5-methyl-5-((2E)-3-{4-[(2-methyl-4-quinolinyl)methoxy]phenyl}-2-propenyl)-2,4,6(1H, 3H, 5H)-pyrimidinetrione | 556051-99-1

• 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-methyl-5-((2E)-3-{4-[(2-methyl-4-quinolinyl)methoxy]phenyl}-2-propenyl)-2,4,6(1H, 3H, 5H)-pyrimidinetrione
• 英文别名: 5-methyl-5-((2E)-3-{4-[(2-methyl-4-quinolinyl)methoxy]phenyl}-2-propenyl)-2,4,6(1H,3H,5H)-pyrimidinetrione；5-(4-((2-methylquinolin-4-yl)methoxy)cinnamyl)-5-methylpyrimidine-2,4,6(1H,3H,5H)-trione；5-methyl-5-[(E)-3-[4-[(2-methylquinolin-4-yl)methoxy]phenyl]prop-2-enyl]-1,3-diazinane-2,4,6-trione
• CAS: 556051-99-1
• 化学式: C₂₅H₂₃N₃O₄
• 分子量: 429.475
• InChiKey: MHMXZGVHZDNEMP-AATRIKPKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  32
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  97.4
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-methyl-5-((2E)-3-{4-[(2-methyl-4-quinolinyl)methoxy]phenyl}-2-propenyl)-2,4,6(1H, 3H, 5H)-pyrimidinetrione 在 palladium diacetate 高氯酸 、 对苯醌 作用下， 以 水 、 乙腈 为溶剂， 反应 96.0h， 以71%的产率得到5-methyl-5-(3-{4-[(2-methyl-4-quinolinyl)methoxy]phenyl}-3-oxopropyl)-2,4,6(1H,3H,5H)-pyrimidinetrione
  参考文献：
  名称：

  Barbituric acid derivatives as inhibitors of TNF-alpha converting enzyme (TACE) and/or matrix metalloproteinases

  摘要：

  本申请描述了式I的新型巴比妥酸衍生物： 1 或其药用可接受的盐或前药形式，其中A、B、L、R 1 、R 2 、R 3 、R 4 、R 5 、n、W、U、X、Y、Z、U a 、X a 、Y a 和Z a 在本规范中定义，这些衍生物可用作TNF-α转化酶（TACE）和基质金属蛋白酶（MMP）抑制剂。

  公开号：

  US20030229084A1
• 作为产物：
  描述：

  2-[(E)-3-(4-Hydroxy-phenyl)-allyl]-2-methyl-malonic acid dimethyl ester 在 caesium carbonate 、 magnesium methanolate 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 5-methyl-5-((2E)-3-{4-[(2-methyl-4-quinolinyl)methoxy]phenyl}-2-propenyl)-2,4,6(1H, 3H, 5H)-pyrimidinetrione
  参考文献：
  名称：

  Discovery of low nanomolar non-hydroxamate inhibitors of tumor necrosis factor-α converting enzyme (TACE)

  摘要：

  Using a pyrimidine-2,4,6-trione motif as a zinc-binding group, a series of selective inhibitors of tumor necrosis factor-alpha converting enzyme (TACE) was discovered. Optimization of initial lead I resulted in a potent inhibitor (51), with an IC50 of 2 nM in a porcine TACE assay. To the best of our knowledge, compound 51 and related analogues represent first examples of non-hydroxamate-based inhibitors of TACE with single digit nanomolar potency. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.09.048

文献信息

• Barbituric acid derivatives as inhibitors of TNF-alpha converting enzyme (TACE) and/or matrix metalloproteinases
  申请人：——

  公开号：US20030229084A1

  公开（公告）日：2003-12-11

  The present application describes novel barbituric acid derivatives of formula I: 1 or pharmaceutically acceptable salt or prodrug forms thereof, wherein A, B, L, R 1 , R 2 , R 3 , R 4 , R 5 , n, W, U, X, Y, Z, U a , X a , Y a , and Z a are defined in the present specification, which are useful as TNF-&agr; converting enzyme (TACE) and matrix metalloproteinases (MMP) inhibitors.

  本申请描述了式I的新型巴比妥酸衍生物： 1 或其药用可接受的盐或前药形式，其中A、B、L、R 1 、R 2 、R 3 、R 4 、R 5 、n、W、U、X、Y、Z、U a 、X a 、Y a 和Z a 在本规范中定义，这些衍生物可用作TNF-α转化酶（TACE）和基质金属蛋白酶（MMP）抑制剂。
• US6936620B2
  申请人：——

  公开号：US6936620B2

  公开（公告）日：2005-08-30
• Discovery of low nanomolar non-hydroxamate inhibitors of tumor necrosis factor-α converting enzyme (TACE)
  作者：James J.-W. Duan、Lihua Chen、Zhonghui Lu、Bin Jiang、Naoyuki Asakawa、James E. Sheppeck、Rui-Qin Liu、Maryanne B. Covington、William Pitts、Soong-Hoon Kim、Carl P. Decicco

  DOI：10.1016/j.bmcl.2006.09.048

  日期：2007.1

  Using a pyrimidine-2,4,6-trione motif as a zinc-binding group, a series of selective inhibitors of tumor necrosis factor-alpha converting enzyme (TACE) was discovered. Optimization of initial lead I resulted in a potent inhibitor (51), with an IC50 of 2 nM in a porcine TACE assay. To the best of our knowledge, compound 51 and related analogues represent first examples of non-hydroxamate-based inhibitors of TACE with single digit nanomolar potency. (c) 2006 Elsevier Ltd. All rights reserved.