2-chloro-6-[4-(5-pyrimidinyl)phenylamino]-9-isopropylpurine | 1415505-20-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 2-chloro-6-[4-(5-pyrimidinyl)phenylamino]-9-isopropylpurine
• 英文别名: 2-chloro-9-propan-2-yl-N-(4-pyrimidin-5-ylphenyl)purin-6-amine
• CAS: 1415505-20-2
• 化学式: C₁₈H₁₆ClN₇
• 分子量: 365.825
• InChiKey: ZUVCFDIRJGFVPT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  81.4
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-氨基丁醇 、 2-chloro-6-[4-(5-pyrimidinyl)phenylamino]-9-isopropylpurine 在 三乙胺 作用下， 以 二甲基亚砜 为溶剂， 以40%的产率得到(R)-2-(1-hydroxybut-2-ylamino)-6-[4-(5-pyrimidinyl)phenylamino]-9-isopropylpurine
  参考文献：
  名称：

  Synthesis and evaluation of new potent inhibitors of CK1 and CDK5, two kinases involved in Alzheimer’s disease

  摘要：

  Cyclin-dependent kinase 5 (CDK5) and Casein kinase 1 (CK1) are both involved in the hyperphosphorylation of the Tau protein and in the amyloid-beta production, the two major hallmarks of Alzheimer's disease. In the present paper, we describe the synthesis and biological evaluation of new series of 2,6,9-trisubstituted purines derived from DRF53, a dual specificity inhibitor of the kinase activity of CDK5 (IC50 = 80 nM) and CK1 (IC50 = 10 nM), and are able to prevent in a dose-dependent manner the CK1-dependent production of amyloid-beta in a cell model. Several molecules (e.g., 6e, 6g, 7c) displayed potent kinase inhibitory activities against CDK5 and CK1 (IC50 values ranging from 20 to 50 nM) among which a selective inhibitor of CK1 has been identified (5a, IC50 = 60 nM). In addition, some compounds exhibit sub-micromolar activities against DYRK1A (dual specificity, tyrosine phosphorylation regulated kinase 1A), a kinase involved in Down syndrome and Alzheimer's disease (6g, IC50 = 510 nM).

  DOI：

  10.1007/s00044-012-0334-1
• 作为产物：
  描述：

  2,6-二氯-9-异丙基-9h-嘌呤 在 四(三苯基膦)钯 、 sodium carbonate 、 三乙胺 作用下， 以 1,4-二氧六环 、 水 、 正丁醇 为溶剂， 反应 24.0h， 生成 2-chloro-6-[4-(5-pyrimidinyl)phenylamino]-9-isopropylpurine
  参考文献：
  名称：

  Synthesis and evaluation of new potent inhibitors of CK1 and CDK5, two kinases involved in Alzheimer’s disease

  摘要：

  Cyclin-dependent kinase 5 (CDK5) and Casein kinase 1 (CK1) are both involved in the hyperphosphorylation of the Tau protein and in the amyloid-beta production, the two major hallmarks of Alzheimer's disease. In the present paper, we describe the synthesis and biological evaluation of new series of 2,6,9-trisubstituted purines derived from DRF53, a dual specificity inhibitor of the kinase activity of CDK5 (IC50 = 80 nM) and CK1 (IC50 = 10 nM), and are able to prevent in a dose-dependent manner the CK1-dependent production of amyloid-beta in a cell model. Several molecules (e.g., 6e, 6g, 7c) displayed potent kinase inhibitory activities against CDK5 and CK1 (IC50 values ranging from 20 to 50 nM) among which a selective inhibitor of CK1 has been identified (5a, IC50 = 60 nM). In addition, some compounds exhibit sub-micromolar activities against DYRK1A (dual specificity, tyrosine phosphorylation regulated kinase 1A), a kinase involved in Down syndrome and Alzheimer's disease (6g, IC50 = 510 nM).

  DOI：

  10.1007/s00044-012-0334-1

文献信息

• [EN] HETEROAROMATIC COMPOUNDS AND THEIR USE AS DOPAMINE D1 LIGANDS<br/>[FR] COMPOSES HETERO-AROMATIQUES ET LEUR UTILISATION COMME LIGANDS D1 DE LA DOPAMINE
  申请人：PFIZER

  公开号：WO2015162518A1

  公开（公告）日：2015-10-29

  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.

  本发明提供了部分符合Formula (I)的化合物及其药用盐；用于制备这些化合物的工艺；制备中使用的中间体；以及含有这些化合物或盐的组合物，以及它们用于治疗D1介导（或D1相关）疾病的用途，包括但不限于精神分裂症（例如其认知和消极症状）、偏执型人格障碍、认知障碍（例如与精神分裂症、阿尔茨海默病、帕金森病或药物治疗相关的认知障碍）、注意力缺陷多动障碍（ADHD）、帕金森病、焦虑和抑郁症。
• HETEROAROMATIC COMPOUNDS AND THEIR USE AS DOPAMINE D1 LIGANDS
  申请人：Pfizer Inc.

  公开号：EP3134405B1

  公开（公告）日：2019-08-28
• US9868744B2
  申请人：——

  公开号：US9868744B2

  公开（公告）日：2018-01-16
• Synthesis and evaluation of new potent inhibitors of CK1 and CDK5, two kinases involved in Alzheimer’s disease
  作者：Luc Demange、Olivier Lozach、Yoan Ferandin、Nha Thu Hoang、Laurent Meijer、Hervé Galons

  DOI：10.1007/s00044-012-0334-1

  日期：2013.7

  Cyclin-dependent kinase 5 (CDK5) and Casein kinase 1 (CK1) are both involved in the hyperphosphorylation of the Tau protein and in the amyloid-beta production, the two major hallmarks of Alzheimer's disease. In the present paper, we describe the synthesis and biological evaluation of new series of 2,6,9-trisubstituted purines derived from DRF53, a dual specificity inhibitor of the kinase activity of CDK5 (IC50 = 80 nM) and CK1 (IC50 = 10 nM), and are able to prevent in a dose-dependent manner the CK1-dependent production of amyloid-beta in a cell model. Several molecules (e.g., 6e, 6g, 7c) displayed potent kinase inhibitory activities against CDK5 and CK1 (IC50 values ranging from 20 to 50 nM) among which a selective inhibitor of CK1 has been identified (5a, IC50 = 60 nM). In addition, some compounds exhibit sub-micromolar activities against DYRK1A (dual specificity, tyrosine phosphorylation regulated kinase 1A), a kinase involved in Down syndrome and Alzheimer's disease (6g, IC50 = 510 nM).