methyl 2-[4-(benzyloxy)phenyl]-2-methyl-4-oxobutanoate | 223406-00-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: methyl 2-[4-(benzyloxy)phenyl]-2-methyl-4-oxobutanoate
• 英文别名: Methyl 2-methyl-4-oxo-2-(4-phenylmethoxyphenyl)butanoate
• CAS: 223406-00-6
• 化学式: C₁₉H₂₀O₄
• 分子量: 312.365
• InChiKey: FYZRWKMVVZLSQL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  23
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 2-[4-(benzyloxy)phenyl]-2-methyl-4-oxobutanoate 在 palladium dihydroxide 氢气 、 caesium carbonate 、 溶剂黄146 、 sodium iodide 、 锌 作用下， 以 甲醇 、 二甲基亚砜 为溶剂， 反应 2.5h， 生成 (R)-2-{(S)-3-Methyl-3-[4-(2-methyl-quinolin-4-ylmethoxy)-phenyl]-2-oxo-pyrrolidin-1-yl}-propionic acid methyl ester
  参考文献：
  名称：

  Discovery of γ-Lactam Hydroxamic Acids as Selective Inhibitors of Tumor Necrosis Factor α Converting Enzyme:  Design, Synthesis, and Structure−Activity Relationships

  摘要：

  New gamma-lactam. TACE inhibitors were designed from known MMP inhibitors. A homology model of TACE was built and examined to identify the S1' site as the key area for TACE selectivity over MMPs. Rational exploration of the P1'-S1' interactions resulted in the discovery of the 3,5-disubstituted benzyl ether as a TACE-selective P1' group. Further optimization led to the discovery of IK682 as a selective and orally bioavailable TACE inhibitor.

  DOI：

  10.1021/jm0255670
• 作为产物：
  描述：

  methyl 2-(4-benzyloxyphenyl)propionate 在 sodium hexamethyldisilazane 、 臭氧 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 4.0h， 生成 methyl 2-[4-(benzyloxy)phenyl]-2-methyl-4-oxobutanoate
  参考文献：
  名称：

  Discovery of γ-Lactam Hydroxamic Acids as Selective Inhibitors of Tumor Necrosis Factor α Converting Enzyme:  Design, Synthesis, and Structure−Activity Relationships

  摘要：

  New gamma-lactam. TACE inhibitors were designed from known MMP inhibitors. A homology model of TACE was built and examined to identify the S1' site as the key area for TACE selectivity over MMPs. Rational exploration of the P1'-S1' interactions resulted in the discovery of the 3,5-disubstituted benzyl ether as a TACE-selective P1' group. Further optimization led to the discovery of IK682 as a selective and orally bioavailable TACE inhibitor.

  DOI：

  10.1021/jm0255670

文献信息

• Matrix metalloproteinase inhibitors
  申请人：Bristol-Myers Squibb Pharma Company

  公开号：US06656448B1

  公开（公告）日：2003-12-02

  Thus the present invention describes diagnostic agents comprising a diagnostic metal and a compound, wherein the compound comprises: 1-10 targeting moieties;a chelator; and 0-1 linking groups between the targeting moiety and chelator; wherein the targeting moiety is a matrix metalloproteinase inhibitor; and wherein the chelator is capable of conjugating to the diagnostic metal. The present invention also provides novel compositions of the compounds of the invention, kits, and their uses in diagnosis of diseases associated with MMPs.

  因此，本发明描述了包含诊断金属和化合物的诊断试剂，其中该化合物包括：1-10个靶向基团；螯合剂；以及靶向基团和螯合剂之间的0-1个连接基团；其中靶向基团是基质金属蛋白酶抑制剂；螯合剂能够与诊断金属结合。本发明还提供了该化合物的新型组合物、试剂盒以及它们在与基质金属蛋白酶相关的疾病诊断中的用途。
• Barbituric acid derivatives as inhibitors of TNF-alpha converting enzyme (TACE) and/or matrix metalloproteinases
  申请人：——

  公开号：US20030166647A1

  公开（公告）日：2003-09-04

  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 , W, 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 metalloproteinses (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、R1、W、Z、Ua、Xa、Ya和Za如本规范中定义，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。
• [EN] BARBITURIC ACID DERIVATIVES AS INHIBITORS OF TNF- DOLLAR G(A) CONVERTING ENZYME (TACE) AND/OR MATRIX METALLOPROTEINASES<br/>[FR] DERIVES D'ACIDE BARBITURIQUE UTILISES COMME INHIBITEURS DE L'ENZYME DE CONVERSION DU TNF- DOLLAR G(A) (TACE) ET/OU DE METALLOPROTEINASES MATRICIELLES
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2003053940A1

  公开（公告）日：2003-07-03

  The present application describes novel barbituric acid derivatives of formula (I), or pharmaceutically acceptable salt or prodrug forms thereof, wherein A, B, L, R1, W, Z, U?a, Xa, Ya, and Za¿ are defined in the present specification, which are useful as TNF-α converting enzyme (TACE) and matrix metalloproteinases (MMP) inhibitors.

  本申请描述了新的巴比妥酸衍生物的公式（I），或其药学上可接受的盐或前药形式，其中A、B、L、R1、W、Z、Ua、Xa、Ya和Za在本说明中有定义，它们可用作TNF-α转化酶（TACE）和基质金属蛋白酶（MMP）抑制剂。
• Hydantoin derivatives and deren verwendung als tace inhibitoren
  申请人：Burrows Nicholas Jeremy

  公开号：US20060063818A1

  公开（公告）日：2006-03-23

  Hydantoin derivatives of Formula (1) that are useful in the inhibition of metalloproteinases and in particular in the inhibition of TNF-α Converting Enzyme (TACE).

  公式（1）的咪唑二酮衍生物在抑制金属蛋白酶特别是抑制TNF-α转化酶（TACE）方面是有用的。
• 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.