(4S)-4-benzyl-3-<(2'R)-2'-<(tert-butoxycarbonyl)methyl>-6'-azidohexanoyl>-2-oxazolidone | 168973-97-5

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: (4S)-4-benzyl-3-<(2'R)-2'-<(tert-butoxycarbonyl)methyl>-6'-azidohexanoyl>-2-oxazolidone
• 英文别名: (R)-5-azido-3-((S)-4-benzyl-2-oxooxazolidine-3-carbonyl)heptanoic acid tert-butyl ester；tert-butyl (3R)-7-azido-3-[(4S)-4-benzyl-2-oxo-1,3-oxazolidine-3-carbonyl]heptanoate
• CAS: 168973-97-5
• 化学式: C₂₂H₃₀N₄O₅
• 分子量: 430.504
• InChiKey: ZZNQSRWKPDHNPZ-MSOLQXFVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  31
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  87.3
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (4S)-4-benzyl-3-<(2'R)-2'-<(tert-butoxycarbonyl)methyl>-6'-azidohexanoyl>-2-oxazolidone 在 palladium on activated charcoal lithium hydroxide 、 氰基磷酸二乙酯 、 氢气 、 双氧水 、 三乙胺 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 为溶剂， -10.0~25.0 ℃ 、206.84 kPa 条件下， 反应 5.2h， 生成 N-[(2R)-2-(tert-Butoxycarbonylmethyl)-6-(amino)hexanoyl]-L-phenylalanine N-methylamide
  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 4-二甲氨基吡啶 、 重铬酸吡啶 、 正丁基锂 、 sodium azide 、 草酰氯 、 1,4-环己二烯 、 四丁基碘化铵 、 sodium hydride 、 三乙胺 、 二异丙胺 、 N,N-二甲基甲酰胺 作用下， 以 乙醇 、 二氯甲烷 、 水 、 甲苯 为溶剂， 反应 19.92h， 生成 (4S)-4-benzyl-3-<(2'R)-2'-<(tert-butoxycarbonyl)methyl>-6'-azidohexanoyl>-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

文献信息

• Conjugates of Modified Cryptophycins and RGD-Peptides Enter Target Cells by Endocytosis
  作者：Markus Nahrwold、Christine Weiß、Tobias Bogner、Felix Mertink、Jens Conradi、Benedikt Sammet、Ralf Palmisano、Soledad Royo Gracia、Thomas Preuße、Norbert Sewald

  DOI：10.1021/jm301346z

  日期：2013.3.14

  Tumor targeting anticancer drug conjugates that contain a tumor recognition motif (homing device) are of high current relevance. Cryptophycins, naturally occurring cytotoxic cyclo-depsipeptides, have been modified by total synthesis to provide analogues suitable for conjugation to peptide-based homing devices. An array of functionalized beta(2)-amino acids was synthesized and incorporated into cryptophycins. All analogues proved to be highly active in the cytotoxicity assay using the human cervix carcinoma cell line KB-3-1 and its multidrug-resistant subclone KB-V1. Conformational analysis of cryptophycin-52 and two synthetic analogues was performed by NMR and MD methods to obtain information on the influence of the unit C configuration on the overall conformation. An azide-functionalized cryptophycin was connected by CuAAC to an alkyne-containing fluorescently labeled cyclic RGD-peptide as the homing device for internalization studies. Confocal fluorescence microscopy proved integrin-mediated internalization by endocytosis and final lysosomal localization of the cryptophycin prodrug.
• US5514716A
  申请人：——

  公开号：US5514716A

  公开（公告）日：1996-05-07
• US5618844A
  申请人：——

  公开号：US5618844A

  公开（公告）日：1997-04-08
• Inhibition of Matrix Metalloproteinases by Hydroxamates Containing Heteroatom-Based Modifications of the P1' Group
  作者：Madhusudhan R. Gowravaram、Jeffrey S. Johnson、Daniel Delecki、Ewell R. Cook、Bruce E. Tomczuk、Arup K. Ghose、Alan M. Mathiowetz、John C. Spurlino、Byron Rubin、Douglas L. Smith、Tricia Pulvino、Robert C. Wahl

  DOI：10.1021/jm00014a010

  日期：1995.7

  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.