2-chloro-9-(3,5-difluorophenyl)-N-ethyl-9H-purin-6-amine | 1199523-49-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-chloro-9-(3,5-difluorophenyl)-N-ethyl-9H-purin-6-amine
• 英文别名: 2-chloro-9-(3,5-difluorophenyl)-N-ethylpurin-6-amine
• CAS: 1199523-49-3
• 化学式: C₁₃H₁₀ClF₂N₅
• 分子量: 309.706
• InChiKey: MVRYXPLJINHSBI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 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-9-(3,5-difluorophenyl)-N-ethyl-9H-purin-6-amine 以 二甲基亚砜 为溶剂， 以48%的产率得到9-(3,5-difluorophenyl)-6-(ethylamino)-9H-purine-2-carbonitrile
  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：

  2,6-dichloro-9-(3,5-difluorophenyl)-9H-purine 、 乙胺 在 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以83%的产率得到2-chloro-9-(3,5-difluorophenyl)-N-ethyl-9H-purin-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

• [EN] SUBSTITUTED TRIAZINE AND PURINE COMPOUNDS, METHODS OF INHIBITING CRUZAIN AND RHODESAIN AND METHODS OF TREATING CHAGAS DISEASE AND AFRICAN TRYPANOSOMIASIS<br/>[FR] COMPOSÉS DE TRIAZINE ET DE PURINE SUBSTITUÉES, MÉTHODES D'INHIBITION DE CRUZAÏNE ET DE RHODÉSAÏNE ET MÉTHODES DE TRAITEMENT DE LA MALADIE DE CHAGAS ET DE LA TRYPANOSOMIASE AFRICAINE
  申请人：GOVERNMENT OF THE U S A AS REP

  公开号：WO2010059418A1

  公开（公告）日：2010-05-27

  The invention provides for novel triazine and purine compounds ( II ) that are useful for the treatment and prevention of mammalian protozoal diseases, including Af rican trypanosomiasis and Chagas disease.

  这项发明提供了一种新型的三嗪和嘌呤化合物（II），可用于治疗和预防哺乳动物原生动物疾病，包括非洲锥虫病和充血性心脏病。
• 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.