5-biphenyl-4-yl-5-[4-(4-nitro-phenyl)-piperazin-1-yl]pyrimidine-2,4,6-trione

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 5-biphenyl-4-yl-5-[4-(4-nitro-phenyl)-piperazin-1-yl]pyrimidine-2,4,6-trione
• 英文别名: Ro 28-2653；5-[4-(4-Nitrophenyl)piperazin-1-yl]-5-(4-phenylphenyl)-1,3-diazinane-2,4,6-trione
• 化学式: C₂₆H₂₃N₅O₅
• 分子量: 485.499
• InChiKey: NJKTYSXXGARILV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  36
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  128
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  5-biphenyl-4-yl-5-[4-(4-nitro-phenyl)-piperazin-1-yl]pyrimidine-2,4,6-trione 在 palladium 10% on activated carbon 氢气 作用下， 以 乙醇 为溶剂， 50.0 ℃ 、400.01 kPa 条件下， 反应 2.0h， 生成 5-[4-(4-aminophenyl)piperazin-1-yl]-5-[1,1'-biphenyl]-4-ylpyrimidine-2,4,6(1H,3H,5H)-trione
  参考文献：
  名称：

  [EN] 5-(1,1'-BIPHENYL)-4-YL-5-(4-(4-AMINOACYLPHENYL)-PIPERAZIN)-1-YL-PYRIMIDINE-2,4,6-TRIONE DERIVATIVES, AS INHIBITORS OF ZINC METALLONDOPEPTIDASES, THEIR PREPARATION AND USE
  [FR] DERIVES DE 5-(1,1'-BIPHENYL)-4-YL-5-(4-(4-AMINOACYLPHENYL)PIPERAZIN)-1-YL-PYRIMIDINE-2,4,6-TRIONE, COMME INHIBITEURS DE ZINC-METALLOENDOPEPTIDASES, LEUR PREPARATION ET UTILISATION.

  摘要：

  本发明涉及新的嘧啶三酮衍生物，其化学式为(I)，其中R1和R2在说明书中有定义，以及其组成和制备方法。这些化合物在治疗涉及金属蛋白酶的疾病中有用。

  公开号：

  WO2006021533A1
• 作为产物：
  描述：

  4-联苯乙酸 在 N-溴代丁二酰亚胺(NBS) 、 potassium tert-butylate 、 对甲苯磺酸 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 、 异丙醇 为溶剂， 反应 11.77h， 生成 5-biphenyl-4-yl-5-[4-(4-nitro-phenyl)-piperazin-1-yl]pyrimidine-2,4,6-trione
  参考文献：
  名称：

  An Improved Synthesis of the Selective Matrix Metalloproteinase Inhibitor, Ro 28-2653

  摘要：

  An efficient synthesis of Ro 28-2653, a selective matrix metalloproteinase inhibitor, has been developed. The title compound was prepared in four steps and 76% overall yield from 4-biphenylacetic acid. The key, barbituric acid formation step was significantly improved by using 2-propanol and potassium tert-butoxide as the solvent and base, respectively, instead of the typical ethanol and sodium ethoxide combination.

  DOI：

  10.1021/op049965j

文献信息

• Metalloprotein inhibitors containing nitrogen based ligands
  申请人：Cohen Seth M.

  公开号：US20120135959A1

  公开（公告）日：2012-05-31

  Provided herein metalloproteinase inhibitors containing nitrogen or mixed nitrogen/oxygen donating zinc binding groups. Also provided are pharmaceutical compositions containing the compounds and methods of treating preventing or ameliorating the diseases associated with metalloproteinase activity using the compounds and compositions.

  本文提供了含有氮或混合氮/氧供体锌结合基团的金属蛋白酶抑制剂。还提供了含有这些化合物的药物组合物，以及使用这些化合物和组合物治疗、预防或改善与金属蛋白酶活性相关的疾病的方法。
• Combination therapy for the treatment of liver diseases
  申请人：Spada Alfred P.

  公开号：US20080207605A1

  公开（公告）日：2008-08-28

  Provided herein are methods for treatment of a liver disease by administering a combination of a matrix metalloproteinase inhibitor and a caspase inhibitor. Also provided are methods for reducing liver damage associated with a liver disease by administering the MMP and caspase inhibitors described herein. Further provided are methods for lowering an elevated level of liver enzymes.

  本文提供了一种治疗肝病的方法，通过给予基质金属蛋白酶抑制剂和半胱氨酸蛋白酶抑制剂的组合。还提供了一种通过给予本文描述的基质金属蛋白酶和半胱氨酸蛋白酶抑制剂来减少与肝病相关的肝损伤的方法。此外，还提供了一种降低升高的肝酶水平的方法。
• 5-(1,1'Biphenyl)-4-Yl-5-(4-(4-Aminoacylphenyl)-Piperazin)-1-Yl-Pyrimidine-2,4,6,-Trione Derivatives, As Inhibitors Of Zinc Metallondopeptidases, Their Preparation And Use
  申请人：Pirotte Bernard

  公开号：US20080096897A1

  公开（公告）日：2008-04-24

  New Pyrimidinetrione derivatives represented by formula (I), wherein R 1 and R 2 are defined in the description, composition thereof, and methods of preparation are described. The compounds are useful in the treatment of disease involving metalloproteinases.

  本发明涉及新的吡啶二酮衍生物，其化学式为(I)，其中R1和R2在说明中有定义，以及其组合物和制备方法。这些化合物在治疗涉及金属蛋白酶的疾病中具有用途。
• Pharmaceutical compositions of pyrimidine-2,4,6-triones
  申请人：Bartsch Pierre

  公开号：US20070191404A1

  公开（公告）日：2007-08-16

  It was surprisingly found that a-trioxopyrimidine-cyclodextrin-complex formed of a trioxopyrimidine derivative represented by the below-described formula (I) and a water-soluble cyclodextrin (further abbreviated as CD) exhibits enhanced water solubility, excellent stability, and low topical stimulation and is useful as a therapeutic agent. Accordingly, the present invention provides a trioxopyrimidine-cyclodextrin complex formed of a trioxopyrimidine derivative or a salt thereof and a cyclodextrin, preferably α-, β- or γ-cyclodextrin or a water-soluble cyclodextrin derivative (water-soluble being defined as a solubility of at least 0.5 gr/100 ml water at 25° C.), wherein the trioxopyrimidine derivative is represented by formula (I). It was furthermore found that such a trioxopyrimidine complex with cyclodextrin and an adjuvant such as L-lysine or L-arginine show improved water solubility and bioavailability, excellent stability, and low topical stimulation and is useful as a therapeutic agent.

  出人意料地发现，以下式(I)所描述的三氧嘧啶衍生物和水溶性环糊精(以下简称CD)形成的a-三氧嘧啶-环糊精复合物具有增强的水溶性，优异的稳定性和低的局部刺激性，可用作治疗剂。因此，本发明提供了由三氧嘧啶衍生物或其盐和环糊精形成的三氧嘧啶-环糊精复合物，优选α-，β-或γ-环糊精或水溶性环糊精衍生物(水溶性定义为在25℃下至少0.5克/100毫升水的溶解度)，其中三氧嘧啶衍生物由式(I)表示。此外，还发现这样的三氧嘧啶-环糊精复合物与辅料如L-赖氨酸或L-精氨酸一起使用，可显示出改善的水溶性和生物利用度，优异的稳定性和低的局部刺激性，可用作治疗剂。
• Metalloproteinase Inhibitors
  申请人：Eriksson Anders

  公开号：US20080306065A1

  公开（公告）日：2008-12-11

  Compounds of the formula (I) wherein z is SO 2 or SO, useful as metalloproteinase inhibitors, especially as inhibitors of MMP12.

  公式为（I）的化合物，其中z为SO2或SO，可用作金属蛋白酶抑制剂，特别是作为MMP12的抑制剂。