(2R,3R)-N4-Benzyloxy-2-isobutyl-N1-((S)-methylcarbamoyl-phenyl-methyl)-3-morpholin-4-ylmethyl-succinamide | 168158-24-5

• 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: (2R,3R)-N4-Benzyloxy-2-isobutyl-N1-((S)-methylcarbamoyl-phenyl-methyl)-3-morpholin-4-ylmethyl-succinamide
• CAS: 168158-24-5
• 化学式: C₂₉H₄₀N₄O₅
• 分子量: 524.66
• InChiKey: VDMGHGLGHYUWDP-ZNZIZOMTSA-N

物化性质

• 密度：
  1.152±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.45
• 重原子数：
  38.0
• 可旋转键数：
  13.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  109.0
• 氢给体数：
  3.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  (2R,3R)-N4-Benzyloxy-2-isobutyl-N1-((S)-methylcarbamoyl-phenyl-methyl)-3-morpholin-4-ylmethyl-succinamide 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 为溶剂， 以85.8%的产率得到(2R,3R)-N-hydroxy-N'-[(1S)-2-(methylamino)-2-oxo-1-phenylethyl]-3-(2-methylpropyl)-2-(morpholin-4-ylmethyl)butanediamide
  参考文献：
  名称：

  Synthesis and biological evaluation of orally active matrix metalloproteinase inhibitors

  摘要：

  The synthesis and biological evaluation of orally active inhibitors of matrix metalloproteinase are reported. Modifications of the P2' position and the a-substituent of hydroxamic acid derivatives were carried out, and revealed that the P2' substituent influenced the MMP inhibitory activities in vitro and in plasma after oral administration. The hydroxamates with phenylglycine at the P2' position were absorbed well orally. Compound 15e, which exhibited the longest duration of inhibitory activity in plasma after oral administration among the phenylglycine derivatives (5a-5d, 15a, 15c, 15e), was evaluated in a rat adjuvant arthritis model. A reduction in hind foot pad swelling and improvements of some inflammatory parameters were demonstrated when the compound was administered orally. These results indicate the potential of MMP inhibitors for rheumatoid arthritis. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0968-0896(97)00028-x
• 作为产物：
  描述：

  (R)-2-溴-4-甲基戊酸叔丁酯 在 palladium on activated charcoal 哌啶 、 N-甲基吗啉 、 4-氨基吡啶 、 potassium tert-butylate 、 ammonium formate 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 144.0h， 生成 (2R,3R)-N4-Benzyloxy-2-isobutyl-N1-((S)-methylcarbamoyl-phenyl-methyl)-3-morpholin-4-ylmethyl-succinamide
  参考文献：
  名称：

  Synthesis and biological evaluation of orally active matrix metalloproteinase inhibitors

  摘要：

  The synthesis and biological evaluation of orally active inhibitors of matrix metalloproteinase are reported. Modifications of the P2' position and the a-substituent of hydroxamic acid derivatives were carried out, and revealed that the P2' substituent influenced the MMP inhibitory activities in vitro and in plasma after oral administration. The hydroxamates with phenylglycine at the P2' position were absorbed well orally. Compound 15e, which exhibited the longest duration of inhibitory activity in plasma after oral administration among the phenylglycine derivatives (5a-5d, 15a, 15c, 15e), was evaluated in a rat adjuvant arthritis model. A reduction in hind foot pad swelling and improvements of some inflammatory parameters were demonstrated when the compound was administered orally. These results indicate the potential of MMP inhibitors for rheumatoid arthritis. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0968-0896(97)00028-x