2-氯-6-苯基-9-异丙基嘌呤 | 1056015-98-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 中文名称: 2-氯-6-苯基-9-异丙基嘌呤
• 英文名称: 2-chloro-9-isopropyl-6-phenyl-9H-purine
• 英文别名: 2-chloro-6-phenyl-9-iso-propylpurine；2-Chloro-6-phenyl-9-propan-2-ylpurine
• CAS: 1056015-98-5
• 化学式: C₁₄H₁₃ClN₄
• 分子量: 272.737
• InChiKey: FMDWTQNSXCZGMJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  43.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-氨基丁醇 、 2-氯-6-苯基-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56%的产率得到(R)-2-(1-hydroxy-but-2-ylamino)-6-phenyl-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：

  苯硼酸频哪醇酯 、 2,6-二氯-9-异丙基-9h-嘌呤 在 四(三苯基膦)钯 、 sodium carbonate 作用下， 以 1,4-二氧六环 、 水 为溶剂， 以87%的产率得到2-氯-6-苯基-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

• 嘧啶并五元杂环类化合物及其作为突变型IDH2抑制剂的用途
  申请人：上海仕谱生物科技有限公司

  公开号：CN111825674A

  公开（公告）日：2020-10-27

  本发明涉及一种嘧啶并五元杂环类化合物及其作为突变型IDH2抑制剂的用途，具体地，本发明公开了一种可作为突变型IDH2抑制剂的嘧啶并五元杂环类化合物、或其立体异构体或互变异构体、或药学上可接受的盐、水合物或溶剂化物。本发明还涉及包含上述化合物的药物组合物及其用于制备预防和/或治疗突变型IDH2介导的疾病的药物的用途。
• PYRIMIDO FIVE-MEMBERED HETEROCYCLIC COMPOUND AND USE THEREOF AS MUTANT IDH2 INHIBITOR
  申请人：Epitas Biosciences (Shanghai) Co., Ltd.

  公开号：EP3967691A1

  公开（公告）日：2022-03-16

  The present invention relates to a pyrimido five-membered heterocyclic compound and use thereof as a mutant IDH2 inhibitor. Specifically, disclosed in the present invention are a pyrimido five-membered heterocyclic compound capable of serving as a mutant IDH2 inhibitor, or a stereoisomer or a tautomer, or a pharmaceutically acceptable salt, a hydrate or a solvate thereof. The present invention also relates to a pharmaceutical composition comprising the compound, and use thereof in the prepration of a medicament for preventing and/or treating a disease mediated by mutant IDH2.

  本发明涉及一种嘧啶类五元杂环化合物及其作为突变型 IDH2 抑制剂的用途。具体地说，本发明公开了一种能够作为突变体IDH2抑制剂的嘧啶类五元杂环化合物，或其立体异构体或同系物，或其药学上可接受的盐、水合物或溶液。本发明还涉及一种包含该化合物的药物组合物，以及将其用于制备预防和/或治疗由突变体IDH2介导的疾病的药物。
• [EN] PYRIMIDO FIVE-MEMBERED HETEROCYCLIC COMPOUND AND USE THEREOF AS MUTANT IDH2 INHIBITOR<br/>[FR] COMPOSÉ HÉTÉROCYCLIQUE À CINQ CHAÎNONS À BASE DE PYRIMIDO ET SON UTILISATION EN TANT QU'INHIBITEUR D'IDH2 MUTANT<br/>[ZH] 嘧啶并五元杂环类化合物及其作为突变型IDH2抑制剂的用途
  申请人：EPITAS BIOSCIENCES SHANGHAI CO LTD

  公开号：WO2020215998A1

  公开（公告）日：2020-10-29

  本发明涉及一种嘧啶并五元杂环类化合物及其作为突变型IDH2抑制剂的用途，具体地，本发明公开了一种可作为突变型IDH2抑制剂的嘧啶并五元杂环类化合物、或其立体异构体或互变异构体、或药学上可接受的盐、水合物或溶剂化物。本发明还涉及包含上述化合物的药物组合物及其用于制备预防和/或治疗突变型IDH2介导的疾病的药物的用途。