methyl 4-(4,4-dihydroperoxycyclohexyl)benzoate | 1335151-12-6

• 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: methyl 4-(4,4-dihydroperoxycyclohexyl)benzoate
• 英文别名: gem-bishydroperoxide
• CAS: 1335151-12-6
• 化学式: C₁₄H₁₈O₆
• 分子量: 282.293
• InChiKey: ZCROIADYPRNQRZ-UHFFFAOYSA-N

物化性质

• 沸点：
  481.1±45.0 °C(Predicted)
• 密度：
  1.32±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.81
• 重原子数：
  20.0
• 可旋转键数：
  4.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  85.22
• 氢给体数：
  2.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  methyl 4-(4,4-dihydroperoxycyclohexyl)benzoate 在 七氧化二铼 、 potassium hydroxide 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 2.5h， 生成 4-[(1''r,3''r,5''R,7''R)-dispiro[cyclohexane-1,3'-[1,2,4,5]tetroxane-6',2''-tricyclo[3.3.1.1^3,7]decan]-4-yl]benzoic acid
  参考文献：
  名称：

  Synthesis and profiling of benzylmorpholine 1,2,4,5-tetraoxane analogue N205: Towards tetraoxane scaffolds with potential for single dose cure of malaria

  摘要：

  A series of aryl carboxamide and benzylamino dispiro 1,2,4,5-tetraoxane analogues have been designed and synthesized in a short synthetic sequence from readily available starting materials. From this series of endoperoxides, molecules with in vitro IC50s versus Plasmodium falciparum (3D7) as low as 0.84 nM were identified. Based on an assessment of blood stability and in vitro microsomal stability, N205 (10a) was selected for rodent pharmacokinetic and in vivo antimalarial efficacy studies in the mouse Plasmodium berghei and Plasmodium falciparum Pf3D70087/N9 severe combined immunodeficiency (SCID) mouse models. The results indicate that the 4-benzylamino derivatives have excellent profiles with a representative of this series, N205, an excellent starting point for further lead optimization studies. (C) 2018 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2018.05.006
• 作为产物：
  描述：

  4-(4-羟基苯基)环己酮 在 甲酸 、 1,3-双(二苯基膦)丙烷 、 双氧水 、 palladium diacetate 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 12.5h， 生成 methyl 4-(4,4-dihydroperoxycyclohexyl)benzoate
  参考文献：
  名称：

  Synthesis and profiling of benzylmorpholine 1,2,4,5-tetraoxane analogue N205: Towards tetraoxane scaffolds with potential for single dose cure of malaria

  摘要：

  A series of aryl carboxamide and benzylamino dispiro 1,2,4,5-tetraoxane analogues have been designed and synthesized in a short synthetic sequence from readily available starting materials. From this series of endoperoxides, molecules with in vitro IC50s versus Plasmodium falciparum (3D7) as low as 0.84 nM were identified. Based on an assessment of blood stability and in vitro microsomal stability, N205 (10a) was selected for rodent pharmacokinetic and in vivo antimalarial efficacy studies in the mouse Plasmodium berghei and Plasmodium falciparum Pf3D70087/N9 severe combined immunodeficiency (SCID) mouse models. The results indicate that the 4-benzylamino derivatives have excellent profiles with a representative of this series, N205, an excellent starting point for further lead optimization studies. (C) 2018 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2018.05.006

文献信息

• The activity of dispiro peroxides against Fasciola hepatica
  作者：Xiaofang Wang、Qingjie Zhao、Mireille Vargas、Yuxiang Dong、Kamaraj Sriraghavan、Jennifer Keiser、Jonathan L. Vennerstrom

  DOI：10.1016/j.bmcl.2011.07.024

  日期：2011.9

  Dispiro 1,2,4-trioxanes and 1,2,4,5-tetraoxanes had superior efficacy against Fasciola hepatica than the corresponding ozonides (1,2,4-trioxolanes). For highest efficacy, spiroadamantane and carboxymethyl substructures were required. Three compounds completely cured F. hepatica-infected mice at single oral doses of 50 mg/kg and two were partially curative at single doses of 25 mg/kg. (C) 2011 Elsevier Ltd. All rights reserved.