4-amino-5,6-tetramethylene-7-cyanopyrrolo<3,2-d>pyrimidine | 132994-21-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并嘧啶类
• 英文名称: 4-amino-5,6-tetramethylene-7-cyanopyrrolo<3,2-d>pyrimidine
• 英文别名: 4-amino-5,6,7,8-tetrahydro-1,3,4b-triazafluorene-9-carbonitrile；4-Amino-6,7,8,9-tetrahydropyrimido[4,5-b]indolizine-10-carbonitrile
• CAS: 132994-21-9
• 化学式: C₁₁H₁₁N₅
• 分子量: 213.242
• InChiKey: MLOHGUWGPBGUDQ-UHFFFAOYSA-N

物化性质

• 沸点：
  533.0±50.0 °C(Predicted)
• 密度：
  1.54±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  16
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  80.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-amino-5,6-tetramethylene-7-cyanopyrrolo<3,2-d>pyrimidine 、 苄磺酰氯 在 吡啶 、 4-二甲氨基吡啶 作用下， 反应 4.0h， 以16%的产率得到N-(10-cyano-6,7,8,9-tetrahydropyrimido[4,5-b]indolizin-4-yl)-1-phenylmethanesulfonamide
  参考文献：
  名称：

  Studies on Pyrrolopyrimidines as Selective Inhibitors of Multidrug-Resistance- Associated Protein in Multidrug Resistance

  摘要：

  Multidrug resistance mediated by P-glycoprotein (Pgp) or multidrug-resistance-associated protein (MRP) remains a major obstacle for successful treatment of cancer. Inhibition of Pgp and MRP transport is important for high efficacy of anticancer drugs. While several Pgp inhibitors have entered clinical trials, the development of specific MRP1 inhibitors is still in its infancy. In our screening program, we have identified a pyrrolopyrimidine (4) as a novel and selective MRP1 inhibitor. Subsequent SAR work on the 4-position of the template revealed the phenethylpiperazine side chain as a potent replacement of the benzylthio group of the lead molecule. Introduction of groups at the 2-position seems to have no detrimental effect on activity. Modifications to the nitrile group at the 7-position resulted in the identification of analogues with groups, such as amides, with superior pharmacokinetic profiles. In vivo efficacy has been demonstrated by xenograft studies on selected compounds.

  DOI：

  10.1021/jm031011g
• 作为产物：
  描述：

  5,6,7,8-tetrahydro-2-(N,N-dimethylaminomethylene)amino-3-ethoxycarbonyl-1-cyanoindolizine 在 sodium hydroxide 、 氨 、 三乙胺盐酸盐 、 三氯氧磷 作用下， 以 乙醇 为溶剂， 反应 13.0h， 生成 4-amino-5,6-tetramethylene-7-cyanopyrrolo<3,2-d>pyrimidine
  参考文献：
  名称：

  Synthesis and biological activity of condensed pyrrolo[3,2-d]pyrimidines

  摘要：

  DOI：

  10.1007/bf00766579