6-甲基氨基-9H-嘌呤-2-甲腈 | 945565-57-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 中文名称: 6-甲基氨基-9H-嘌呤-2-甲腈
• 英文名称: 6-methylamino-9H-purine-2-carbonitrile
• 英文别名: 6-(Methylamino)-9H-purine-2-carbonitrile；6-(methylamino)-7H-purine-2-carbonitrile
• CAS: 945565-57-1
• 化学式: C₇H₆N₆
• 分子量: 174.165
• InChiKey: HHSWGJDRZWRMNR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  90.3
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6-甲基氨基-9H-嘌呤-2-甲腈 在 偶氮二甲酸二异丙酯 、 三苯基膦 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 28.5h， 生成 phosphoric acid mono-[4-(2-cyano-6-methylaminopurin-9-yl)-1-phosphonooxymethyl-bicyclo[3.1.0]hex-2-yl] ester
  参考文献：
  名称：

  P2Y₁ Antagonists:  Combining Receptor-Based Modeling and QSAR for a Quantitative Prediction of the Biological Activity Based on Consensus Scoring

  摘要：

  P2Y(1) is an ADP-activated G protein-coupled receptor (GPCR). Its antagonists impede platelet aggregation in vivo and are potential antithrombotic agents. Combining ligand and structure-based modeling we generated a consensus model (LIST-CM) correlating antagonist structures with their potencies. We docked 45 antagonists into our rhodopsin-based human P2Y(1) homology model and calculated docking scores and free binding energies with the Linear Interaction Energy (LIE) method in continuum-solvent. The resulting alignment was also used to build QSAR based on CoMFA, CoMSIA, and molecular descriptors. To benefit from the strength of each technique and compensate for their limitations, we generated our LIST-CM with a PLS regression based on the predictions of each methodology. A test set featuring untested substituents was synthesized and assayed in inhibition of 2-MeSADP-stimulated PLC activity and in radioligand binding. LIST-CM outperformed internal and external predictivity of any individual model to predict accurately the potency of 75% of the test set.

  DOI：

  10.1021/jm0700971
• 作为产物：
  描述：

  6-chloro-2-iodopurin-9-yl-methyl 2,2-dimethylpropionate 在 tris(dibenzylideneacetone)dipalladium(0) chloroform complex 三(2-呋喃基)膦 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 120.0h， 生成 6-甲基氨基-9H-嘌呤-2-甲腈
  参考文献：
  名称：

  P2Y₁ Antagonists:  Combining Receptor-Based Modeling and QSAR for a Quantitative Prediction of the Biological Activity Based on Consensus Scoring

  摘要：

  P2Y(1) is an ADP-activated G protein-coupled receptor (GPCR). Its antagonists impede platelet aggregation in vivo and are potential antithrombotic agents. Combining ligand and structure-based modeling we generated a consensus model (LIST-CM) correlating antagonist structures with their potencies. We docked 45 antagonists into our rhodopsin-based human P2Y(1) homology model and calculated docking scores and free binding energies with the Linear Interaction Energy (LIE) method in continuum-solvent. The resulting alignment was also used to build QSAR based on CoMFA, CoMSIA, and molecular descriptors. To benefit from the strength of each technique and compensate for their limitations, we generated our LIST-CM with a PLS regression based on the predictions of each methodology. A test set featuring untested substituents was synthesized and assayed in inhibition of 2-MeSADP-stimulated PLC activity and in radioligand binding. LIST-CM outperformed internal and external predictivity of any individual model to predict accurately the potency of 75% of the test set.

  DOI：

  10.1021/jm0700971

文献信息

• [EN] BETA-D-2'-DEOXY-2'-ALPHA-FLUORO-2'-BETA-C-SUBSTITUTED-4'-FLUORO-N6-SUBSTITUTED-6-AMINO-2-SUBSTITUTED PURINE NUCLEOTIDES FOR THE TREATMENT OF HEPATITIS C VIRUS INFECTION<br/>[FR] NUCLÉOTIDES DE PURINE BETA-D-2'-DEOXY-2'-ALPHA-FLUORO-2'-BETA-C-SUBSTITUÉ-4'-FLUORO-N6-SUBSTITUÉ-6-AMINO-2-SUBSTITUÉ POUR LE TRAITEMENT DE L'INFECTION PAR LE VIRUS DE L'HÉPATITE C
  申请人：ATEA PHARMACEUTICALS INC

  公开号：WO2018013937A1

  公开（公告）日：2018-01-18

  Compounds of Formula I, Formula II, Formula III, Formula IV, Formula V, Formula VI, Formula VII, Formula VIII, Formula IX and Formula X that are highly active against the HCV virus when administered in an effective amount to a host in need thereof. The host can be a human or any animal that carries the viral infection. Methods of treating a subject suffering from a condition related to viral infections are also provided.

  当以有效剂量给予宿主时，化合物I、化合物II、化合物III、化合物IV、化合物V、化合物VI、化合物VII、化合物VIII、化合物IX和化合物X对HCV病毒具有高活性。宿主可以是患有病毒感染的人类或任何动物。还提供了治疗与病毒感染相关疾病的方法。