(4R)-1-[4-(4-fluorophenoxy)benzyl]-2-oxo-imidazolidine-4-carboxylic acid (2-trimethylsilanylethoxy)amide | 361146-55-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (4R)-1-[4-(4-fluorophenoxy)benzyl]-2-oxo-imidazolidine-4-carboxylic acid (2-trimethylsilanylethoxy)amide
• 英文别名: (4R)-1-[[4-(4-fluorophenoxy)phenyl]methyl]-2-oxo-N-(2-trimethylsilylethoxy)imidazolidine-4-carboxamide
• CAS: 361146-55-6
• 化学式: C₂₂H₂₈FN₃O₄Si
• 分子量: 445.566
• InChiKey: FILBKYCROBHCNH-HXUWFJFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  31
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  79.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (4R)-1-[4-(4-fluorophenoxy)benzyl]-2-oxo-imidazolidine-4-carboxylic acid (2-trimethylsilanylethoxy)amide 在 ammonium chloride 、 trifluoroborane diethyl ether 作用下， 以 二氯甲烷 为溶剂， 以47%的产率得到(4R)-1-[4-(4-Fluorophenoxy)benzyl]-2-oxo-imidazolidine-4-carboxylic acid hydroxyamide
  参考文献：
  名称：

  2-oxo-imidazolidine-4-carboxylic acid hydroxamide compounds that inhibit matrix metalloproteinases

  摘要：

  本发明涉及一种化合物，其化学式为1，其中R1、R2、R3和R4如上所定义，并且其可接受的药物盐和溶剂化物，例如作为基质金属蛋白酶抑制剂。本发明还涉及包括这些化合物的药物组合物和用于治疗疾病的方法，例如骨关节炎、类风湿性关节炎、癌症、骨质疏松症、组织溃疡、再狭窄、牙周病、炎症、表皮松解症、巩膜炎、中风、阿尔茨海默病等，其特征是基质金属蛋白酶活性不当。还公开了化合物(I)的合成方法。

  公开号：

  US20010041710A1
• 作为产物：
  描述：

  (4R)-1-[4-(4-fluorophenoxy)benzyl]-2-oxo-imidazolidine-4-carboxylic acid tert-butyl ester 在 乙胺嗪 、 1-羟基苯并三唑 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 (4R)-1-[4-(4-fluorophenoxy)benzyl]-2-oxo-imidazolidine-4-carboxylic acid (2-trimethylsilanylethoxy)amide
  参考文献：
  名称：

  Design and synthesis of 2-oxo-imidazolidine-4-carboxylic acid hydroxyamides as potent matrix metalloproteinase-13 inhibitors

  摘要：

  A novel series of imidazolidinone-based matrix metalloproteinase (MMP) inhibitors was discovered by structural modification of pyrrolidinone 1a. Potent inhibition of MMP-13 was exhibited by the analogues having 4-(4-fluorophenoxy)phenyl (4a, IC50 = 3 nM) and 4-(naphth-2-yloxy)phenyl (4h, IC50 - 4 nM) as Pl ' groups. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(01)00187-1

文献信息

• 2-oxo-imidazolidine-4-carboxylic acid hydroxamide compounds that inhibit matrix metalloproteinases
  申请人：——

  公开号：US20010041710A1

  公开（公告）日：2001-11-15

  The present invention relates to a compound of the formula 1 wherein R 1 , R 2 , R 3 and R 4 are as defined above, and pharmaceutically acceptable salts and solvates thereof, that are useful, for example, as matrix metalloproteinase inhibitors. The present invention is also directed to pharmaceutical compositions comprising such compounds and methods of treatment for diseases such as osteoarthritis, rheumatoid arthritis, cancer, osteoporosis, tissue ulceration, restinosis, periodontal disease, inflammation, epidermolysis bullosa, scleritis, stroke, Alzheimer's disease, and the like, characterized by inappropriate matrix metalloproteinase activity. Processes for the synthesis of compounds of formula (I) are also disclosed.

  本发明涉及一种公式1的化合物，其中R1，R2，R3和R4如上所定义，并且其药学上可接受的盐和溶剂，例如作为基质金属蛋白酶抑制剂。本发明还涉及包含这种化合物的制药组合物和治疗疾病的方法，例如骨关节炎，类风湿性关节炎，癌症，骨质疏松，组织溃疡，再狭窄，牙周疾病，炎症，表皮松解性疾病，巩膜炎，中风，阿尔茨海默病等，其特征是基质金属蛋白酶活性不适当。本发明还公开了化合物公式（I）的合成方法。
• Design and synthesis of 2-oxo-imidazolidine-4-carboxylic acid hydroxyamides as potent matrix metalloproteinase-13 inhibitors
  作者：Ralph P Robinson、Ellen R Laird、Kathleen M Donahue、Lori L Lopresti-Morrow、Peter G Mitchell、Matthew R Reese、Lisa M Reeves、Amber I Rouch、Ethan J Stam、Sue A Yocum

  DOI：10.1016/s0960-894x(01)00187-1

  日期：2001.5

  A novel series of imidazolidinone-based matrix metalloproteinase (MMP) inhibitors was discovered by structural modification of pyrrolidinone 1a. Potent inhibition of MMP-13 was exhibited by the analogues having 4-(4-fluorophenoxy)phenyl (4a, IC50 = 3 nM) and 4-(naphth-2-yloxy)phenyl (4h, IC50 - 4 nM) as Pl ' groups. (C) 2001 Elsevier Science Ltd. All rights reserved.