N-hydroxy-4-[({4-[(2-methyl-4-quinolinyl)methoxy]benzoyl}amino)methyl]-1-propyl-4-piperidinecarboxamide

• 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: N-hydroxy-4-[({4-[(2-methyl-4-quinolinyl)methoxy]benzoyl}amino)methyl]-1-propyl-4-piperidinecarboxamide
• 英文别名: N-hydroxy-4-((4-((2-methylquinolin-4-yl)methoxy)benzamido)methyl)-1-propylpiperidine-4-carboxamide；N-hydroxy-4-[[[4-[(2-methylquinolin-4-yl)methoxy]benzoyl]amino]methyl]-1-propylpiperidine-4-carboxamide
• 化学式: C₂₈H₃₄N₄O₄
• 分子量: 490.602
• InChiKey: GTCRWKBEGBSXDD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  36
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  104
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  N-Boc-4-氰基哌啶-4-甲酸甲酯 在 platinum(IV) oxide N-甲基吗啉 、 盐酸 、 氢氧化钾 、 NaH(OAc)3 、 氢气 、 羟胺 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 三氟乙酸 作用下， 以 甲醇 、 二氯甲烷 、 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 N-hydroxy-4-[({4-[(2-methyl-4-quinolinyl)methoxy]benzoyl}amino)methyl]-1-propyl-4-piperidinecarboxamide
  参考文献：
  名称：

  Synthesis and structure–activity relationship of a novel, achiral series of TNF-α converting enzyme inhibitors

  摘要：

  A novel series of achiral TNF-alpha converting enzyme (TACE) inhibitors has been discovered. These compounds exhibited activities from 0.35 to 11 nM in a porcine TACE assay and inhibited TNF-alpha production in an LPS-stimulated whole blood assay with an IC50 value of 23 nM for the most potent one. They also have excellent selectivities over related metalloproteases including aggrecanases. (C) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.02.015

文献信息

• Beta-Amino-Acid derivatives as inhibitors of matrix metalloproteases and TNF-Alpha
  申请人：——

  公开号：US20020013341A1

  公开（公告）日：2002-01-31

  The present application describes novel &bgr;-amino acid derivatives of formula I: 1 or pharmaceutically acceptable salt or prodrug forms thereof, wherein A, X, Z, U a , X a , Y a , Z a , R 1 , R 2 , R 3 , R 4 , and R 4a are defined in the present specification, which are useful as metalloprotease and/or as TNF-&agr; inhibitors.

  本申请描述了式I的新型β-氨基酸衍生物： 1 或其药用可接受的盐或前药形式，其中A、X、Z、U a 、X a 、Y a 、Z a 、R 1 、R 2 、R 3 、R 4 和R 4a 在本规范中有定义，这些衍生物可用作金属蛋白酶和/或TNF-α抑制剂。
• Beta-amino acid derivatives as inhibitors of matrix metalloproteases and TNF-alpha
  申请人：——

  公开号：US20040072802A1

  公开（公告）日：2004-04-15

  The present application describes novel &bgr;-amino acid derivatives of formula I: 1 or pharmaceutically acceptable salt or prodrug forms thereof, wherein A, X, Z, U a , X a , Y a , Z a , R 1 , R 2 , R 3 , R 4 , and R 4a are defined in the present specification, which are useful as metalloprotease and/or as TNF-&agr; inhibitors.

  本申请描述了式I的新颖β-氨基酸衍生物：1或其药用可接受的盐或前药形式，其中A、X、Z、Ua、Xa、Ya、Za、R1、R2、R3、R4和R4a在本规范中有定义，这些衍生物可用作金属蛋白酶和/或TNF-α抑制剂。
• BETA-AMINO ACID DERIVATIVES AS INHIBITORS OF MATRIX METALLOPROTEASES AND TNF-ALPHA
  申请人：Bristol-Myers Squibb Pharma Company

  公开号：EP1263756B1

  公开（公告）日：2004-02-25
• US6495565B2
  申请人：——

  公开号：US6495565B2

  公开（公告）日：2002-12-17
• Synthesis and structure–activity relationship of a novel, achiral series of TNF-α converting enzyme inhibitors
  作者：John L. Gilmore、Bryan W. King、Cathy Harris、Thomas Maduskuie、Stephen E. Mercer、Rui-Qin Liu、Maryanne B. Covington、Mingxin Qian、Maria D. Ribadeneria、Krishna Vaddi、James M. Trzaskos、Robert C. Newton、Carl P. Decicco、James J.-W. Duan

  DOI：10.1016/j.bmcl.2006.02.015

  日期：2006.5

  A novel series of achiral TNF-alpha converting enzyme (TACE) inhibitors has been discovered. These compounds exhibited activities from 0.35 to 11 nM in a porcine TACE assay and inhibited TNF-alpha production in an LPS-stimulated whole blood assay with an IC50 value of 23 nM for the most potent one. They also have excellent selectivities over related metalloproteases including aggrecanases. (C) 2006 Elsevier Ltd. All rights reserved.