9-(4-chlorophenylmethyl)-2,6-dichloro-9H-purine | 115204-72-3

• 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-(4-chlorophenylmethyl)-2,6-dichloro-9H-purine
• 英文别名: 2,6-dichloro-9-(4-chlorobenzyl)-9H-purine；2,6-Dichloro-9-[(4-chlorophenyl)methyl]-9H-purine；2,6-dichloro-9-[(4-chlorophenyl)methyl]purine
• CAS: 115204-72-3
• 化学式: C₁₂H₇Cl₃N₄
• 分子量: 313.573
• InChiKey: IIURLOMFGCXJOV-UHFFFAOYSA-N

物化性质

• 熔点：
  162-164 °C
• 沸点：
  456.5±55.0 °C(Predicted)
• 密度：
  1.62±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 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：

  2-(三丁基锡烷基)呋喃 、 9-(4-chlorophenylmethyl)-2,6-dichloro-9H-purine 在 tris(dibenzylideneacetone)dipalladium(0) chloroform complex 、 三(2-呋喃基)膦 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 8.0h， 生成 2-chloro-9-(4-chlorophenylmethyl)-6-(2-furyl)-9h-purine
  参考文献：
  名称：

  Purine compounds

  摘要：

  这项发明提供了一种抗分枝杆菌的6-芳基-9-(m-或p-取代苄基)嘌呤和嘌呤类似化合物。

  公开号：

  US20070203159A1
• 作为产物：
  描述：

  4-氯苄溴 、 2,6-二氯嘌呤 在 potassium carbonate 作用下， 以 二甲基亚砜 为溶剂， 反应 22.0h， 以35%的产率得到9-(4-chlorophenylmethyl)-2,6-dichloro-9H-purine
  参考文献：
  名称：

  9-Benzyl-6-(dimethylamino)-9H-purines with antirhinovirus activity

  摘要：

  A series of 9-benzyl-6-(dimethylamino)-9H-purines and 9-benzyl-2-chloro-6-(dimethylamino)-9H-purines were synthesized and tested in cell culture for activity against rhinovirus type 1B. The 9-benzylpurines that were unsubstituted in the 2-position had weak activity. However, introduction of a 2-chloro substituent resulted in a substantial increase in antiviral activity. One of the most active compounds, 2-chloro-6-(dimethylamino)-9-(4-methylbenzyl)-9H-purine (29), had an IC50 value of 0.08 microM against serotype 1B. Four compounds were tested against 18 other rhinovirus serotypes, but the majority tested were less sensitive than type 1B. The range of serotype sensitivity for 29 varied from 0.08 to 14 microM. These 9-benzyl-2-chloro-9H-purines represent a new class of antiviral agents with in vitro activity against rhinoviruses.

  DOI：

  10.1021/jm00118a025

文献信息

• Substituted Purines as High-Affinity Histamine H3 Receptor Ligands
  作者：Christian Espinosa-Bustos、Luisa Leitzbach、Tito Añazco、María J. Silva、Andrea del Campo、Alejandro Castro-Alvarez、Holger Stark、Cristian O. Salas

  DOI：10.3390/ph15050573

  日期：——

  3d and 3h, elicit high affinities to the H3R (Ki values of 2.91 and 5.51 nM, respectively). Both compounds are more potent than the reference drug pitolisant (Ki 6.09 nM) and show low toxicity with in vitro models (IC50 > 30 µM on HEK-293, SH-SY5Y and HepG2 cell lines). Subsequently, binding modes of these ligands are obtained using a model of H3R by docking and molecular dynamics studies, thus determining

  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
• Synthesis of 8-Bromo-<i>N</i>-benzylpurines via 8-Lithiated Purines: Scope and Limitations
  作者：Thywill Gamadeku、Lise-Lotte Gundersen

  DOI：10.1080/00397910903318708

  日期：2010.8.16

  9-Benzylpurines have been lithiated in the 8-position and subsequently brominated when trapped with BrCCl2CCl2Br. The 8-bromopurines were isolated in excellent yields when the benzyl group carried an alkoxy or alkyl group in the ortho or para position. Without these substituents, the conversion was generally less, and formation of 8,8'-purinyl dimers was observed. There was also evidence of debenzylation in some instances. Bromination of 7-benzylpurines employing the same set of reaction conditions has also been achieved.
• 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.
• KELLEY, JAMES L.;LINN, JAMES A.;KROCHMAL, MARK P.;SELWAY, J. W. T., J. MED. CHEM., 31,(1988) N 10, C. 2001-2004
  作者：KELLEY, JAMES L.、LINN, JAMES A.、KROCHMAL, MARK P.、SELWAY, J. W. T.

  DOI：——

  日期：——