(4S)-4-benzyl-3-<(2'R)-2'-<(tert-butoxycarbonyl)methyl>-6'-(4-chlorophenoxy)hexanoyl>-2-oxazolidone | 169270-15-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: (4S)-4-benzyl-3-<(2'R)-2'-<(tert-butoxycarbonyl)methyl>-6'-(4-chlorophenoxy)hexanoyl>-2-oxazolidone
• 英文别名: tert-butyl (3R)-3-[(4S)-4-benzyl-2-oxo-1,3-oxazolidine-3-carbonyl]-7-(4-chlorophenoxy)heptanoate
• CAS: 169270-15-9
• 化学式: C₂₈H₃₄ClNO₆
• 分子量: 516.034
• InChiKey: CMGCVWYXJADPIT-GGAORHGYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  36
• 可旋转键数：
  13
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  82.1
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (4S)-4-benzyl-3-<(2'R)-2'-<(tert-butoxycarbonyl)methyl>-6'-(4-chlorophenoxy)hexanoyl>-2-oxazolidone 在 lithium hydroxide 、 氰基磷酸二乙酯 、 水 、 双氧水 、 三乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 (R)-7-(4-Chloro-phenoxy)-3-((S)-2,2-dimethyl-1-phenethylcarbamoyl-propylcarbamoyl)-heptanoic acid
  参考文献：
  名称：

  Inhibition of Matrix Metalloproteinases by Hydroxamates Containing Heteroatom-Based Modifications of the P1' Group

  摘要：

  In this study, structure-based drug design of matrix metalloproteinase inhibitors [human fibroblast collagenase (HFC), human fibroblast stromelysin (HFS), and human neutrophil collagenase (HNC)] was utilized in the development of potent hydroxamates which contain novel, heteroatom-based modifications of the P-1' group. A series containing a P-1' butyramide group resulted in a nanomolar potent and selective HNC inhibitor as well as a dual HFS/HNC inhibitor. Benzylic others with a four- or five-carbon methylene linker in the P-1' position also produced nanomolar potent HFS/HNC inhibition and micromolar potent HFC inhibition as expected. Surprisingly, the phenolic ethers of the same overall length as the benzylic ethers showed nanomolar potencies against HFC, as well as HFS and HNC. The potency profile of the phenolic ethers was optimized by structure-activity relationships of the phenolic group and the C-terminal amide. These inhibitors may help elucidate the in vivo roles of matrix metalloproteinases in normal and disease states.

  DOI：

  10.1021/jm00014a010
• 作为产物：
  描述：

  1,6-己二醇 在 palladium dihydroxide 重铬酸吡啶 、 正丁基锂 、 草酰氯 、 1,4-环己二烯 、 sodium hydride 、 二异丙胺 、 N,N-二甲基甲酰胺 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 为溶剂， 反应 18.92h， 生成 (4S)-4-benzyl-3-<(2'R)-2'-<(tert-butoxycarbonyl)methyl>-6'-(4-chlorophenoxy)hexanoyl>-2-oxazolidone
  参考文献：
  名称：

  Inhibition of Matrix Metalloproteinases by Hydroxamates Containing Heteroatom-Based Modifications of the P1' Group

  摘要：

  In this study, structure-based drug design of matrix metalloproteinase inhibitors [human fibroblast collagenase (HFC), human fibroblast stromelysin (HFS), and human neutrophil collagenase (HNC)] was utilized in the development of potent hydroxamates which contain novel, heteroatom-based modifications of the P-1' group. A series containing a P-1' butyramide group resulted in a nanomolar potent and selective HNC inhibitor as well as a dual HFS/HNC inhibitor. Benzylic others with a four- or five-carbon methylene linker in the P-1' position also produced nanomolar potent HFS/HNC inhibition and micromolar potent HFC inhibition as expected. Surprisingly, the phenolic ethers of the same overall length as the benzylic ethers showed nanomolar potencies against HFC, as well as HFS and HNC. The potency profile of the phenolic ethers was optimized by structure-activity relationships of the phenolic group and the C-terminal amide. These inhibitors may help elucidate the in vivo roles of matrix metalloproteinases in normal and disease states.

  DOI：

  10.1021/jm00014a010