6-chloro-9-(2,6-dichlorobenzyl)purine | 70091-24-6

• 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: 6-chloro-9-(2,6-dichlorobenzyl)purine
• 英文别名: 6-chloro-9-[(2,6-dichlorophenyl)methyl]purine
• CAS: 70091-24-6
• 化学式: C₁₂H₇Cl₃N₄
• 分子量: 313.573
• InChiKey: OODRAFIESPIMIC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.08
• 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-chloro-9-(2,6-dichlorobenzyl)purine 在 sodium hydroxide 、 四丁基溴化铵 作用下， 以 乙醇 、 苯 为溶剂， 反应 6.0h， 生成 N-benzyl-N,9-bis(2,6-dichlorobenzyl)adenine
  参考文献：
  名称：

  Ramzaeva, N. P.; Gol'dberg, Yu. Sh.; Alksnis, E. R., Journal of Organic Chemistry USSR (English Translation), 1989, vol. 25, # 8.2, p. 1611 - 1615

  摘要：

  DOI：
• 作为产物：
  描述：

  2,6-二氯氯苄 、 6-氯嘌呤 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 反应 3.0h， 以36%的产率得到6-chloro-9-(2,6-dichlorobenzyl)purine
  参考文献：
  名称：

  取代嘌呤作为高亲和力组胺 H3 受体配体

  摘要：

  继续我们的计划以获得新的组胺 H 3受体 (H 3 R) 配体，在这项工作中，我们介绍了一系列八种新的可合成嘌呤衍生物的合成、H 3 R 亲和力和计算机模拟研究。这些化合物是根据我们之前的配体吡咯并 [2,3- d ] 嘧啶环中呈现的支架被嘌呤核心等排替代而设计的。该设计还考虑在 C-4 处保留双哌啶片段，在 N-9 处保留带有吸电子基团的芳香环，因为这些片段是拟议药效团的一部分。体外筛选结果表明，两种嘌呤衍生物3d和3h对 H 具有高亲和力3 R（Ki 值分别为 2.91 和 5.51 nM）。这两种化合物都比参考药物 pitolisant (K i 6.09 nM) 更有效，并且在体外模型中表现出低毒性（在 HEK-293、SH-SY5Y 和 HepG2 细胞系上， IC 50 > 30 µM）。随后，使用 H 3 R 模型通过对接和分子动力学研究获得这些配体的结合模式，从而确定嘌呤环在增强亲和力方面的重要性，因为

  DOI：

  10.3390/ph15050573

文献信息

• Purine derivatives
  申请人：Takeda Chemical Industries, Ltd.

  公开号：US04189485A1

  公开（公告）日：1980-02-19

  Novel purine derivatives of the formula: ##STR1## wherein R.sup.1 is hydrogen or alkyl of 1 to 3 carbon atoms, R.sup.2 is alkyl of 1 to 3 carbon atoms or allyl, and R.sup.3 and R.sup.4, respectively, mean halogen, and their acid addition salts are provided. These compounds have anticoccidial activity and are useful for treating caecal and/or intestinal coccidiosis in poultry and domestic animals.

  新的嘌呤衍生物的化学式为：##STR1##其中R.sup.1为氢或1至3个碳原子的烷基，R.sup.2为1至3个碳原子的烷基或烯丙基，R.sup.3和R.sup.4分别表示卤素，提供它们的酸盐。这些化合物具有抗球虫活性，可用于治疗家禽和家畜的盲肠和/或肠球虫病。
• Synthesis and evaluation of anticonvulsant and antidepressant activities of 7-alkyl-7H-tetrazolo[1,5-g]purine derivatives
  作者：Shi-Ben Wang、Xian-Qing Deng、Da-Chuan Liu、Hong-Jian Zhang、Zhe-Shan Quan

  DOI：10.1007/s00044-014-1030-0

  日期：2014.10

  Seventeen 7-alkyl-7H-tetrazolo[1,5-g]purine derivatives were synthesized, and their anticonvulsant and antidepressant activities were evaluated in a mouse model. The anticonvulsant effect and neurotoxicity of the compounds were evaluated with a maximal electroshock test and a rotated test in mice, respectively. Most of the compounds had anticonvulsant activity; among the compounds studied, 7-(3-chlorobenzyl)-7H-tetrazolo[1,5-g]purine (3h) was found to be the most potent compound with a median effective dose (ED50) value of 28.9 mg/kg and a protective index value of 15.8, possessing better anticonvulsant activity and higher safety than the marketed drug carbamazepine. To explain the possible mechanism of anticonvulsant activity, compound 3h was tested in pentylenetetrazole-induced seizures tests, and the results suggest that compound 3h exerts anticonvulsant activity through a GABA-mediated mechanism. Forced swimming test showed that at a dose of 40 mg/kg, five compounds have significant antidepressant activity, the most active compound was 7-(2-chlorobenzyl)-7H-tetrazolo[1,5-g]purine (3g), which decreased immobility time by 56 %.
• Ramzaeva, N. P.; Gol'dberg, Yu. Sh.; Lidak, M. Yu., Journal of Organic Chemistry USSR (English Translation), 1989, vol. 25, # 8.2, p. 1608 - 1611
  作者：Ramzaeva, N. P.、Gol'dberg, Yu. Sh.、Lidak, M. Yu.、Alksnis, E. R.、Yure, M. V.、Gudrinietse, E. Ya.

  DOI：——

  日期：——
• Synthesis, Biological Activity, and SAR of Antimycobacterial 9-Aryl-, 9-Arylsulfonyl-, and 9-Benzyl-6-(2-furyl)purines
  作者：Anne Kristin Bakkestuen、Lise-Lotte Gundersen、Bibigul T. Utenova

  DOI：10.1021/jm0408924

  日期：2005.4.1

  9-Aryl-, 9-arylsulfonyl- and 9-benzyl-6-(2-furyl)purines were synthesized by N-alkylation or N-arylation of the purine followed by Stille coupling to introduce the faryl substituent in the 6-position and the compounds screened for activity against Mycobacterium tuberculosis. The 9-aryl- and 9-sulfonylarylpurines exhibited weak activity toward the bacteria, but 9-benzylpurines were good inhibitors especially those carrying electron-donating substituents on the phenyl ring. A chlorine atom in the purine 2-position further enhanced activity. The high antimycobacterial activity (MIC 0.39,mu g/mL against M. tuberculosis), low toxicity against mammalian cells and activity inside macrophages found for 2-chloro-6-(2-furyl)-9-(4-methoxyphenylmethyl)9H-purine makes this compound a highly interesting potential antituberculosis drug.
• ——
  作者：E. Alksnis、D. Korneeva、E. Lukevics

  DOI：10.1023/a:1011973514672

  日期：——