2-chloro-N-(3,5-difluorophenyl)-9-ethylpurin-6-amine | 1415016-26-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: 2-chloro-N-(3,5-difluorophenyl)-9-ethylpurin-6-amine
• CAS: 1415016-26-0
• 化学式: C₁₃H₁₀ClF₂N₅
• 分子量: 309.706
• InChiKey: IFFPSJKAAWNSFA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  55.6
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  potassium cyanide 、 2-chloro-N-(3,5-difluorophenyl)-9-ethylpurin-6-amine 以 二甲基亚砜 为溶剂， 以35 mg的产率得到MMV676881
  参考文献：
  名称：

  Identification and Optimization of Inhibitors of Trypanosomal Cysteine Proteases: Cruzain, Rhodesain, and TbCatB

  摘要：

  Trypanosoma cruzi and Trypanosoma brucei are parasites that cause Chagas' disease and African sleeping sickness, respectively. Both parasites rely oil essential cysteine proteases for survival: cruzain for T. cruzi and TbCatB/rhodesain for T. brucei. A recent quantitative high-throughput screen of cruzain identified triazine nitriles. which are known inhibitors of other cysteine proteases, its reversible inhibitors of the enzyme. Structural modifications detailed herein, including core scaffold modification from triazine to purine, improved the in vitro potency against both cruzain and rhodesain by 350-fold, while also gaining activity against T. brucei parasites. Selected compounds were screened against it panel of human cysteine and serine proteases to determine selectivity, and it cocrystal was obtained of our most potent analogue bound to cruzain.

  DOI：

  10.1021/jm901069a
• 作为产物：
  描述：

  3,5-二氟苯胺 、 2,6-dichloro-9-ethyl-9H-purine 在 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 2-chloro-N-(3,5-difluorophenyl)-9-ethylpurin-6-amine
  参考文献：
  名称：

  Identification and Optimization of Inhibitors of Trypanosomal Cysteine Proteases: Cruzain, Rhodesain, and TbCatB

  摘要：

  Trypanosoma cruzi and Trypanosoma brucei are parasites that cause Chagas' disease and African sleeping sickness, respectively. Both parasites rely oil essential cysteine proteases for survival: cruzain for T. cruzi and TbCatB/rhodesain for T. brucei. A recent quantitative high-throughput screen of cruzain identified triazine nitriles. which are known inhibitors of other cysteine proteases, its reversible inhibitors of the enzyme. Structural modifications detailed herein, including core scaffold modification from triazine to purine, improved the in vitro potency against both cruzain and rhodesain by 350-fold, while also gaining activity against T. brucei parasites. Selected compounds were screened against it panel of human cysteine and serine proteases to determine selectivity, and it cocrystal was obtained of our most potent analogue bound to cruzain.

  DOI：

  10.1021/jm901069a

文献信息

• Identification and Optimization of Inhibitors of Trypanosomal Cysteine Proteases: Cruzain, Rhodesain, and TbCatB
  作者：Bryan T. Mott、Rafaela S. Ferreira、Anton Simeonov、Ajit Jadhav、Kenny Kean-Hooi Ang、William Leister、Min Shen、Julia T. Silveira、Patricia S. Doyle、Michelle R. Arkin、James H. McKerrow、James Inglese、Christopher P. Austin、Craig J. Thomas、Brian K. Shoichet、David J. Maloney

  DOI：10.1021/jm901069a

  日期：2010.1.14

  Trypanosoma cruzi and Trypanosoma brucei are parasites that cause Chagas' disease and African sleeping sickness, respectively. Both parasites rely oil essential cysteine proteases for survival: cruzain for T. cruzi and TbCatB/rhodesain for T. brucei. A recent quantitative high-throughput screen of cruzain identified triazine nitriles. which are known inhibitors of other cysteine proteases, its reversible inhibitors of the enzyme. Structural modifications detailed herein, including core scaffold modification from triazine to purine, improved the in vitro potency against both cruzain and rhodesain by 350-fold, while also gaining activity against T. brucei parasites. Selected compounds were screened against it panel of human cysteine and serine proteases to determine selectivity, and it cocrystal was obtained of our most potent analogue bound to cruzain.