methyl (3R)-3-[[(2S)-1-[[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]carbamoyl]-5-methylhexanoate | 200865-73-2

• 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: methyl (3R)-3-[[(2S)-1-[[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]carbamoyl]-5-methylhexanoate
• CAS: 200865-73-2
• 化学式: C₂₉H₃₅N₃O₅
• 分子量: 505.614
• InChiKey: CGGKRGOCZHBUDV-PBWWRKFESA-N

物化性质

• 沸点：
  818.206±65.00 °C(Press: 760.00 Torr)(predicted)
• 密度：
  1.265±0.10 g/cm3(Temp: 25 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  37
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  121
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl (3R)-3-[[(2S)-1-[[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]carbamoyl]-5-methylhexanoate 在 氢氧化钾 、 盐酸羟胺 作用下， 以 甲醇 为溶剂， 以20%的产率得到(2R)-N'-hydroxy-N-[(2S)-1-[[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]-2-(2-methylpropyl)butanediamide
  参考文献：
  名称：

  Matrix Metalloproteinase Inhibitors:  A Structure−Activity Study

  摘要：

  Modifications around the dipeptide-mimetic core of a hydroxamic acid based matrix metalloproteinase inhibitor were studied. These variations incorporated a variety of natural, unnatural, and synthetic amino acids in addition to modifications of the P1' and P3' substituents. The results of this study indicate the following structural requirements: (1) Two key hydrogen bonds must be present between the enzyme and potent substrates. (2) Potent inhibitors must possess strong zinc-binding functionalities. (3) The potential importance of the hydrophobic group at position R3 as illustrated by its ability to impart greater relative potency against stromelysin when larger hydrophobic groups are used. (4) Requirements surrounding the nature of the amino acid appear to be more restrictive for stromelysin than for neutrophil collagenase, 72 kDa gelatinase, and 92 kDa gelatinase. These requirements may involve planar fused-ring aryl systems and possibly hydrogen-bonding capabilities.

  DOI：

  10.1021/jm970494j
• 作为产物：
  描述：

  N-叔丁氧羰基-L-色氨酸 在 盐酸 、 三乙胺 、 N,N'-羰基二咪唑 作用下， 以 1,4-二氧六环 、 甲醇 为溶剂， 反应 32.0h， 生成 methyl (3R)-3-[[(2S)-1-[[(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]carbamoyl]-5-methylhexanoate
  参考文献：
  名称：

  Matrix Metalloproteinase Inhibitors:  A Structure−Activity Study

  摘要：

  Modifications around the dipeptide-mimetic core of a hydroxamic acid based matrix metalloproteinase inhibitor were studied. These variations incorporated a variety of natural, unnatural, and synthetic amino acids in addition to modifications of the P1' and P3' substituents. The results of this study indicate the following structural requirements: (1) Two key hydrogen bonds must be present between the enzyme and potent substrates. (2) Potent inhibitors must possess strong zinc-binding functionalities. (3) The potential importance of the hydrophobic group at position R3 as illustrated by its ability to impart greater relative potency against stromelysin when larger hydrophobic groups are used. (4) Requirements surrounding the nature of the amino acid appear to be more restrictive for stromelysin than for neutrophil collagenase, 72 kDa gelatinase, and 92 kDa gelatinase. These requirements may involve planar fused-ring aryl systems and possibly hydrogen-bonding capabilities.

  DOI：

  10.1021/jm970494j