2-amino-6-chloro-9-isobutyl-9H-purine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: 2-amino-6-chloro-9-isobutyl-9H-purine
• 英文别名: 6-Chloro-9-(2-methylpropyl)purin-2-amine；6-chloro-9-(2-methylpropyl)purin-2-amine
• 化学式: C₉H₁₂ClN₅
• 分子量: 225.681
• InChiKey: VGLZYBZQGIVEBV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  69.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-amino-6-chloro-9-isobutyl-9H-purine 在 氯化亚砜 、 三乙胺 作用下， 以 正丁醇 为溶剂， 反应 20.5h， 生成 methyl 7-((2-amino-9-isobutyl-9H-purin-6-yl)amino)heptanoate
  参考文献：
  名称：

  设计和合成新一代取代嘌呤异羟肟酸酯类似物作为组蛋白脱乙酰基酶抑制剂

  摘要：

  组蛋白脱乙酰基酶抑制剂已被证明在治疗癌症方面具有巨大潜力。最近，我们根据先前的研究设计并修饰了一系列取代的嘌呤异羟肟酸酯类似物，作为有效的HDAC抑制剂。研究了目标化合物的体外HDAC抑制活性和抗增殖活性。结果表明，这些化合物可有效抑制HDAC，对肿瘤细胞具有明显的抗增殖活性。可能地，目标化合物4m和4n在酶抑制活性和细胞抗增殖活性测定方面均优于SAHA。

  DOI：

  10.1016/j.bmc.2016.02.005
• 作为产物：
  描述：

  溴代异丁烷 、 2-氨基-6-氯嘌呤 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.5h， 生成 2-amino-6-chloro-7-isobutyl-7H-purine 、 2-amino-6-chloro-9-isobutyl-9H-purine
  参考文献：
  名称：

  The discovery of purine-based agents targeting triple-negative breast cancer and the αB-crystallin/VEGF protein–protein interaction

  摘要：

  Oestrogen receptor-negative breast cancer, particularly subtypes such as triple-negative breast cancer (TNBC, around 10-15% of cases), are characterised by poor long-term survival, poor response to therapy and early progression to metastasis. Purine-based compounds represent a privileged scaffold in anticancer drug design, with several clinically approved and experimental agents in clinical development comprising a purine core structure. In this study, a series of new purine-based compounds were synthesised; seven of the new analogues were found to significantly reduce the in vitro viability of TNBC cell lines (MDA-MB-231 and MDA-MB-436) with IC50 values of 50M. In previous work, we have proposed a new concept for targeting angiogenesis driving TNBC progression, by disrupting the protein-protein interaction between the molecular chaperone B-crystallin (CRYAB) and VEGF. Since previous clinical studies applying anti-VEGF therapy to TNBC patients have met with limited success, we were interested to test our most promising purine analogues against CRYAB/VEGF, using a custom-designed cell-based CRYAB/VEGF(165) interaction assay platform. Analogues 4e and 4f significantly reduced the interaction between CRYAB/VEGF(165), and compound 4e (100M) was also found to decrease the levels of soluble VEGF expressed by MDA-MB-231 cells by 40%. In conclusion, these promising early activity profiles warrant further investigation to validate this concept.

  DOI：

  10.1007/s00044-018-2275-9

文献信息

• Synthesis of 9-alkyl and 9-heteroalkyl substituted 2-amino-6-guanidinopurines and their influence on the NO-production in macrophages
  作者：Michal Česnek、Antonín Holý、Milena Masojídková、Zdeněk Zídek

  DOI：10.1016/j.bmc.2005.02.008

  日期：2005.4

  9-Alkyl and 9-heteroalkyl substituted derivatives of the 2-amino-6-guanidinopurine were synthesized by alkylation of 2amino -6-chloropurine and subsequent guanidinolysis. The activity of the thus prepared compounds on murine macrophages was examined. Compounds 4a, 4b, and 4d inhibit the LPS + IFN-gamma-induced NO production in murine macrophages while compound 4h stimulates this production. (c) 2005 Elsevier Ltd. All rights reserved.
• Design and synthesis of a new generation of substituted purine hydroxamate analogs as histone deacetylase inhibitors
  作者：Renshuai Liu、Junhua Wang、Weiping Tang、Hao Fang

  DOI：10.1016/j.bmc.2016.02.005

  日期：2016.4

  Histone deacetylase inhibitors have been proved to be great potential for the treatment of cancer. Recently, we designed and modified a series of substituted purine hydroxamate analogs as potent HDAC inhibitors based on our previous studies. The target compounds were investigated for their in vitro HDAC inhibitory activities and anti-proliferative activities. Results indicated that these compounds

  组蛋白脱乙酰基酶抑制剂已被证明在治疗癌症方面具有巨大潜力。最近，我们根据先前的研究设计并修饰了一系列取代的嘌呤异羟肟酸酯类似物，作为有效的HDAC抑制剂。研究了目标化合物的体外HDAC抑制活性和抗增殖活性。结果表明，这些化合物可有效抑制HDAC，对肿瘤细胞具有明显的抗增殖活性。可能地，目标化合物4m和4n在酶抑制活性和细胞抗增殖活性测定方面均优于SAHA。
• The discovery of purine-based agents targeting triple-negative breast cancer and the αB-crystallin/VEGF protein–protein interaction
  作者：Nelly A. Fosu-Mensah、Wen Jiang、Andrea Brancale、Jun Cai、Andrew D. Westwell

  DOI：10.1007/s00044-018-2275-9

  日期：2019.2

  Oestrogen receptor-negative breast cancer, particularly subtypes such as triple-negative breast cancer (TNBC, around 10-15% of cases), are characterised by poor long-term survival, poor response to therapy and early progression to metastasis. Purine-based compounds represent a privileged scaffold in anticancer drug design, with several clinically approved and experimental agents in clinical development comprising a purine core structure. In this study, a series of new purine-based compounds were synthesised; seven of the new analogues were found to significantly reduce the in vitro viability of TNBC cell lines (MDA-MB-231 and MDA-MB-436) with IC50 values of 50M. In previous work, we have proposed a new concept for targeting angiogenesis driving TNBC progression, by disrupting the protein-protein interaction between the molecular chaperone B-crystallin (CRYAB) and VEGF. Since previous clinical studies applying anti-VEGF therapy to TNBC patients have met with limited success, we were interested to test our most promising purine analogues against CRYAB/VEGF, using a custom-designed cell-based CRYAB/VEGF(165) interaction assay platform. Analogues 4e and 4f significantly reduced the interaction between CRYAB/VEGF(165), and compound 4e (100M) was also found to decrease the levels of soluble VEGF expressed by MDA-MB-231 cells by 40%. In conclusion, these promising early activity profiles warrant further investigation to validate this concept.