2-((((4-碘-2-甲基苯基)氨基)亚甲基)丙二酸二乙酯 | 951006-38-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 2-((((4-碘-2-甲基苯基)氨基)亚甲基)丙二酸二乙酯
• 英文名称: diethyl 2-(((4-iodo-2-methylphenyl)amino)methylene)malonate
• 英文别名: diethyl {[(4-iodo-2-methylphenyl)amino]methylidene}propanedioate；Diethyl 2-((4-iodo-2-methylphenylamino)methylene)malonate；diethyl 2-[(4-iodo-2-methylanilino)methylidene]propanedioate
• CAS: 951006-38-5
• 化学式: C₁₅H₁₈INO₄
• 分子量: 403.217
• InChiKey: IHLDESZXQJQUAQ-UHFFFAOYSA-N

物化性质

• 沸点：
  399.1±42.0 °C(Predicted)
• 密度：
  1.532±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  21
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-((((4-碘-2-甲基苯基)氨基)亚甲基)丙二酸二乙酯 在 ammonium hydroxide 、 氯化亚砜 、 N,N-二甲基甲酰胺 、 sodium hydroxide 作用下， 以 二苯醚 、 乙醇 、 水 、 乙腈 为溶剂， 反应 3.75h， 生成 6-iodo-4-((3-methoxyphenyl)amino)-8-methylquinoline-3-carboxamide
  参考文献：
  名称：

  Repurposing Human PDE4 Inhibitors for Neglected Tropical Diseases. Evaluation of Analogs of the Human PDE4 Inhibitor GSK-256066 as Inhibitors of PDEB1 ofTrypanosoma brucei

  摘要：

  Cyclic nucleotide phosphodiesterases (PDEs) have been identified as important enzyme targets for drug development in both humans and Trypanosoma brucei, the causative agent of human African trypanosomiasis. With this in mind, we recently reported the profiling of a range of human phosphodiesterase inhibitors, showing that human PDE4 inhibitors tend to display the best potency against the trypanosomal phosphodiesterase TbrPDEB1. Among these was GSK‐256066, a potent inhibitor of human PDE4 and a weak inhibitor of TbrPDEB1. In this report, we describe the results of a structure–activity relationship study of this chemotype, leading to the discovery of analogs with improved potency against TbrPDEB1 and micromolar inhibition of T. brucei cellular growth. We rationalize the potency trends via molecular docking of the new inhibitors into a recently reported apo structure of TbrPDEB1. The studies in this article will inform future efforts in repurposing human PDE inhibitors as antitrypanosomal agents.

  DOI：

  10.1111/cbdd.12443
• 作为产物：
  描述：

  4-碘-2-甲基苯胺 、 乙氧基甲叉丙二酸二乙酯 反应 1.0h， 以98%的产率得到2-((((4-碘-2-甲基苯基)氨基)亚甲基)丙二酸二乙酯
  参考文献：
  名称：

  Repurposing Human PDE4 Inhibitors for Neglected Tropical Diseases. Evaluation of Analogs of the Human PDE4 Inhibitor GSK-256066 as Inhibitors of PDEB1 ofTrypanosoma brucei

  摘要：

  Cyclic nucleotide phosphodiesterases (PDEs) have been identified as important enzyme targets for drug development in both humans and Trypanosoma brucei, the causative agent of human African trypanosomiasis. With this in mind, we recently reported the profiling of a range of human phosphodiesterase inhibitors, showing that human PDE4 inhibitors tend to display the best potency against the trypanosomal phosphodiesterase TbrPDEB1. Among these was GSK‐256066, a potent inhibitor of human PDE4 and a weak inhibitor of TbrPDEB1. In this report, we describe the results of a structure–activity relationship study of this chemotype, leading to the discovery of analogs with improved potency against TbrPDEB1 and micromolar inhibition of T. brucei cellular growth. We rationalize the potency trends via molecular docking of the new inhibitors into a recently reported apo structure of TbrPDEB1. The studies in this article will inform future efforts in repurposing human PDE inhibitors as antitrypanosomal agents.

  DOI：

  10.1111/cbdd.12443

文献信息

• WO2007/107499
  申请人：——

  公开号：——

  公开（公告）日：——
• [EN] QUINOLINE DERIVATIVES USEFUL AS PDE4 INHIBITORS<br/>[FR] DÉRIVÉS DE QUINOLÉINE UTILES EN TANT QU'INHIBITEURS DE lA PDE4
  申请人：GLAXO GROUP LTD

  公开号：WO2007107499A1

  公开（公告）日：2007-09-27

  [EN] There is provided according to the invention novel compounds of formula (I) or pharmaceutically acceptable salts or solvates thereof. The invention also relates to the use of said compounds, compositions and medicaments, for example as inhibitors of phosphodiesterases and/or for the treatment and/or prophylaxis of diseases or conditions for which a PDE4 inhibitor is indicated, in particular inflammatory and/or allergic diseases such as chronic obstructive pulmonary disease (COPD), asthma, rheumatoid arthritis and allergic rhinitis.
  [FR] La présente invention concerne de nouveaux composés répondant à la formule (I) ou des sels ou des solvates pharmaceutiquement acceptables de ces composés. L'invention concerne également l'utilisation desdits composés, des compositions et des médicaments, en tant par exemple qu'inhibiteurs de phosphodiestérases et/ou destinés au traitement et/ou à la prophylaxie de maladies ou de pathologies pour lesquelles un inhibiteur de la PDE4 est indiqué, en particulier de maladies inflammatoires et/ou allergiques telles que la maladie pulmonaire obstructive chronique (MPOC), l'asthme, la polyarthrite rhumatoïde et la rhinite allergique.
• Repurposing Human PDE4 Inhibitors for Neglected Tropical Diseases. Evaluation of Analogs of the Human PDE4 Inhibitor GSK-256066 as Inhibitors of PDEB1 of<i>Trypanosoma brucei</i>
  作者：Stefan O. Ochiana、Nicholas D. Bland、Luca Settimo、Robert K. Campbell、Michael P. Pollastri

  DOI：10.1111/cbdd.12443

  日期：2015.5

  Cyclic nucleotide phosphodiesterases (PDEs) have been identified as important enzyme targets for drug development in both humans and Trypanosoma brucei, the causative agent of human African trypanosomiasis. With this in mind, we recently reported the profiling of a range of human phosphodiesterase inhibitors, showing that human PDE4 inhibitors tend to display the best potency against the trypanosomal phosphodiesterase TbrPDEB1. Among these was GSK‐256066, a potent inhibitor of human PDE4 and a weak inhibitor of TbrPDEB1. In this report, we describe the results of a structure–activity relationship study of this chemotype, leading to the discovery of analogs with improved potency against TbrPDEB1 and micromolar inhibition of T. brucei cellular growth. We rationalize the potency trends via molecular docking of the new inhibitors into a recently reported apo structure of TbrPDEB1. The studies in this article will inform future efforts in repurposing human PDE inhibitors as antitrypanosomal agents.