5-{4-[(2-methyl-4-quinolinyl)methoxy]phenyl}-5-(1-piperazinyl)-2,4,6(1H, 3H, 5H)-pyrimidinetrione | 556052-20-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 5-{4-[(2-methyl-4-quinolinyl)methoxy]phenyl}-5-(1-piperazinyl)-2,4,6(1H, 3H, 5H)-pyrimidinetrione
• 英文别名: 5-{4-[(2-methyl-4-quinolinyl)methoxy]phenyl}-5-(1-piperazinyl)-2,4,6(1H,3H,5H)-pyrimidinetrione；5-[4-(2-Methyl-quinolin-4-ylmethoxy)-phenyl]-5-piperazin-1-yl-pyrimidine-2,4,6-trione；5-[4-[(2-methylquinolin-4-yl)methoxy]phenyl]-5-piperazin-1-yl-1,3-diazinane-2,4,6-trione
• CAS: 556052-20-1
• 化学式: C₂₅H₂₅N₅O₄
• 分子量: 459.505
• InChiKey: VIJGBSAWWJKQHY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  34
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  113
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  5-{4-[(2-methyl-4-quinolinyl)methoxy]phenyl}-5-(1-piperazinyl)-2,4,6(1H, 3H, 5H)-pyrimidinetrione 、 甲基磺酰氯 生成 5-{4-[(2-methyl-4-quinolinyl)methoxy]phenyl}-5-[4-(methylsulfonyl)-1-piperazinyl]-2,4,6(1H, 3H, 5H)-pyrimidinetrione
  参考文献：
  名称：

  Non-hydroxamate 5-phenylpyrimidine-2,4,6-trione derivatives as selective inhibitors of tumor necrosis factor-α converting enzyme

  摘要：

  New inhibitors of tumor necrosis factor-a converting enzyme (TACE) were discovered with a pyrimidine-2,4,6-trione in place of the commonly used hydroxamic acid. These non-hydroxamate TACE inhibitors were developed by incorporating a 4-(2methyl-4-quinolinylmethoxy)phenyl group, an optimized TACE selective P1' group. Several leads were identified with IC50 values around 100 nM in a porcine TACE assay and selective over MMP-1, -2, -9, -13, and aggrecanase. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.04.039
• 作为产物：
  描述：

  4-羟基苯乙酸甲酯 在 sodium methylate 、 sodium hydride 、 caesium carbonate 、 三氟乙酸 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 2.0h， 生成 5-{4-[(2-methyl-4-quinolinyl)methoxy]phenyl}-5-(1-piperazinyl)-2,4,6(1H, 3H, 5H)-pyrimidinetrione
  参考文献：
  名称：

  Non-hydroxamate 5-phenylpyrimidine-2,4,6-trione derivatives as selective inhibitors of tumor necrosis factor-α converting enzyme

  摘要：

  New inhibitors of tumor necrosis factor-a converting enzyme (TACE) were discovered with a pyrimidine-2,4,6-trione in place of the commonly used hydroxamic acid. These non-hydroxamate TACE inhibitors were developed by incorporating a 4-(2methyl-4-quinolinylmethoxy)phenyl group, an optimized TACE selective P1' group. Several leads were identified with IC50 values around 100 nM in a porcine TACE assay and selective over MMP-1, -2, -9, -13, and aggrecanase. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.04.039

文献信息

• Indole derivatives
  申请人：Yamasaki Noritsugu

  公开号：US20050171185A1

  公开（公告）日：2005-08-04

  A novel indole derivative or a salt thereof is provided, which is represented by the formula: wherein R 1 represents an aryl lower alkyl group, said aryl group may be substituted with one or more groups selected from the group consisting of a halogen atom, an aryl group, a heterocyclic group, an aryl lower alkyl group, an aryl lower alkenyl group, a halo-lower alkyl group, a lower cycloalkyl-lower alkoxy group, a lower cycloalkoxy-lower alkyl group, an aryl lower alkynyl group, an aryloxy lower alkyl group, an aryl lower alkoxy group, a lower alkylthio group, a lower alkoxy group, and an alkenyl group; and R 2 represents a lower alkyl group, a lower alkenyl group, an aryl group, or a heterocyclic group, each of which may be substituted with a hydrogen atom, a lower alkyl group, a lower alkenyl group, or an aryl group. The compound of the present invention has blood sugar level-depressing activity and PDE5-inhibiting activity, and is useful as medicine.

  本发明提供了一种新的吲哚衍生物或其盐，其表示为以下公式：其中，R1表示芳基低烷基基团，所述芳基基团可以用以下一种或多种基团替代：卤原子、芳基基团、杂环基团、芳基低烷基基团、芳基低烯基基团、卤代低烷基基团、低环烷基低烷氧基团、低环烷氧基低烷基基团、芳基低炔基基团、芳氧基低烷基基团、芳基低烷氧基团、低烷基硫基团、低烷氧基团和烯基基团；R2表示低烷基基团、低烯基基团、芳基基团或杂环基团，每个基团可以用氢原子、低烷基基团、低烯基基团或芳基基团替代。本发明化合物具有降低血糖水平的活性和PDE5抑制活性，并可用作药物。
• INDOLE DERIVATIVES
  申请人：FUJISAWA PHARMACEUTICAL CO., LTD.

  公开号：EP1070705A1

  公开（公告）日：2001-01-24

  Novel indole derivatives represented by formula (I) or salts thereof, wherein R1 is aryl-substituted lower alkyl in which the aryl may be substituted by at least one member selected among halogen atoms, aryls, heterocyclic groups, aryl-substituted lower alkyls, aryl-substituted lower alkenyls, lower haloalkyls, (lower cycloalkyl)-substituted lower alkyloxys, (lower cycloalkyloxy)-substituted lower alkyls, aryl-substituted lower alkynyls, aryloxy-substituted lower alkyls, aryl-substituted lower alkyloxys, lower alkylthios, lower alkyloxys, and alkenyls; and R2 is a lower alkyl, lower alkenyl, aryl, or heterocyclic group optionally substituted by halogeno, lower alkyl, lower alkenyl, or aryl. These compounds have a hypoglycemic activity and a PDE5 inhibitory activity and are useful as a drug.

  低级卤代烷基、（低级环烷基）取代的低级烷氧基、（低级环烷氧基）取代的低级烷基、芳基取代的低级炔基、芳氧基取代的低级烷基、芳基取代的低级烷氧基、低级烷硫基、低级烷氧基和烯基；R2 是可选被卤素、低级烷基、低级烯基或芳基取代的低级烷基、低级烯基、芳基或杂环基团。这些化合物具有降血糖活性和 PDE5 抑制活性，可用作药物。
• US6936620B2
  申请人：——

  公开号：US6936620B2

  公开（公告）日：2005-08-30
• Non-hydroxamate 5-phenylpyrimidine-2,4,6-trione derivatives as selective inhibitors of tumor necrosis factor-α converting enzyme
  作者：James J.-W. Duan、Zhonghui Lu、Zelda R. Wasserman、Rui-Qin Liu、Maryanne B. Covington、Carl P. Decicco

  DOI：10.1016/j.bmcl.2005.04.039

  日期：2005.6

  New inhibitors of tumor necrosis factor-a converting enzyme (TACE) were discovered with a pyrimidine-2,4,6-trione in place of the commonly used hydroxamic acid. These non-hydroxamate TACE inhibitors were developed by incorporating a 4-(2methyl-4-quinolinylmethoxy)phenyl group, an optimized TACE selective P1' group. Several leads were identified with IC50 values around 100 nM in a porcine TACE assay and selective over MMP-1, -2, -9, -13, and aggrecanase. (c) 2005 Elsevier Ltd. All rights reserved.