6-氯-9-环戊基嘌呤 | 5444-81-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 中文名称: 6-氯-9-环戊基嘌呤
• 英文名称: 6-chloro-9-cyclopentyl-9H-purine
• 英文别名: 6-chloro-9-cyclopentylpurine
• CAS: 5444-81-5
• 化学式: C₁₀H₁₁ClN₄
• 分子量: 222.677
• InChiKey: UHTKSLVKLNJYII-UHFFFAOYSA-N

物化性质

• 熔点：
  97 °C
• 沸点：
  392.6±45.0 °C(Predicted)
• 密度：
  1.56±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 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：

  6-氯-9-环戊基嘌呤 在 乙醇 、 氨 作用下， 生成 9-环戊基腺嘌呤
  参考文献：
  名称：

  Synthesis of Potential Anticancer Agents. XII. 9-Alkyl-6-substituted-purines²

  摘要：

  DOI：

  10.1021/ja01535a041
• 作为产物：
  描述：

  溴代环戊烷 、 6-氯嘌呤 在 四丁基氢氧化铵 作用下， 以 水 、 乙腈 为溶剂， 反应 0.5h， 以90%的产率得到6-氯-9-环戊基嘌呤
  参考文献：
  名称：

  微波辐照下嘌呤的区域选择性烷基化反应

  摘要：

  通常在阴离子形成后通过用碱和烷基卤处理进行的嘌呤烷基化是复杂的，并且在最好的情况下，获得了N-烷基化化合物的混合物。嘌呤衍生物可以从N -7 和N -9 的烷基化中获得。在这项工作中，对反应条件进行了优化，以区域选择性地获得N -9 的烷基化产物。已经尝试了不同的碱，氢氧化四丁基铵产生了最好的结果。反应取决于所使用的碱和溶剂的类型，并且在使用微波辐照的帮助下显着改善，这也通过减少副产物的形成而显着减少了反应时间。

  DOI：

  10.1002/jhet.4407

文献信息

• Nickel catalyzed alkylation of N-aromatic heterocycles with Grignard reagents through direct C–H bond functionalization
  作者：Peng-Yang Xin、Hong-Ying Niu、Gui-Rong Qu、Rui-Fang Ding、Hai-Ming Guo

  DOI：10.1039/c2cc32396f

  日期：——

  A novel protocol for nickel-catalyzed direct sp2 C–H bond alkylation of N-aromatic heterocycles has been developed. This new reaction proceeded efficiently at room temperature using a Grignard reagent as the coupling partner. This approach provides new access to a variety of alkylated N-aromatic heterocycles which are potentially of great importance in medicinal chemistry.

  一种新的协议已被开发用于镍催化的N-芳香族杂环直接sp² C–H键烷基化反应。该反应在室温下以格里尼亚试剂作为耦合伙伴高效进行。这种方法为获取各种烷基化的N-芳香族杂环提供了新的途径，这些化合物在药物化学中可能具有重要价值。
• Discovery of 3-(((9H-purin-6-yl)amino)methyl)-4,6-dimethylpyridin-2(1H)-one derivatives as novel tubulin polymerization inhibitors for treatment of cancer
  作者：Qiangsheng Zhang、Xi Hu、Guoquan Wan、Jia Wang、Lu Li、Xiuli Wu、Zhihao Liu、Luoting Yu

  DOI：10.1016/j.ejmech.2019.111728

  日期：2019.12

  A new series of 3-(((9H-purin-6-yl)amino)methyl)-4,6-dimethylpyridin-2(1H)-one derivatives were designed, synthesized and demonstrated to act as tubulin polymerization inhibitors. These new derivatives showed significant antitumor activities, among which SKLB0533 demonstrated to be the most potent compound, with IC50 values ranging from 44.5 to 135.5 nM against seven colorectal carcinoma (CRC) cell

  设计，合成并证明了新的3-（（（9H-嘌呤-6-基）氨基）甲基）-4,6-二甲基吡啶-2（1H）-one衍生物可作为微管蛋白聚合抑制剂。这些新的衍生物显示出显着的抗肿瘤活性，其中SKLB0533被证明是最有效的化合物，针对7种结直肠癌（CRC）细胞系的IC50值为44.5至135.5 nM。值得注意的是，SKLB0533没有表现出对其他潜在靶标的活性，例如420种激酶和EZH2。此外，SKLB0533抑制微管蛋白聚合，使细胞周期停在G2 / M期并诱导CRC细胞凋亡。此外，SKLB0533抑制了HCT116异种移植模型中的肿瘤生长，而没有引起明显的主要器官相关毒性，
• Newly synthesized 6-substituted piperazine/phenyl-9-cyclopentyl containing purine nucleobase analogs act as potent anticancer agents and induce apoptosis <i>via</i> inhibiting Src in hepatocellular carcinoma cells
  作者：Ebru Bilget Guven、Irem Durmaz Sahin、Duygu Altiparmak、Burak Servili、Sebnem Essiz、Rengul Cetin-Atalay、Meral Tuncbilek

  DOI：10.1039/d3md00440f

  日期：——

  Newly synthesized 6-substituted piperazine/phenyl-9-cyclopentyl-containing purine nucleobase analogs were tested for their in vitro anticancer activity against human cancer cells. Compounds 15, 17–24, 49, and 56 with IC50 values less than 10 μM were selected for further examination on an enlarged panel of liver cancer cell lines. Experiments revealed that compound 19 utilizes its high cytotoxic potential

  测试了新合成的 6-取代的含哌嗪/苯基-9-环戊基的嘌呤核碱基类似物对人癌细胞的体外抗癌活性。选择 IC50 值小于 10 μM 的化合物 15、17-24、49 和 56 在扩大的肝癌细胞系面板上进一步检查。实验表明，化合物 19 利用其高细胞毒潜能 （IC50 < 5 μM） 在体外诱导细胞凋亡。化合物 19 的 KINOMEscan 选择性评分 S35 为 0.02，S 10 为 0.01，对间变性淋巴瘤激酶 （ALK） 和布鲁顿酪氨酸激酶 （BTK） 的选择性优于其他激酶。通过分子对接和分子动力学模拟，对与 ALK、BTK 和（包含盘状蛋白结构域的受体 2）DDR2 复合的化合物 19 、 21 、 22 、 23 和 56 进行结构分析了结合位点相互作用和结合亲和力。化合物 19 和 56 与激酶的激活环显示出相似的相互作用，而只有化合物 19 到达活性位点的多个亚位点。细胞周期和信号通路分析显示，化合物
• Visible-Light-Mediated Monoselective Ortho C–H Arylation of 6-Arylpurine Nucleosides with Diazonium Salts
  作者：Lei Liang、Ming-Sheng Xie、Hai-Xia Wang、Hong-Ying Niu、Gui-Rong Qu、Hai-Ming Guo

  DOI：10.1021/acs.joc.7b00659

  日期：2017.6.2

  A combined palladium- and photoredox-catalyzed monoselective arylation of 6-arylpurine nucleosides has been developed by employing purine as a directing group via the photoredox reaction, and many functional groups are well tolerated in this direct C-H arylation condition. Various of functionalized purines (nucleosides) which are potentially of great importance in medicinal chemistry could be obtained under visible light irradiation at room temperature within 4 h.
• N6,9-Disubstituted adenines: potent, selective antagonists at the A1 adenosine receptor
  作者：Robert D. Thompson、Sherrie Secunda、John W. Daly、Ray A. Olsson

  DOI：10.1021/jm00113a029

  日期：1991.9

  N6-Substituted 9-methyladenines are potent antagonists of the activation of A1 adenosine receptors. The present study assessed the effect of N6 and N-9 substituents on the binding of adenines to the A1 and A2 receptors, respectively, of rat brain cortex and striatum and also on the antagonism of the A2 receptor mediated stimulation of the adenylate cyclase of PC12 cells by N-ethyladenosine-5'-uronamide. The potency ranking of 9-substituted adenines varied directly with the hydrophobicity of the substituent: cyclopentyl > phenyl > tetrahydrofuryl > methyl > 2-hydroxyethyl. The 9-substituted adenines showed little selectivity for either receptor and the R enantiomer of N6-(1-phenyl-2-propyl)-9-methyladenine was only 4-fold more potent than the S enantiomer at the A1 receptor. An N6-cyclopentyl substituent increased potency at the A1 receptor and decreased potency at the A2 receptor, resulting in selectivity for the A1 receptor of up to 39-fold. The N6-cyclophenyl group completely overshadowed the effect of the hydrophobicity of the 9-substituent. A 2-chloro substituent did not alter the potency of an N6-substituted 9-methyladenine.