8-chloro-1,3-dimethyl-7-(4-chlorobenzyl)-3,7-dihydropurine-2,6-dione  | 1604-78-0

• 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: 8-chloro-1,3-dimethyl-7-(4-chlorobenzyl)-3,7-dihydropurine-2,6-dione
• 英文别名: 8-chloro-7-(4-chlorobenzyl)-1,3-dimethyl-1H-purine-2,6(3H,7H)-dione；8-chloro-7-(4-chloro-benzyl)-1,3-dimethyl-3,7-dihydro-purine-2,6-dione；7-p-Chlorbenzyl-8-chlor-theophyllin；8-chloro-7-[(4-chlorophenyl)methyl]-1,3-dimethylpurine-2,6-dione
• CAS: 1604-78-0
• 化学式: C₁₄H₁₂Cl₂N₄O₂
• mdl: MFCD01556405
• 分子量: 339.181
• InChiKey: QXFUIEDAJJGUJX-UHFFFAOYSA-N

物化性质

• 沸点：
  550.8±60.0 °C(Predicted)
• 密度：
  1.53±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  58.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  8-chloro-1,3-dimethyl-7-(4-chlorobenzyl)-3,7-dihydropurine-2,6-dione  在 一水合肼 作用下， 以86%的产率得到8-hydrazino-1,3-dimethyl-7-(4-chlorobenzyl)-3,7-dihydropurine-2,6-dione
  参考文献：
  名称：

  Design and synthesis of EGFR dimerization inhibitors and evaluation of their potential in the treatment of psoriasis

  摘要：

  Hit compounds from in silico screening for inhibitors of the EGFR dimerization process were evaluated for their anti-proliferative (CCD-1106 keratinocytes) and anti-oxidant (TBA assay) activity and their effect on EGFR dimerization (BS3 chemical crosslinking assay). 7-Benzyl-8-{N'-[1-( 3-ethoxy-4-hydroxyphenyl)meth-(Z)-ylidene]hydrazino}-1,3-dimethylxanthine 2a (127 mu M) leads to 37% inhibition of p-EGFR dimerization in the CCD-1106 cell line and also inhibits phosphorylation of proteins in the MAPK/ERK pathway, ERK 1/2 and p-38. Based on this initial data, 2a was selected for further study and was evaluated for its anti-proliferative activity in a range of keratinocyte (CCD-1106, HaCaT and NHEK) and monocyte (ThP1 and U937) cell lines. Xanthine 2a is pro-apoptotic in HaCaT keratinocytes, as shown by electron microscopy, caspase 3/7, and annexin V-FITC/PI flow cytometric assays. It is significantly less cytotoxic than the established antipsoriatic agent dithranol 14, as determined by MTT and LDH release assays, and thus has potential as a lead compound for the treatment of psoriasis. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.07.048
• 作为产物：
  描述：

  8-氯茶碱 、 4-氯苄溴 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以95%的产率得到8-chloro-1,3-dimethyl-7-(4-chlorobenzyl)-3,7-dihydropurine-2,6-dione 
  参考文献：
  名称：

  Design and synthesis of EGFR dimerization inhibitors and evaluation of their potential in the treatment of psoriasis

  摘要：

  Hit compounds from in silico screening for inhibitors of the EGFR dimerization process were evaluated for their anti-proliferative (CCD-1106 keratinocytes) and anti-oxidant (TBA assay) activity and their effect on EGFR dimerization (BS3 chemical crosslinking assay). 7-Benzyl-8-{N'-[1-( 3-ethoxy-4-hydroxyphenyl)meth-(Z)-ylidene]hydrazino}-1,3-dimethylxanthine 2a (127 mu M) leads to 37% inhibition of p-EGFR dimerization in the CCD-1106 cell line and also inhibits phosphorylation of proteins in the MAPK/ERK pathway, ERK 1/2 and p-38. Based on this initial data, 2a was selected for further study and was evaluated for its anti-proliferative activity in a range of keratinocyte (CCD-1106, HaCaT and NHEK) and monocyte (ThP1 and U937) cell lines. Xanthine 2a is pro-apoptotic in HaCaT keratinocytes, as shown by electron microscopy, caspase 3/7, and annexin V-FITC/PI flow cytometric assays. It is significantly less cytotoxic than the established antipsoriatic agent dithranol 14, as determined by MTT and LDH release assays, and thus has potential as a lead compound for the treatment of psoriasis. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.07.048

文献信息

• SUBSTITUTED XANTHINES AND METHODS OF USE THEREOF
  申请人：Hydra Biosciences, Inc.

  公开号：US20160145257A1

  公开（公告）日：2016-05-26

  Compounds, compositions and methods are described for inhibiting the TRPC5 ion channel and disorders related to TRPC5.

  本文描述了抑制TRPC5离子通道及与TRPC5相关的疾病的化合物、组合物和方法。
• US2014/275528
  申请人：——

  公开号：——

  公开（公告）日：——
• US20140275528A1
  申请人：——

  公开号：——

  公开（公告）日：——
• [EN] SUBSTITUTED XANTHINES AND METHODS OF USE THEREOF<br/>[FR] XANTHINES SUBSTITUÉES ET LEURS PROCÉDÉS D'UTILISATION
  申请人：HYDRA BIOSCIENCES INC

  公开号：WO2014152287A2

  公开（公告）日：2014-09-25

  Compounds, compositions and methods are described for inhibiting the TRPC5 ion channel and disorders related to TRPC5.
• Design and synthesis of EGFR dimerization inhibitors and evaluation of their potential in the treatment of psoriasis
  作者：Donna Petch、Rosaleen J. Anderson、Anne Cunningham、Suja E. George、David E. Hibbs、Ran Liu、Simon P. Mackay、Andrew Paul、David A.P. Small、Paul W. Groundwater

  DOI：10.1016/j.bmc.2012.07.048

  日期：2012.10

  Hit compounds from in silico screening for inhibitors of the EGFR dimerization process were evaluated for their anti-proliferative (CCD-1106 keratinocytes) and anti-oxidant (TBA assay) activity and their effect on EGFR dimerization (BS3 chemical crosslinking assay). 7-Benzyl-8-N'-[1-( 3-ethoxy-4-hydroxyphenyl)meth-(Z)-ylidene]hydrazino}-1,3-dimethylxanthine 2a (127 mu M) leads to 37% inhibition of p-EGFR dimerization in the CCD-1106 cell line and also inhibits phosphorylation of proteins in the MAPK/ERK pathway, ERK 1/2 and p-38. Based on this initial data, 2a was selected for further study and was evaluated for its anti-proliferative activity in a range of keratinocyte (CCD-1106, HaCaT and NHEK) and monocyte (ThP1 and U937) cell lines. Xanthine 2a is pro-apoptotic in HaCaT keratinocytes, as shown by electron microscopy, caspase 3/7, and annexin V-FITC/PI flow cytometric assays. It is significantly less cytotoxic than the established antipsoriatic agent dithranol 14, as determined by MTT and LDH release assays, and thus has potential as a lead compound for the treatment of psoriasis. (C) 2012 Elsevier Ltd. All rights reserved.