9-butyl-2,6-dichloro-9H-purine | 502184-58-9

• 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: 9-butyl-2,6-dichloro-9H-purine
• 英文别名: 9-Butyl-2,6-dichloropurine
• CAS: 502184-58-9
• 化学式: C₉H₁₀Cl₂N₄
• 分子量: 245.111
• InChiKey: QCONULTUOXUVBX-UHFFFAOYSA-N

物化性质

• 熔点：
  45-47 °C
• 沸点：
  313.2±52.0 °C(Predicted)
• 密度：
  1.50±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 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：

  9-butyl-2,6-dichloro-9H-purine 在 palladium on activated charcoal sodium azide 、 氢气 作用下， 以 乙醇 、 水 为溶剂， 反应 2.0h， 以86%的产率得到9-butyl-9H-purine-2,6-diamine
  参考文献：
  名称：

  Mitsunobu Coupling of Nucleobases and Alcohols:  An Efficient, Practical Synthesis for Novel Nonsugar Carbon Nucleosides

  摘要：

  A simple facile synthesis of substituted purine derivatives has been developed by using Mitsunobu conditions for an alcohol and a respective nucleobase. A wide range of alcohols produces good to excellent yield (> 90%). The resulting purine analogues show good regioselectivity with N-9 substitution as the dominant products in most of the cases. Application of diastereospecific alcohols reveals a complete inversion of the carbon stereogenic center giving a single diastereomer. More than two dozen novel nucleobase derivatives have been prepared in high yield.

  DOI：

  10.1021/jo070515+
• 作为产物：
  描述：

  2,6-二氯嘌呤 、 正丁醇 在 偶氮二甲酸二异丙酯 、 三苯基膦 作用下， 以 四氢呋喃 为溶剂， 以86%的产率得到9-butyl-2,6-dichloro-9H-purine
  参考文献：
  名称：

  Trisubstituted purine inhibitors of PDGFRα and their antileukemic activity in the human eosinophilic cell line EOL-1

  摘要：

  Inhibition of protein kinases is a validated concept for pharmacological intervention in cancers. Many kinase inhibitors have been approved for clinical use, but their practical application is often limited. Here, we describe a collection of 23 novel 2,6,9-trisubstituted purine derivatives with nanomolar inhibitory activities against PDGFR alpha, a receptor tyrosine kinase often found constitutively activated in various tumours. The compounds demonstrated strong and selective cytotoxicity in the human eosinophilic leukemia cell line EOL-1, whereas several other cell lines were substantially less sensitive. The cytotoxicity in EOL-1, which is known to express the FIP1L1-PDGFR alpha fusion gene encoding an oncogenic kinase, correlated significantly with PDGFR alpha inhibition. EOL-1 cells treated with the compounds also exhibited dose-dependent inhibition of PDGFR alpha autophosphorylation and suppression of its downstream signaling pathways with concomitant G1 phase arrest, confirming the proposed mechanism of action. Our results show that substituted purines can be used as platforms for preparing tyrosine kinase inhibitors with specific activity towards eosinophilic leukemia. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2017.10.032

文献信息

• 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。
• Synthesis and Pharmacophore Modelling of 2,6,9-Trisubstituted Purine Derivatives and Their Potential Role as Apoptosis-Inducing Agents in Cancer Cell Lines
  作者：Jeannette Calderón-Arancibia、Christian Espinosa-Bustos、Álvaro Cañete-Molina、Ricardo Tapia、Mario Faúndez、Maria Torres、Adam Aguirre、Margot Paulino、Cristian Salas

  DOI：10.3390/molecules20046808

  日期：——

  A series of 2,6,9-trisubstituted purine derivatives have been synthesized and investigated for their potential role as antitumor agents. Twelve compounds were obtained by a three step synthetic procedure using microwave irradiation in a pivotal step. All compounds were evaluated in vitro to determine their potential effect on cell toxicity by the MTT method and flow cytometry analysis on four cancer cells lines and Vero cells. Three out of twelve compounds were found to be promising agents compared to a known and effective anticancer drug, etoposide, in three out of four cancer cell lines assayed with considerable selectivity. Preliminary flow cytometry data suggests that compounds mentioned above induce apoptosis on these cells. The main structural requirements for their activity for each cancer cell line were characterized with a preliminary pharmacophore model, which identified aromatic centers, hydrogen acceptor/donor center and a hydrophobic area. These features were consistent with the cytotoxic activity of the assayed compounds.

  合成并研究了一系列2,6,9-三取代嘌呤衍生物，以探讨其作为抗肿瘤剂的潜在作用。通过三步合成程序获得了十二个化合物，其中微波辐射在一个关键步骤中发挥了重要作用。所有化合物都进行了体外评估，以确定其对细胞毒性的潜在影响，使用MTT法和流式细胞术分析四种癌细胞系和Vero细胞。与已知的有效抗癌药物依托泊苷相比，十二个化合物中有三个在四种癌细胞系中显示出良好的选择性，具有潜在的应用前景。初步的流式细胞术数据显示，上述化合物能诱导这些细胞的凋亡。每种癌细胞系的活性主要结构要求通过初步药效团模型进行了表征，该模型确定了芳香中心、氢受体/供体中心和疏水区域。这些特征与所测试化合物的细胞毒性活性一致。
• Discovery of novel 9H-purin derivatives as dual inhibitors of HDAC1 and CDK2
  作者：Yu Yu、Dongzhi Ran、Junhao Jiang、Tao Pan、Yanrong Dan、Qiang Tang、Wei Li、Lin Zhang、LinLing Gan、Zongjie Gan

  DOI：10.1016/j.bmcl.2019.06.059

  日期：2019.8

  HDAC and CDK inhibitors have been demonstrated to be synergistically in suppressing cancer cell proliferation and inducing apoptosis. In this work, we incorporated the pharmacophore groups of HDACs and CDKs inhibitors into one molecule to design and synthesize a series of purin derivatives as HDAC/CDK dual inhibitors. The lead compound 6d, showing good HDAC1 and CDK2 inhibitory activity with IC50 values

  HDAC和CDK抑制剂已被证明在抑制癌细胞增殖和诱导细胞凋亡方面具有协同作用。在这项工作中，我们将HDACs和CDKs抑制剂的药效基团整合到一个分子中，以设计和合成一系列作为HDAC / CDK双重抑制剂的嘌呤衍生物。铅化合物6d表现出良好的HDAC1和CDK2抑制活性，IC 50值分别为5.8和56 nM，在体外对几种癌细胞表现出诱人的效力。这项工作可能会导致发现新型支架和潜在的双重HDAC / CDK抑制剂。
• Synthesis of Novel C6-Phosphonated Purine Nucleosides under Microwave Irradiation by SNAr−Arbuzov Reaction
  作者：Gui-Rong Qu、Ran Xia、Xi-Ning Yang、Jian-Guo Li、Dong-Chao Wang、Hai-Ming Guo

  DOI：10.1021/jo702680p

  日期：2008.3.1

  Novel C6-phosphonated purine nucleosides were obtained in good to excellent isolated yields by the simple and catalyst-free SNAr−Arbuzov reaction of trialkyl phosphite with 6-choloropurine nucleosides, including a series of nonsugar carbon nucleosides. Shorter reaction times were needed, and substantially higher yields were obtained under microwave irradiation conditions compared with conventional

  通过亚磷酸三烷基酯与6-胆嘌呤核苷的简单且无催化剂的SNAr-Arbuzov反应，包括一系列非糖碳核苷，可以很好地分离出高产的新型C6-膦化嘌呤核苷。与常规加热条件相比，需要更短的反应时间，并且在微波辐射条件下获得了实质上更高的产率。
• Straightforward and Highly Efficient Catalyst-Free One-Step Synthesis of 2-(Purin-6-yl)acetoacetic Acid Ethyl Esters, (Purin-6-yl)acetates, and 6-Methylpurines through S_NAr-Based Reactions of 6-Halopurines with Ethyl Acetoacetate
  作者：Gui-Rong Qu、Zhi-Jie Mao、Hong-Ying Niu、Dong-Chao Wang、Chao Xia、Hai-Ming Guo

  DOI：10.1021/ol9002256

  日期：2009.4.16

  synthesis of purines bearing functionalized carbon substituents or methyl in position 6 was developed. Under different reaction conditions, 6-halopurine derivatives could react with ethyl acetoacetate efficiently to yield 2-(purin-6-yl)acetoacetic acid ethyl esters, (purin-6-yl)acetates and 6-methylpurines respectively. No metal catalyst and ligand were required.

  开发了一种新颖的合成嘌呤的新方法，该嘌呤在6位带有官能化的碳取代基或甲基。在不同的反应条件下，6-卤代嘌呤衍生物可与乙酰乙酸乙酯有效反应，分别生成2-（嘌呤-6-基）乙酰乙酸乙酯，（嘌呤-6-基）乙酸酯和6-甲基嘌呤。不需要金属催化剂和配体。