(10-(3-hydroxy-4-(methoxycarbonyl)phenoxy)decyl)triphenylphosphonium bromide

• 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: (10-(3-hydroxy-4-(methoxycarbonyl)phenoxy)decyl)triphenylphosphonium bromide
• 英文别名: 10-(3-Hydroxy-4-methoxycarbonylphenoxy)decyl-triphenylphosphanium;bromide；10-(3-hydroxy-4-methoxycarbonylphenoxy)decyl-triphenylphosphanium;bromide
• 化学式: Br*C₃₆H₄₂O₄P
• 分子量: 649.605
• InChiKey: SIODDCCZGLDMAH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.68
• 重原子数：
  42
• 可旋转键数：
  17
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  55.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (10-(3-hydroxy-4-(methoxycarbonyl)phenoxy)decyl)triphenylphosphonium bromide 在 水 、 potassium carbonate 作用下， 以 甲醇 为溶剂， 反应 67.0h， 以100%的产率得到(10-(4-carboxy-3-hydroxyphenoxy)decyl)triphenylphosphonium bromide
  参考文献：
  名称：

  SAR of 4-Alkoxybenzoic Acid Inhibitors of the Trypanosome Alternative Oxidase

  摘要：

  The SAR of 4-hydroxybenzaldehyde inhibitors of the trypanosome alternative oxidase (TAO), a critical enzyme for the respiration of bloodstream forms of trypanosomes, was investigated. Replacing the aldehyde group with a methyl ester resulted in a 10-fold increase in TAO inhibition and activity against T. brucei. Remarkably, two analogues containing the 2-hydroxy-6-methyl scaffold (9e and 16e) displayed single digit nanomolar TAO inhibition, which constitute the most potent 4-alkoxybenzoic acid derivatives described to date. 9e was 50-times more potent against TAO and 10-times more active against T. brucei compared to its benzaldehyde analogue 1. The farnesyl derivative 16e was as potent a TAO inhibitor as ascofuranone with IC50 = 3.1 nM. Similar to ascofuranone derivatives, the 2-hydroxy and 6-methyl groups seemed essential for low nanomolar TAO inhibition of acid derivatives, suggesting analogous binding interactions with the TAO active site.

  DOI：

  10.1021/acsmedchemlett.8b00282
• 作为产物：
  描述：

  2,4-二羟基苯甲酸甲酯 在 碳酸氢钠 作用下， 以 乙腈 为溶剂， 反应 336.0h， 生成 (10-(3-hydroxy-4-(methoxycarbonyl)phenoxy)decyl)triphenylphosphonium bromide
  参考文献：
  名称：

  SAR of 4-Alkoxybenzoic Acid Inhibitors of the Trypanosome Alternative Oxidase

  摘要：

  The SAR of 4-hydroxybenzaldehyde inhibitors of the trypanosome alternative oxidase (TAO), a critical enzyme for the respiration of bloodstream forms of trypanosomes, was investigated. Replacing the aldehyde group with a methyl ester resulted in a 10-fold increase in TAO inhibition and activity against T. brucei. Remarkably, two analogues containing the 2-hydroxy-6-methyl scaffold (9e and 16e) displayed single digit nanomolar TAO inhibition, which constitute the most potent 4-alkoxybenzoic acid derivatives described to date. 9e was 50-times more potent against TAO and 10-times more active against T. brucei compared to its benzaldehyde analogue 1. The farnesyl derivative 16e was as potent a TAO inhibitor as ascofuranone with IC50 = 3.1 nM. Similar to ascofuranone derivatives, the 2-hydroxy and 6-methyl groups seemed essential for low nanomolar TAO inhibition of acid derivatives, suggesting analogous binding interactions with the TAO active site.

  DOI：

  10.1021/acsmedchemlett.8b00282

文献信息

• SAR of 4-Alkoxybenzoic Acid Inhibitors of the Trypanosome Alternative Oxidase
  作者：Alejandro Meco-Navas、Godwin U. Ebiloma、Ana Martín-Domínguez、Irene Martínez-Benayas、Eduardo J. Cueto-Díaz、Amani Saud Alhejely、Emmanuel O. Balogun、Machi Saito、Miho Matsui、Natsumi Arai、Tomoo Shiba、Shigeharu Harada、Harry P. de Koning、Christophe Dardonville

  DOI：10.1021/acsmedchemlett.8b00282

  日期：2018.9.13

  The SAR of 4-hydroxybenzaldehyde inhibitors of the trypanosome alternative oxidase (TAO), a critical enzyme for the respiration of bloodstream forms of trypanosomes, was investigated. Replacing the aldehyde group with a methyl ester resulted in a 10-fold increase in TAO inhibition and activity against T. brucei. Remarkably, two analogues containing the 2-hydroxy-6-methyl scaffold (9e and 16e) displayed single digit nanomolar TAO inhibition, which constitute the most potent 4-alkoxybenzoic acid derivatives described to date. 9e was 50-times more potent against TAO and 10-times more active against T. brucei compared to its benzaldehyde analogue 1. The farnesyl derivative 16e was as potent a TAO inhibitor as ascofuranone with IC50 = 3.1 nM. Similar to ascofuranone derivatives, the 2-hydroxy and 6-methyl groups seemed essential for low nanomolar TAO inhibition of acid derivatives, suggesting analogous binding interactions with the TAO active site.