2-(4-aminophenyl)-5-methoxy-1-oxy-indol-3-one, hydrochloride | 1583305-49-0

• 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-aminophenyl)-5-methoxy-1-oxy-indol-3-one, hydrochloride
• CAS: 1583305-49-0
• 化学式: C₁₅H₁₂N₂O₃*ClH
• 分子量: 304.733
• InChiKey: BVNOKHRSQOAZST-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.53
• 重原子数：
  21.0
• 可旋转键数：
  2.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  78.39
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为产物：
  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

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.