N¹-benzyloxy-2(R)-benzyloxymethyl-N⁴-(2,2-dimethyl-1(S)-methylcarbamoylpropyl)-3(S)-(4-methoxyphenyl)succinamide | 439112-52-4

• 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: N¹-benzyloxy-2(R)-benzyloxymethyl-N⁴-(2,2-dimethyl-1(S)-methylcarbamoylpropyl)-3(S)-(4-methoxyphenyl)succinamide
• 英文别名: (2S,3R)-N-[(2S)-3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl]-2-(4-methoxyphenyl)-N'-phenylmethoxy-3-(phenylmethoxymethyl)butanediamide
• CAS: 439112-52-4
• 化学式: C₃₃H₄₁N₃O₆
• 分子量: 575.705
• InChiKey: DLGMXBNNTCTWQG-ZGIBFIJWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  42
• 可旋转键数：
  15
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  115
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N¹-benzyloxy-2(R)-benzyloxymethyl-N⁴-(2,2-dimethyl-1(S)-methylcarbamoylpropyl)-3(S)-(4-methoxyphenyl)succinamide 在 Pd-BaSO₄ 氢气 作用下， 以 甲醇 为溶剂， 反应 6.0h， 以63%的产率得到(2R,3S)-N4-[(S)-2,2-dimethyl-1-(methylcarbamoyl)propyl]-N1-hydroxy-2-hydroxymethyl-3-(4-methoxyphenyl)succinamide
  参考文献：
  名称：

  β-Aryl-Succinic Acid Hydroxamates as Dual Inhibitors of Matrix Metalloproteinases and Tumor Necrosis Factor Alpha Converting Enzyme

  摘要：

  Novel hydroxamate inhibitors of tumor necrosis factor converting enzyme (TACE) and matrix metalloproteases (MMPs) have been synthesized via the Claisen-Ireland rearrangement. Aryl residues have been introduced to fill the enzyme's P1' specificity pocket. The best compound inhibits MMPs and TACE with nanomolar potency and inhibits the release of TNFalpha from cells with an IC50 of 48 nM. Oral administration to rats inhibits the LPS-induced plasma TNFa levels with an ED50 of 1 mg/kg.

  DOI：

  10.1021/jm0110993
• 作为产物：
  描述：

  L-tert-leucine methylamide hydrochloride 在 sodium chlorite 、 sodium periodate 、 sodium dihydrogenphosphate 、 四氧化锇 、 2-甲基-2-丁烯 、 1-羟基苯并三唑 、 N-甲基吗啉氧化物 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 、 丙酮 、 叔丁醇 为溶剂， 反应 76.0h， 生成 N¹-benzyloxy-2(R)-benzyloxymethyl-N⁴-(2,2-dimethyl-1(S)-methylcarbamoylpropyl)-3(S)-(4-methoxyphenyl)succinamide
  参考文献：
  名称：

  β-Aryl-Succinic Acid Hydroxamates as Dual Inhibitors of Matrix Metalloproteinases and Tumor Necrosis Factor Alpha Converting Enzyme

  摘要：

  Novel hydroxamate inhibitors of tumor necrosis factor converting enzyme (TACE) and matrix metalloproteases (MMPs) have been synthesized via the Claisen-Ireland rearrangement. Aryl residues have been introduced to fill the enzyme's P1' specificity pocket. The best compound inhibits MMPs and TACE with nanomolar potency and inhibits the release of TNFalpha from cells with an IC50 of 48 nM. Oral administration to rats inhibits the LPS-induced plasma TNFa levels with an ED50 of 1 mg/kg.

  DOI：

  10.1021/jm0110993

文献信息

• β-Aryl-Succinic Acid Hydroxamates as Dual Inhibitors of Matrix Metalloproteinases and Tumor Necrosis Factor Alpha Converting Enzyme
  作者：Georg Kottirsch、Guido Koch、Roland Feifel、Ulf Neumann

  DOI：10.1021/jm0110993

  日期：2002.5.1

  Novel hydroxamate inhibitors of tumor necrosis factor converting enzyme (TACE) and matrix metalloproteases (MMPs) have been synthesized via the Claisen-Ireland rearrangement. Aryl residues have been introduced to fill the enzyme's P1' specificity pocket. The best compound inhibits MMPs and TACE with nanomolar potency and inhibits the release of TNFalpha from cells with an IC50 of 48 nM. Oral administration to rats inhibits the LPS-induced plasma TNFa levels with an ED50 of 1 mg/kg.