2-(4-dimethylaminophenyl)-5-methoxy-1-oxyindol-3-one | 1133205-20-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 2-(4-dimethylaminophenyl)-5-methoxy-1-oxyindol-3-one
• 英文别名: 2-[4-(Dimethylamino)phenyl]-5-methoxy-1-oxidoindol-1-ium-3-one
• CAS: 1133205-20-5
• 化学式: C₁₇H₁₆N₂O₃
• 分子量: 296.326
• InChiKey: JQAUFPPUDCBLRA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  58.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(4-dimethylaminophenyl)-5-methoxy-1-oxyindol-3-one 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 反应 1.0h， 以93%的产率得到2-(4-aminophenyl)-5-methoxy-1-oxy-indol-3-one, hydrochloride
  参考文献：
  名称：

  Amino derivatives of indolone-N-oxide: Preparation and antiplasmodial properties

  摘要：

  There is an urgent need for new antimalarial drugs with novel mechanisms of action on novel targets. Indolone-N-oxides (INODs) display antimalarial properties in vitro and in vivo, but identified leads such as 6-(4-chloro-phenyl)-5-oxy-[1,3]dioxolo[4,5-f]indol-7-one 1, suffer from very poor aqueous solubility. In this study, structural modifications have been made by introducing various amino and bulky groups to produce sufficiently water soluble and active compounds for further pharmacological and pharmacokinetic studies. We report here the preparation of twelve novel amino derivatives and their anti-plasmodial activities including those of two other structurally known compounds. The 5-methoxy-2-(4-morpholin-4-yl-phenyl)-1-oxy-indol-3-one, 9, has the highest antiplasmodial activity in vitro (IC50 = 6.5 nM; FcB1 strain) and selectivity index (SI (CC(50)MCF7/IC50 FcB1) = 4538.5). The 6-amino-2-(4-chloro-phenyl)-1-oxy-indol-3-one, 14, (IC50 = 183 nM; SI = 60), is an excellent candidate for further mechanistic studies. Indeed, this is structurally the closest analogue to the current lead, 1, bearing an NH2 group at R-2 offering possibilities for functionalization and labeling. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.02.038
• 作为产物：
  描述：

  N,N-二甲基-4-[(三甲基甲硅烷基)乙炔基]苯胺 在 bis-triphenylphosphine-palladium(II) chloride 、 双(乙腈)氯化钯(II) 、 copper(l) iodide 、 potassium carbonate 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 、 乙腈 为溶剂， 生成 2-(4-dimethylaminophenyl)-5-methoxy-1-oxyindol-3-one
  参考文献：
  名称：

  2-Aryl-3H-indol-3-ones: Synthesis, electrochemical behaviour and antiplasmodial activities

  摘要：

  The synthesis of indolone derivatives and their antiplasmodial activity in vitro against Plasmodium falciparum at the blood stage are described. The 2-aryl-3H-indol-3-ones were synthesized via deoxygenation of indolone-N-oxides. Electrochemical behaviour, antiplasmodial activity and cytotoxicity on human tumor cell lines were compared to those of indolone-N-oxides. The antiplasmodial IC50 (concentrations at 50% inhibition) of these compounds ranged between 49 and 1327 nM. Among them, the 2(4-dimethylaminophenyl)-5-methoxy-indol-3-one, 7, had the best antiplasmodial activity in vitro (IC50 = 49 nM; FcB1 strain) and selectivity index (SI (CC50 MCF7/IC50 FcB1) = 423.4). Thus, the hits identified in this deoxygenated series correspond to their structural homologs in the N-oxide series with comparable electrochemical behaviour at the nitrogen-carbon double bond. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.03.059

文献信息

• Amino derivatives of indolone-N-oxide: Preparation and antiplasmodial properties
  作者：Ennaji Najahi、Nambinina V. Rakotoarivelo、Alexis Valentin、Françoise Nepveu

  DOI：10.1016/j.ejmech.2014.02.038

  日期：2014.4

  There is an urgent need for new antimalarial drugs with novel mechanisms of action on novel targets. Indolone-N-oxides (INODs) display antimalarial properties in vitro and in vivo, but identified leads such as 6-(4-chloro-phenyl)-5-oxy-[1,3]dioxolo[4,5-f]indol-7-one 1, suffer from very poor aqueous solubility. In this study, structural modifications have been made by introducing various amino and bulky groups to produce sufficiently water soluble and active compounds for further pharmacological and pharmacokinetic studies. We report here the preparation of twelve novel amino derivatives and their anti-plasmodial activities including those of two other structurally known compounds. The 5-methoxy-2-(4-morpholin-4-yl-phenyl)-1-oxy-indol-3-one, 9, has the highest antiplasmodial activity in vitro (IC50 = 6.5 nM; FcB1 strain) and selectivity index (SI (CC(50)MCF7/IC50 FcB1) = 4538.5). The 6-amino-2-(4-chloro-phenyl)-1-oxy-indol-3-one, 14, (IC50 = 183 nM; SI = 60), is an excellent candidate for further mechanistic studies. Indeed, this is structurally the closest analogue to the current lead, 1, bearing an NH2 group at R-2 offering possibilities for functionalization and labeling. (C) 2014 Elsevier Masson SAS. All rights reserved.
• 2-Aryl-3H-indol-3-ones: Synthesis, electrochemical behaviour and antiplasmodial activities
  作者：Ennaji Najahi、Alexis Valentin、Paul-Louis Fabre、Karine Reybier、Françoise Nepveu

  DOI：10.1016/j.ejmech.2014.03.059

  日期：2014.5

  The synthesis of indolone derivatives and their antiplasmodial activity in vitro against Plasmodium falciparum at the blood stage are described. The 2-aryl-3H-indol-3-ones were synthesized via deoxygenation of indolone-N-oxides. Electrochemical behaviour, antiplasmodial activity and cytotoxicity on human tumor cell lines were compared to those of indolone-N-oxides. The antiplasmodial IC50 (concentrations at 50% inhibition) of these compounds ranged between 49 and 1327 nM. Among them, the 2(4-dimethylaminophenyl)-5-methoxy-indol-3-one, 7, had the best antiplasmodial activity in vitro (IC50 = 49 nM; FcB1 strain) and selectivity index (SI (CC50 MCF7/IC50 FcB1) = 423.4). Thus, the hits identified in this deoxygenated series correspond to their structural homologs in the N-oxide series with comparable electrochemical behaviour at the nitrogen-carbon double bond. (C) 2014 Elsevier Masson SAS. All rights reserved.