2-氯-6-[4-(3-吡啶基)苯基氨基]-9-异丙基嘌呤 | 1056016-78-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 中文名称: 2-氯-6-[4-(3-吡啶基)苯基氨基]-9-异丙基嘌呤
• 英文名称: 2-chloro-6-[4-(3-pyridyl)phenylamino]-9-iso-propylpurine
• 英文别名: 2-chloro-9-propan-2-yl-N-(4-pyridin-3-ylphenyl)purin-6-amine
• CAS: 1056016-78-4
• 化学式: C₁₉H₁₇ClN₆
• 分子量: 364.837
• InChiKey: RXHQBBWWEOAVQM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  68.5
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-氨基丁醇 、 2-氯-6-[4-(3-吡啶基)苯基氨基]-9-异丙基嘌呤 在 三正丁胺 作用下， 以 二甲基亚砜 为溶剂， 反应 3.0h， 以79%的产率得到(R)-2-(1-hydroxy-but-2-ylamino)-6-[4-(3-pyridyl)phenylamino]-9-iso-propylpurine
  参考文献：
  名称：

  Roscovitine-Derived, Dual-Specificity Inhibitors of Cyclin-Dependent Kinases and Casein Kinases 1

  摘要：

  Cyclin-dependent kinases (CDKs) and casein kinases 1 (CK 1) are involved in the two key molecular features of Alzheimer's disease, production of amyloid-beta peptides (extracellular plaques) and hyper-phosphorylation of Tau (intracellular neurofibrillary tangles). A series of 2,6,9-trisubstituted purines, structurally related to the CDK inhibitor roscovitine, have been synthesized. They mainly differ by the substituent on the C-6 position. These compounds were screened for kinase inhibitory activities and antiproliferative effects. Several biaryl derivatives displayed potent inhibition of both CDKs and CK1. In particular, derivative 13a was a potent inhibitor of CDK1/cyclin B (IC50: 220 nM), CDK5/p25 (IC50: 80 nM), and CK1 (IC50: 14 nM). Modeling of these molecules into the ATP-binding pocket of CK1 delta provided a rationale for the increased selectivity toward this kinase. 13a was able to prevent the CK1-dependent production of anyloid-beta in a cell model. CDK/CK1 dual-specificity inhibitors may have important applications in Alzheimer's disease and cancers.

  DOI：

  10.1021/jm800109e
• 作为产物：
  描述：

  3-溴吡啶 、 2-氯-9-(1-甲基乙基)-N-[4-(4,4,5,5-四甲基-1,3,2-二噁硼烷-2-基)苯基]-9H-嘌呤-6-胺 在 四(三苯基膦)钯 、 sodium carbonate 作用下， 以 1,4-二氧六环 、 水 为溶剂， 以52%的产率得到2-氯-6-[4-(3-吡啶基)苯基氨基]-9-异丙基嘌呤
  参考文献：
  名称：

  Roscovitine-Derived, Dual-Specificity Inhibitors of Cyclin-Dependent Kinases and Casein Kinases 1

  摘要：

  Cyclin-dependent kinases (CDKs) and casein kinases 1 (CK 1) are involved in the two key molecular features of Alzheimer's disease, production of amyloid-beta peptides (extracellular plaques) and hyper-phosphorylation of Tau (intracellular neurofibrillary tangles). A series of 2,6,9-trisubstituted purines, structurally related to the CDK inhibitor roscovitine, have been synthesized. They mainly differ by the substituent on the C-6 position. These compounds were screened for kinase inhibitory activities and antiproliferative effects. Several biaryl derivatives displayed potent inhibition of both CDKs and CK1. In particular, derivative 13a was a potent inhibitor of CDK1/cyclin B (IC50: 220 nM), CDK5/p25 (IC50: 80 nM), and CK1 (IC50: 14 nM). Modeling of these molecules into the ATP-binding pocket of CK1 delta provided a rationale for the increased selectivity toward this kinase. 13a was able to prevent the CK1-dependent production of anyloid-beta in a cell model. CDK/CK1 dual-specificity inhibitors may have important applications in Alzheimer's disease and cancers.

  DOI：

  10.1021/jm800109e

文献信息

• HETEROAROMATIC COMPOUNDS AND THEIR USE AS DOPAMINE D1 LIGANDS
  申请人：PFIZER INC.

  公开号：US20170037053A1

  公开（公告）日：2017-02-09

  The present invention provides, in part, compounds of Formula (I) and pharmaceutically acceptable salts thereof; processes for the preparation of; intermediates used in the preparation of; and compositions containing such compounds or salts, and their uses for treating D1-mediated (or D1-associated) disorders including, e.g., schizophrenia (e.g., its cognitive and negative symptoms), schizotypal personality disorder, cognitive impairment (e.g., cognitive impairment associated with schizophrenia, AD, PD, or pharmacotherapy therapy), ADHD, Parkinson's disease, anxiety, and depression.
• US9868744B2
  申请人：——

  公开号：US9868744B2

  公开（公告）日：2018-01-16