ethyl 4-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)butanoate | 75058-89-8

• 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: ethyl 4-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)butanoate
• 英文别名: ethyl 4-(1,3-dimethyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-7-yl)butanoate；Theophylline-(7)-butyric acid ethyl ester；Ethyl 4-(1,3-dimethyl-2,6-dioxopurin-7-yl)butanoate
• CAS: 75058-89-8
• 化学式: C₁₃H₁₈N₄O₄
• 分子量: 294.31
• InChiKey: KIBWFDKAGZXFSH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  21
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  84.7
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ethyl 4-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)butanoate 在 盐酸 、 hydrazine hydrate 作用下， 以 甲醇 、 乙醇 为溶剂， 反应 98.0h， 生成 4-(8-ethoxy-1,3-dimethyl-2,6-dioxo-2,3,6,7-tetrahydro-1H-purin-7-yl)-N'-(2-hydroxy-4-methoxybenzylidene)butanehydrazide
  参考文献：
  名称：

  新型嘌呤-2,6-二酮丁酰肼衍生物作为具有潜在抗炎活性的双重PDE4 / 7抑制剂：设计，合成和生物学评估。

  摘要：

  合成了一种新的基于配体的方法设计的嘌呤-2,6-二酮丁酰肼衍生物，并评估了它们对PDE4B和PDE7A同工酶的体外活性。7,8-二取代嘌呤-2,6-二酮衍生物31、34、37和40似乎是最有效的PDE4 / 7抑制剂，IC50值分别在参考咯利普兰和BRL-50481范围内。 。此外，对接研究解释了嘌呤-2,6-二酮核的7位上的N-（2,3,4-三羟基亚苄基）丁酰肼取代基对于双重PDE4 / 7抑制特性的重要性。两种cAMP特异性PDE同工酶的抑制作用均会产生强大的抗TNF-α作用。在体内研究中，LPS诱导的内毒素血症大鼠体内的化合物31、34和37使该促炎细胞因子的最大浓度降低了53，

  DOI：

  10.1016/j.ejmech.2018.01.068
• 作为产物：
  描述：

  4-溴丁酸乙酯 、 8-溴茶碱 在 苄基三乙基氯化铵 、 potassium carbonate 作用下， 以 丙酮 为溶剂， 生成 ethyl 4-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)butanoate
  参考文献：
  名称：

  Novel phosphodiesterases inhibitors from the group of purine-2,6-dione derivatives as potent modulators of airway smooth muscle cell remodelling

  摘要：

  Airway remodelling (AR) is an important pathological feature of chronic asthma and chronic obstructive pulmonary disease. The etiology of AR is complex and involves both lung structural and immune cells. One of the main contributors to airway remodelling is the airway smooth muscle (ASM), which is thickened by asthma, becomes more contractile and produces more extracellular matrix. As a second messenger, adenosine 3',5'-cyclic monophosphate (cAMP) has been shown to contribute to ASM cell (ASMC) relaxation as well as to anti-remodelling effects in ASMC. Phosphodiesterase (PDE) inhibitors have drawn attention as an interesting new group of potential anti-inflammatory and anti-remodelling drugs. Recently, new hydrazide and amide purine-2,6-dione derivatives with anti-inflammatory properties have been synthesized by our team (compounds 1 and 2). We expanded our study of their PDE selectivity profile, ability to increase intracellular cAMP levels, metabolic stability and, above all, their capacity to modulate cell responses associated with ASMC remodelling. The results show that both compounds have subtype specificity for several PDE isoforms (including inhibition of PDE1, PDE3, PDE4 and PDE7). Interestingly, such combined PDE subtype inhibition exerts improved anti-remodelling efficacies against several ASMC-induced responses such as proliferation, contractility, extracellular matrix (ECM) protein expression and migration when compared to other non-selective and selective PDE inhibitors. Our findings open novel perspectives in the search for new chemical entities with dual anti-inflammatory and anti-remodelling profiles in the group of purine-2,6-dione derivatives as broad-spectrum PDE inhibitors.

  DOI：

  10.1016/j.ejphar.2019.172779

文献信息

• Antigen, antiserum and immunoassay for theophylline
  申请人：Byk Gulden Lomberg Chemische Fabrik GmbH

  公开号：US04302438A1

  公开（公告）日：1981-11-24

  By injecting a host animal with a member of a particular group of antigens [a theophylline-(7)-alkanecarboxylic acid covalently bonded to an immunogenic carrier (IGC) via the carboxyl group], antibodies, advantageously employed in determining small amounts of theophylline in biological liquids by immunoassay methods, are obtained.

  通过将特定抗原组的成员（茶碱-（7）-烷基羧酸通过羧基与免疫原载体（IGC）共价键合）注射到宿主动物中，可以获得抗体。这些抗体可以优势地用于通过免疫测定方法测定生物液中微量茶碱。
• Purine Diones As Wnt Pathway Modulators
  申请人：AGENCY FOR SCIENCE, TECHNOLOGY AND RESEARCH

  公开号：US20160090386A1

  公开（公告）日：2016-03-31

  The invention relates to the use of compounds of general structure (I) in modulation of the Wnt pathway [Formula should be inserted here] wherein R 1 , R 2 , R 3 , R 4 and R 5 are each, independently, H or an alkyl group; D is selected from the group consisting of H, halogen, alkyl, cycloalkyl, aryl, and dialkylamino, each (other than H and halogen) being optionally substituted; Ar is an aryl or heteroaryl group, optionally substituted; Cy is an aryl, heteroaryl or a saturated ring containing at least one heteroatom, each being optionally substituted; and n is an integer from 1 to 3.

  本发明涉及一般结构（I）化合物在调节Wnt途径中的使用[应在此处插入公式]其中R1、R2、R3、R4和R5各自独立地为H或烷基；D从H、卤素、烷基、环烷基、芳基和二烷基氨基等中选择，除H和卤素外，每种选择都可以被选择性地取代；Ar是芳基或杂芳基，可以被选择性地取代；Cy是芳基、杂芳基或至少含有一个杂原子的饱和环，每个都可以被选择性地取代；n是1到3的整数。
• Purine diones as Wnt pathway modulators
  申请人：Agency for Science, Technology and Research

  公开号：US10472360B2

  公开（公告）日：2019-11-12

  The invention relates to the use of compounds of general structure (I) in modulation of the Wnt pathway [Formula should be inserted here] wherein R1, R2, R3, R4 and R5 are each, independently, H or an alkyl group; D is selected from the group consisting of H, halogen, alkyl, cycloalkyl, aryl, and dialkylamino, each (other than H and halogen) being optionally substituted; Ar is an aryl or heteroaryl group, optionally substituted; Cy is an aryl, heteroaryl or a saturated ring containing at least one heteroatom, each being optionally substituted; and n is an integer from 1 to 3.

  本发明涉及一般结构(I)化合物在调节 Wnt 通路中的用途[此处应插入式子] 其中 R1、R2、R3、R4 和 R5 各自独立地为 H 或烷基； D 选自 H、卤素、烷基、环烷基、芳基和二烷基氨基组成的组，每种基团（H 和卤素除外）均被任选取代；Ar 是芳基或杂芳基，任选被取代；Cy 是芳基、杂芳基或含有至少一个杂原子的饱和环，每种基团均被任选取代；以及 n 是 1 至 3 的整数。
• 1H NMR study of the complexation of aromatic drugs with dimethylxanthine derivatives
  作者：A.A. Hernandez Santiago、M. Gonzalez Flores、S.A. Rosas Castilla、A.M. Cervantes Tavera、R. Gutierrez Perez、V.V. Khomich、D.V. Ovchinnikov、H.G. Parkes、M.P. Evstigneev

  DOI：10.1016/j.molstruc.2011.11.045

  日期：2012.2

  With an aim of searching efficient interceptors of aromatic drugs, the self- and hetero-association of dimethylxanthine derivatives with different structures, selected according to Strategy 1 (variation of the position of methyl groups) and Strategy 2 (variation of the length of -(CH2)(n)-COOH group), with aromatic drug molecules: Ethidium Bromide, Proflavine and Daunomycin, were studied using H-1 NMR spectroscopy. It was found that the association proceeds in a form of stacking-type complexation and its energetics is relatively independent on the structure of the dimethylxanthines. However, on average, the dimethylxanthines possess higher hetero-association constant and, hence, higher interceptor ability as compared to the trimethylxanthine, Caffeine, used during the past two decades as a typical interceptor molecule. (C) 2011 Elsevier B.V. All rights reserved.
• PURINE DIONES AS WNT PATHWAY MODULATORS
  申请人：Agency for Science, Technology and Research

  公开号：EP2999699A1

  公开（公告）日：2016-03-30