8-氯-1,3-二甲基-7-[(4-硝基苯基)甲基]嘌呤-2,6-二酮 | 1604-79-1

• 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: 8-氯-1,3-二甲基-7-[(4-硝基苯基)甲基]嘌呤-2,6-二酮
• 英文名称: 8-chloro-1,3-dimethyl-7-(4-nitrobenzyl)-3,7-dihydropurine-2,6-dione
• 英文别名: 8-chloro-1,3-dimethyl-7-(4-nitro-benzyl)-3,7-dihydro-purine-2,6-dione；1,3-dimethyl-7-(4-nitro-benzyl)-8-chloro-xanthine；7-p-Nitrobenzyl-8-chlor-theophyllin；8-Chloro-1,3-dimethyl-7-(4-nitrobenzyl)-3,7-dihydro-1H-purine-2,6-dione；8-chloro-1,3-dimethyl-7-[(4-nitrophenyl)methyl]purine-2,6-dione
• CAS: 1604-79-1
• 化学式: C₁₄H₁₂ClN₅O₄
• mdl: MFCD01797372
• 分子量: 349.733
• InChiKey: XKRHRNHJGNHEPT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  24
• 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：
  104
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  8-氯-1,3-二甲基-7-[(4-硝基苯基)甲基]嘌呤-2,6-二酮 在 一水合肼 作用下， 以92%的产率得到8-hydrazino-1,3-dimethyl-7-(4-nitrobenzyl)-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 、 对硝基溴化苄 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以80%的产率得到8-氯-1,3-二甲基-7-[(4-硝基苯基)甲基]嘌呤-2,6-二酮
  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

• Xanthine derivatives, the preparation thereof and their use as pharmaceutical compositions
  申请人：——

  公开号：US20020198205A1

  公开（公告）日：2002-12-26

  The present invention relates to substituted xanthines of general formula 1 wherein R 1 to R 4 are defined as in claim 1, the tautomers and the stereoisomers thereof, mixtures thereof, the prodrugs and the salts thereof which have valuable pharmacological properties, particularly an inhibiting effect on the activity of the enzyme dipeptidylpeptidase-IV (DPP-IV).

  本发明涉及一般式1的取代黄嘌呤，其中R1至R4如权利要求1中定义，其互变异构体和立体异构体，其混合物，其前药和其盐，具有有价值的药理特性，特别是对酶二肽基肽酶-IV（DPP-IV）活性的抑制作用。
• Xanthine derivatives,production and use thereof as medicament
  申请人：——

  公开号：US20040077645A1

  公开（公告）日：2004-04-22

  The present invention relates to substituted xanthines of general formula 1 wherein R 1 to R 4 are defined as in claim 1, the tautomers and the stereoisomers thereof, mixtures thereof, the prodrugs and the salts thereof which have valuable pharmacological properties, particularly an inhibiting effect on the activity of the enzyme dipeptidylpeptidase-IV (DPP-IV).

  本发明涉及一般式1的取代黄嘌呤，其中R1至R4如权利要求1所定义，其互变异构体和立体异构体，混合物，前药和盐具有有价值的药理学性质，特别是对酶二肽基肽酶IV（DPP-IV）的抑制作用。
• XANTHINE DERIVATIVES, THE PREPARATION THEREOF AND THEIR USE AS PHARMACEUTICAL COMPOSITIONS
  申请人：Himmelsbach Frank

  公开号：US20060247226A1

  公开（公告）日：2006-11-02

  The present invention relates to substituted xanthines of general formula wherein R 1 to R 4 are defined as in claim 1, the tautomers and the stereoisomers thereof, mixtures thereof, the prodrugs and the salts thereof which have valuable pharmacological properties, particularly an inhibiting effect on the activity of the enzyme dipeptidylpeptidase-IV (DPP-IV).

  本发明涉及一般式为的取代黄嘌呤，其中R1至R4的定义如权利要求1所述，其互变异构体和立体异构体，混合物，前药和盐具有有价值的药理学性质，特别是对酶二肽基肽酶-IV（DPP-IV）的抑制作用。
• Xanthine derivatives, the preparation thereof and their use as pharmaceutical compositions
  申请人：HIMMELSBACH Frank

  公开号：US20110144095A1

  公开（公告）日：2011-06-16

  The present invention relates to substituted xanthines of general formula wherein R 1 to R 4 are as defined herein, the tautomers and the stereoisomers thereof, mixtures thereof, the prodrugs and the salts thereof which have valuable pharmacological properties, particularly an inhibiting effect on the activity of the enzyme dipeptidylpeptidase-IV (DPP-IV).

  本发明涉及一般式为的取代黄嘌呤，其中R1至R4的定义如本文所述，其互变异构体和立体异构体，混合物，前药和盐具有有价值的药理学特性，特别是对酶二肽基肽酶-IV（DPP-IV）的抑制作用。
• Xanthine Derivatives, the Preparation Thereof and Their Use as Pharmaceutical Compositions
  申请人：HIMMELSBACH Frank

  公开号：US20120035158A1

  公开（公告）日：2012-02-09

  The present invention relates to substituted xanthines of general formula wherein R 1 to R 4 are defined as in claim 1 , the tautomers and the stereoisomers thereof, mixtures thereof, the prodrugs and the salts thereof which have valuable pharmacological properties, particularly an inhibiting effect on the activity of the enzyme dipeptidylpeptidase-IV (DPP-IV).

  本发明涉及一般式为的取代黄嘌呤，其中R1至R4如权利要求1所定义，其互变异构体和立体异构体，其混合物，其前药和其盐具有有价值的药理特性，特别是对酶二肽基肽酶-IV（DPP-IV）活性的抑制作用。