2-methoxy-2-((R)-3-(4-methoxybenzyl)-2-oxothiazolidin-4-yl)-tetrahydro-2H-pyran-4-yl 3-iodobenzoate

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-methoxy-2-((R)-3-(4-methoxybenzyl)-2-oxothiazolidin-4-yl)-tetrahydro-2H-pyran-4-yl 3-iodobenzoate
• 英文别名: [2-methoxy-2-[(4R)-3-[(4-methoxyphenyl)methyl]-2-oxo-1,3-thiazolidin-4-yl]oxan-4-yl] 3-iodobenzoate
• 化学式: C₂₄H₂₆INO₆S
• 分子量: 583.444
• InChiKey: ABSLHOFCQGQIGO-DQBMGFJSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  33
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  99.6
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  (R)-N-methoxy-3-(4-methoxybenzyl)-N-methyl-2-oxothiazolidine-4-carboxamide 在 盐酸 、 4-二甲氨基吡啶 、 Hoveyda-Grubbs catalyst second generation 、 水 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 1,2-二氯乙烷 为溶剂， 反应 36.0h， 生成 2-methoxy-2-((R)-3-(4-methoxybenzyl)-2-oxothiazolidin-4-yl)-tetrahydro-2H-pyran-4-yl 3-iodobenzoate
  参考文献：
  名称：

  Truncated Latrunculins as Actin Inhibitors Targeting Plasmodium falciparum Motility and Host Cell Invasion

  摘要：

  Polymerization of the cytosolic protein actin is critical to cell movement and host cell invasion by the malaria parasite, Plasmodium falciparum. Any disruption to actin polymerization dynamics will render the parasite incapable of invading a host cell and thereby unable to cause infection. Here, we explore the potential of using truncated latrunculins as potential chemotherapeutics for the treatment of malaria. Exploration of the binding interactions of the natural actin inhibitor latrunculins with actin revealed how a truncated core of the inhibitor could retain its key interaction features with actin. This truncated core was synthesized and subjected to preliminary structure activity relationship studies to generate a focused set of analogues. Biochemical analyses of these analogues demonstrate their 6-fold increased activity compared with that of latrunculin B against P. falciparum and a 16-fold improved selectivity ex vivo. These data establish the latrunculin core as a potential focus for future structure-based drug design of chemotherapeutics against malaria.

  DOI：

  10.1021/acs.jmedchem.6b01109

文献信息

• Truncated Latrunculins as Actin Inhibitors Targeting <i>Plasmodium falciparum</i> Motility and Host Cell Invasion
  作者：Swapna Johnson、Raphaël Rahmani、Damien R. Drew、Melanie J. Williams、Mark Wilkinson、Yan Hong Tan、Johnny X. Huang、Christopher J. Tonkin、James G. Beeson、Jake Baum、Brian J. Smith、Jonathan B. Baell

  DOI：10.1021/acs.jmedchem.6b01109

  日期：2016.12.22

  Polymerization of the cytosolic protein actin is critical to cell movement and host cell invasion by the malaria parasite, Plasmodium falciparum. Any disruption to actin polymerization dynamics will render the parasite incapable of invading a host cell and thereby unable to cause infection. Here, we explore the potential of using truncated latrunculins as potential chemotherapeutics for the treatment of malaria. Exploration of the binding interactions of the natural actin inhibitor latrunculins with actin revealed how a truncated core of the inhibitor could retain its key interaction features with actin. This truncated core was synthesized and subjected to preliminary structure activity relationship studies to generate a focused set of analogues. Biochemical analyses of these analogues demonstrate their 6-fold increased activity compared with that of latrunculin B against P. falciparum and a 16-fold improved selectivity ex vivo. These data establish the latrunculin core as a potential focus for future structure-based drug design of chemotherapeutics against malaria.