4-O-[4-[formyl-[12-[formyl-[5-(4-methoxy-4-oxobutanoyl)oxy-3-(4-methoxy-4-oxobutanoyl)sulfanylpent-2-en-2-yl]amino]dodecyl]amino]-3-(4-methoxy-4-oxobutanoyl)sulfanylpent-3-enyl] 1-O-methyl butanedioate | 1236971-82-6

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: 4-O-[4-[formyl-[12-[formyl-[5-(4-methoxy-4-oxobutanoyl)oxy-3-(4-methoxy-4-oxobutanoyl)sulfanylpent-2-en-2-yl]amino]dodecyl]amino]-3-(4-methoxy-4-oxobutanoyl)sulfanylpent-3-enyl] 1-O-methyl butanedioate
• CAS: 1236971-82-6
• 化学式: C₄₄H₆₈N₂O₁₆S₂
• 分子量: 945.16
• InChiKey: QQMIWPZQRWCUPR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.47
• 重原子数：
  64.0
• 可旋转键数：
  37.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  232.56
• 氢给体数：
  0.0
• 氢受体数：
  18.0

反应信息

• 作为产物：
  描述：

  3,3'-dodecane-1,12-diylbis[5-(2-hydroxyethyl)-4-methyl-1,3-thiazol-3-ium] dibromide 、 丁二酸单甲酯酰氯 在 sodium hydroxide 、 三乙胺 作用下， 以 水 、 二氯甲烷 为溶剂， 反应 0.5h， 以74%的产率得到4-O-[4-[formyl-[12-[formyl-[5-(4-methoxy-4-oxobutanoyl)oxy-3-(4-methoxy-4-oxobutanoyl)sulfanylpent-2-en-2-yl]amino]dodecyl]amino]-3-(4-methoxy-4-oxobutanoyl)sulfanylpent-3-enyl] 1-O-methyl butanedioate
  参考文献：
  名称：

  Exploration of potential prodrug approach of the bis-thiazolium salts T3 and T4 for orally delivered antimalarials

  摘要：

  We report here the synthesis and biological evaluation of a series of 37 compounds as precursors of potent antimalarial bis-thiazolium salts ( T3 and T4). These prodrugs were either thioester, thiocarbonate or thiocarbamate type and were synthesized in one step by reaction of an alkaline solution of the parent drug with the appropriate activated acyl group. Structural variations affecting physicochemical properties were made in order to improve oral activity. Twenty-five of them exhibited potent antimalarial activity with IC50 lower than 7 nM against Plasmodium falciparum in vitro. Notably, 3 and 22 showed IC50 = 2.2 and 1.8 nM, respectively. After oral administration 22 was the most potent compound clearing the parasitemia in Plasmodium vinckei infected mice with a dose of 1.3 mg/kg. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.05.001