(R)-3-((S)-1-Methylcarbamoyl-2-phenyl-ethylcarbamoyl)-6-phenethylcarbamoyl-hexanoic acid tert-butyl ester | 169270-10-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (R)-3-((S)-1-Methylcarbamoyl-2-phenyl-ethylcarbamoyl)-6-phenethylcarbamoyl-hexanoic acid tert-butyl ester
• 英文别名: tert-butyl (3R)-3-[[(2S)-1-(methylamino)-1-oxo-3-phenylpropan-2-yl]carbamoyl]-7-oxo-7-(2-phenylethylamino)heptanoate
• CAS: 169270-10-4
• 化学式: C₃₀H₄₁N₃O₅
• 分子量: 523.673
• InChiKey: UHMUSNIOTWSMPD-RPBOFIJWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  38
• 可旋转键数：
  16
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  114
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (R)-3-((S)-1-Methylcarbamoyl-2-phenyl-ethylcarbamoyl)-6-phenethylcarbamoyl-hexanoic acid tert-butyl ester 在 N-甲基吗啉 、 O-(三甲基硅)羟胺 、 水 、 三氟乙酸 作用下， 以 四氢呋喃 为溶剂， 反应 2.33h， 生成 (R)-3-((S)-1-Methylcarbamoyl-2-phenyl-ethylcarbamoyl)-heptanedioic acid 1-hydroxyamide 7-(phenethyl-amide)
  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 lithium hydroxide 、 重铬酸吡啶 、 正丁基锂 、 草酰氯 、 氰基磷酸二乙酯 、 1,4-环己二烯 、 双氧水 、 sodium hydride 、 三乙胺 、 二异丙胺 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 25.92h， 生成 (R)-3-((S)-1-Methylcarbamoyl-2-phenyl-ethylcarbamoyl)-6-phenethylcarbamoyl-hexanoic acid tert-butyl ester
  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