1,12-bis-(N,N'-methylsulfonyloxyacetamidinyl)dodecane | 928837-44-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机磺酸及其衍生物
• 英文名称: 1,12-bis-(N,N'-methylsulfonyloxyacetamidinyl)dodecane
• 英文别名: 1,12-bis (N,N'-methylsulfonyloxyacetamidinyl) dodecane；[[C-methyl-N-[12-[1-(methylsulfonyloxyamino)ethylideneamino]dodecyl]carbonimidoyl]amino] methanesulfonate
• CAS: 928837-44-9
• 化学式: C₁₈H₃₈N₄O₆S₂
• 分子量: 470.655
• InChiKey: DJDYJOFOXDVRIH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  30
• 可旋转键数：
  19
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  152
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  1,12-二氨基十二烷 在 吡啶 作用下， 以 乙醇 、 氯仿 为溶剂， 反应 100.0h， 生成 1,12-bis-(N,N'-methylsulfonyloxyacetamidinyl)dodecane
  参考文献：
  名称：

  Compounds with antiparasitic activity and medicines containing same

  摘要：

  这项发明涉及具有抗寄生虫特别是抗疟活性的化合物，其特征在于它们符合一般式(I)。特别适用于具有抗寄生虫活性的化合物。

  公开号：

  US20050176819A1

文献信息

• Synthesis and antimalarial activity of new 1,12-bis(N,N′-acetamidinyl)dodecane derivatives
  作者：Mahama Ouattara、Sharon Wein、Michèle Calas、Yen Vo Hoang、Henri Vial、Roger Escale

  DOI：10.1016/j.bmcl.2006.11.013

  日期：2007.2

  Amidoxime and O-substituted derivatives of the bis-alkylamidine 1,12-bis(N,N'-acetamidinyl)dodecane were synthesized and evaluated as in vitro and in vivo antimalarial prodrugs. The bis-O-methylsulfonylamidoxime 8 and the bis-oxadiazolone 9 derivatives show relatively potent antimalarial activity after oral administration.

  合成了双烷基am 1,12-双（N，N'-乙酰胺基）十二烷的ox胺肟和O-取代衍生物，并作为体外和体内抗疟原药进行了评估。双-O-甲基磺酰胺基肟8和双-恶二唑酮9衍生物口服后显示出相对有效的抗疟活性。
• Evaluation of Bis-Alkylamidoxime<i>O</i>-Alkylsulfonates as Orally Available Antimalarials
  作者：Mélissa Degardin、Sharon Wein、Smitha Gouni、Christophe Tran Van Ba、Jean-Frédéric Duckert、Thierry Durand、Roger Escale、Henri Vial、Yen Vo-Hoang

  DOI：10.1002/cmdc.201200112

  日期：2012.6

  metabolism. Unfortunately, these compounds are not orally available. To solve this absorption issue, we investigated a prodrug strategy based on sulfonate derivatives of alkylamidoximes. A total of 25 sulfonates were synthesized as prodrug candidates of one bis‐N‐alkylamidine and of six N‐substituted bis‐C‐alkylamidines. Their antimalarial activities were evaluated in vitro against P. falciparum and in vivo

  控制疟疾的主要威胁是疟原虫新出现的多药耐药性 。寄生虫。双烷基am被开发为靶向血浆磷脂代谢的潜在新化学疗法。不幸的是，这些化合物不是口服可获得的。为了解决该吸收问题，我们研究了基于烷基氨基肟磺酸盐衍生物的前药策略。总共合成了25种磺酸盐作为一种双N- N-烷基am和六个N-取代的双C - C-烷基am的前药候选物。在体外针对恶性疟原虫和在体内针对温氏疟原虫评估了它们的抗疟活性。在小鼠中定义构效关系。C-烷基和N-烷基am的磺酸盐基团上的小烷基取代基具有最佳的口服抗疟活性；将烷基磺酸盐衍生物化学转化为相应的烷基am。
• Pharmacokinetic properties and metabolism of a new potent antimalarial N-alkylamidine compound, M64, and its corresponding bioprecursors
  作者：Delphine Margout、Florence Gattacceca、Georges Moarbess、Sharon Wein、Christophe Tran van Ba、Samuel Le Pape、Olivier Berger、Roger Escale、Henri J. Vial、Françoise M.M. Bressolle

  DOI：10.1016/j.ejps.2010.10.012

  日期：2011.1

  Antimalarial activities and pharmacokinetics of the bis-alkylamidine, M64, and its amidoxime, M64-AH, and O-methylsulfonate, M64-S-Me, derivatives were investigated. M64 and M64-S-Me had the most potent activity against the Plasmodium falciparum growth (IC50 <= 12 nM). The three compounds can clear the Plasmodium vinckei infection in mice (ED50 < 10 mg/kg). A liquid chromatography-mass spectrometry method was validated to simultaneously quantify M64 and M64-AH in human and rat plasma. M64 is partially metabolized to M64-monoamidoxime and M64-monoacetamide by rat and mouse liver microsomes. The amidoxime M64-AH undergoes extensive metabolism forming M64, M64-monoacetamide, M64-diacetamide and M64-monoamidoxime. Strong interspecies differences were observed. The pharmacokinetic profiles of M64. M64-AH and M64-S-Me were studied in rat after intravenous and oral administrations. M64 is partially metabolized to M64-AH; while M64-S-Me is rapidly and totally converted to M64 and M64-AH. M64-AH is mostly oxidized to the inactive M64-diacetamine while its N-reduction to the efficient M64 is a minor metabolic pathway. Oral dose of M64-AH was well absorbed (38%) and converted to M64 and M64-diacetamide. This study generated substantial information about the properties of this class of antimalarial drugs. Other routes of synthesis will be explored to prevent oxidative transformation of the amidoxime and to favour the N-reduction. (C) 2010 Elsevier B.V. All rights reserved.
• Compounds with antiparasitic activity and medicines containing same
  申请人：Vial Henri

  公开号：US20050176819A1

  公开（公告）日：2005-08-11

  The invention relates to compounds having an anti-parasitic, in particular antimalarial activity, characterized in that they correspond to general formula (I) Applications in particular as compounds with anti-parasitic activity.

  这项发明涉及具有抗寄生虫特别是抗疟活性的化合物，其特征在于它们符合一般式(I)。特别适用于具有抗寄生虫活性的化合物。