomeric tetraoxanes were obtained, and the cis series was found to be similar to 2 times as active as the trans against Plasmodium falciparum DG and W2 clones. The same tendency was observed against human melanoma (Fem-X) and human cervix carcinoma (HeLa) cell lines. The amide C(24) termini, for the first time introduced into the carrier molecule of a tetraoxane pharmacophore, significantly enhanced both antimalarial and antiproliferative activity, as compared to the corresponding methyl esters, with cis-bis(N-propylamide) being most efficient against the chloroquine-susceptible D6 clone (IC50 = 9.29 nM). cis- and trans-bis(N-propylamides) were also screened against PBMC, and PRA-stimulated PBMC, showing a cytotoxicity/antimalarial potency ratio of 1/10 000.

  DOI：

  10.1021/jm000952f