(7S,8R)-N-hydroxy-8-({4-[(2-methyl-4-quinolinyl)methoxy]benzoyl}amino)-1,4-dioxaspiro[4.4]nonane-7-carboxamide | 362489-02-9

• 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: (7S,8R)-N-hydroxy-8-({4-[(2-methyl-4-quinolinyl)methoxy]benzoyl}amino)-1,4-dioxaspiro[4.4]nonane-7-carboxamide
• 英文别名: 1,3-Dioxolane beta-amino hydroxamate, 1；(7S,8R)-N-hydroxy-8-[[4-[(2-methylquinolin-4-yl)methoxy]benzoyl]amino]-1,4-dioxaspiro[4.4]nonane-7-carboxamide
• CAS: 362489-02-9
• 化学式: C₂₆H₂₇N₃O₆
• 分子量: 477.517
• InChiKey: KRGIXMSVPSMLII-JTHBVZDNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  35
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  119
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (7S,8R)-N-hydroxy-8-({4-[(2-methyl-4-quinolinyl)methoxy]benzoyl}amino)-1,4-dioxaspiro[4.4]nonane-7-carboxamide 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 以99%的产率得到N-{(1R,2S)-2-[(hydroxyamino)carbonyl]-4-oxocyclopentyl}-4-[(2-methyl-4-quinolinyl)methoxy]benzamide
  参考文献：
  名称：

  α,β-Cyclic-β-benzamido hydroxamic acids: Novel templates for the design, synthesis, and evaluation of selective inhibitors of TNF-α converting enzyme (TACE)

  摘要：

  Selective inhibitors of TNF-alpha Converting Enzyme (TACE) based on (1R,2S)-cyclopentyl, (3S,4S)-pyrrolidinyl, and (3R,4S)-tetrahydrofuranyl beta-benzamido hydroxamic acids have been synthesized and evaluated. This study has led to the discovery of novel inhibitors whose profiles include activity against TACE in an enzyme assay, potency in the suppression of LPS-stimulated TNF-alpha in human whole blood, selectivity against a panel of MMPs and oral bioavailability. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.11.059
• 作为产物：
  描述：

  methyl (7S,8R)-8-(4-((2-methylquinolin-4-yl)methoxy)benzamido)-1,4-dioxaspiro[4.4]nonane-7-carboxylate 在 氢氧化钾 、 羟胺 作用下， 以 甲醇 为溶剂， 生成 (7S,8R)-N-hydroxy-8-({4-[(2-methyl-4-quinolinyl)methoxy]benzoyl}amino)-1,4-dioxaspiro[4.4]nonane-7-carboxamide
  参考文献：
  名称：

  α,β-Cyclic-β-benzamido hydroxamic acids: Novel templates for the design, synthesis, and evaluation of selective inhibitors of TNF-α converting enzyme (TACE)

  摘要：

  Selective inhibitors of TNF-alpha Converting Enzyme (TACE) based on (1R,2S)-cyclopentyl, (3S,4S)-pyrrolidinyl, and (3R,4S)-tetrahydrofuranyl beta-benzamido hydroxamic acids have been synthesized and evaluated. This study has led to the discovery of novel inhibitors whose profiles include activity against TACE in an enzyme assay, potency in the suppression of LPS-stimulated TNF-alpha in human whole blood, selectivity against a panel of MMPs and oral bioavailability. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.11.059

文献信息

• Spiro-cyclic beta-amino acid derivatives as inhibitors of matrix metalloproteases and TNF-alpha converting enzyme (TACE)
  申请人：——

  公开号：US20030087882A1

  公开（公告）日：2003-05-08

  The present application describes novel spiro-cyclic &bgr;-amino acid derivatives of formula I: 1 or pharmaceutically acceptable salt forms thereof, wherein ring B is a 3-13 membered carbocycle or heterocycle, ring C forms a 3-11 membered spiro-carbocycle or spiro-heterocycleon ring B, and the other variables are defined in the present specification, which are useful as as matrix metalloproteinases (MMP), TNF-&agr; converting enzyme (TACE), and/or aggrecanase inhibitors.

  本申请描述了新颖的式I的螺环式&bgr;-氨基酸衍生物或其药用盐形式，其中环B是3-13成员碳环或杂环，环C形成3-11成员的螺环碳环或螺环杂环在环B上，并且其他变量在本规范中定义，这些衍生物可用作基质金属蛋白酶（MMP）、TNF-&agr;转化酶（TACE）和/或聚集素酶抑制剂。
• US6720329B2
  申请人：——

  公开号：US6720329B2

  公开（公告）日：2004-04-13
• US6962938B2
  申请人：——

  公开号：US6962938B2

  公开（公告）日：2005-11-08
• α,β-Cyclic-β-benzamido hydroxamic acids: Novel templates for the design, synthesis, and evaluation of selective inhibitors of TNF-α converting enzyme (TACE)
  作者：Gregory R. Ott、Naoyuki Asakawa、Zhonghui Lu、Rui-Qin Liu、Maryanne B. Covington、Krishna Vaddi、Mingxin Qian、Robert C. Newton、David D. Christ、James M. Traskos、Carl P. Decicco、James J.-W. Duan

  DOI：10.1016/j.bmcl.2007.11.059

  日期：2008.1

  Selective inhibitors of TNF-alpha Converting Enzyme (TACE) based on (1R,2S)-cyclopentyl, (3S,4S)-pyrrolidinyl, and (3R,4S)-tetrahydrofuranyl beta-benzamido hydroxamic acids have been synthesized and evaluated. This study has led to the discovery of novel inhibitors whose profiles include activity against TACE in an enzyme assay, potency in the suppression of LPS-stimulated TNF-alpha in human whole blood, selectivity against a panel of MMPs and oral bioavailability. (c) 2007 Elsevier Ltd. All rights reserved.