1-{4-[2-(3,4-difluoro-phenyl)ethyl]-piperazin-1-yl}-9-pyridin-4-ylmethyl-9H-2,4,9-triaza-fluorene-5-carboxylic acid amide

• 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: 1-{4-[2-(3,4-difluoro-phenyl)ethyl]-piperazin-1-yl}-9-pyridin-4-ylmethyl-9H-2,4,9-triaza-fluorene-5-carboxylic acid amide
• 英文别名: 4-{4-[2-(3,4-Difluoro-phenyl)-ethyl]-piperazin-1-yl}-5-pyridin-4-ylmethyl-5H-pyrimido[5,4-b]indole-9-carboxylic acid amide；4-[4-[2-(3,4-difluorophenyl)ethyl]piperazin-1-yl]-5-(pyridin-4-ylmethyl)pyrimido[5,4-b]indole-9-carboxamide
• 化学式: C₂₉H₂₇F₂N₇O
• 分子量: 527.576
• InChiKey: BLIMNWSQDQYNMP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  39
• 可旋转键数：
  7
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  93.2
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  3-氟邻苯二腈 在 4-二甲氨基吡啶 、 sodium hydroxide 、 氨 、 双氧水 、 三乙胺盐酸盐 、 sodium hydride 、 potassium carbonate 、 三乙胺 、 三氯氧磷 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 74.67h， 生成 1-{4-[2-(3,4-difluoro-phenyl)ethyl]-piperazin-1-yl}-9-pyridin-4-ylmethyl-9H-2,4,9-triaza-fluorene-5-carboxylic acid amide
  参考文献：
  名称：

  Design and Synthesis of New Templates Derived from Pyrrolopyrimidine as Selective Multidrug-Resistance-Associated Protein Inhibitors in Multidrug Resistance

  摘要：

  In our continued effort to identify selective MRP1 modulators, we have developed two novel templates, 3 and 4, through rational drug design by identifying the key pharmacophore interaction at the 7-position of the pyrrolopyrimidine template 1. Further synthesis and SAR work on these novel templates gave a number of potent MRP1 modulators with great selectivity against Pgp. Additional studies to reduce the CYP3A4 inhibition are also reported. Several compounds of these classes were subjected to in vivo xenograft studies and in vivo efficacies were demonstrated.

  DOI：

  10.1021/jm0310129

文献信息

• Design and Synthesis of New Templates Derived from Pyrrolopyrimidine as Selective Multidrug-Resistance-Associated Protein Inhibitors in Multidrug Resistance
  作者：Shouming Wang、Nan Chi Wan、John Harrison、Warren Miller、Irina Chuckowree、Sukhjit Sohal、Timothy C. Hancox、Stewart Baker、Adrian Folkes、Francis Wilson、Deanne Thompson、Simon Cocks、Hayley Farmer、Anthony Boyce、Caroline Freathy、Jan Broadbridge、John Scott、Paul Depledge、Richard Faint、Prakash Mistry、Peter Charlton

  DOI：10.1021/jm0310129

  日期：2004.3.1

  In our continued effort to identify selective MRP1 modulators, we have developed two novel templates, 3 and 4, through rational drug design by identifying the key pharmacophore interaction at the 7-position of the pyrrolopyrimidine template 1. Further synthesis and SAR work on these novel templates gave a number of potent MRP1 modulators with great selectivity against Pgp. Additional studies to reduce the CYP3A4 inhibition are also reported. Several compounds of these classes were subjected to in vivo xenograft studies and in vivo efficacies were demonstrated.