(2S,3S)-2-[[2-[hydroxy(methyl)amino]-3,4-dioxocyclobuten-1-yl]amino]-3-methyl-N-[(2S)-1-(methylamino)-1-oxo-3-phenylpropan-2-yl]pentanamide | 871917-55-4

• 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: (2S,3S)-2-[[2-[hydroxy(methyl)amino]-3,4-dioxocyclobuten-1-yl]amino]-3-methyl-N-[(2S)-1-(methylamino)-1-oxo-3-phenylpropan-2-yl]pentanamide
• CAS: 871917-55-4
• 化学式: C₂₁H₂₈N₄O₅
• 分子量: 416.477
• InChiKey: BUWQGRFJDHFYEE-QEJZJMRPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  30
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  128
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (2S,3S)-2-[[2-[hydroxy(methyl)amino]-3,4-dioxocyclobuten-1-yl]amino]-3-methyl-N-[(2S)-1-(methylamino)-1-oxo-3-phenylpropan-2-yl]pentanamide 在 劳森试剂 作用下， 以 二氯甲烷 为溶剂， 以71%的产率得到(2S,3S)-2-[[2-[hydroxy(methyl)amino]-4-oxo-3-sulfanylidenecyclobuten-1-yl]amino]-3-methyl-N-[(2S)-1-(methylamino)-1-oxo-3-phenylpropan-2-yl]pentanamide
  参考文献：
  名称：

  Squaric Acid-Based Peptidic Inhibitors of Matrix Metalloprotease-1

  摘要：

  A series of squaric acid-peptide conjugates were synthesized and evaluated as inhibitors of MMP-1. The cyclobut-3-enedione core was substituted at the 3-position with several functional groups, such as -N(alkyl)OH, -NHOH, and -OH, that are designed to bind to the zinc atom in the active site of the metalloprotease. The 4-position of the cyclobut-3-enedione was derivatized with mono- or dipeptides that are designed to bind in the S1' and S2' subsites of the enzyme, and position the metal chelating group appropriately in the active site for binding to zinc. Positional scanning revealed that -N(Me)OH provided the highest level of inhibition among the chelating groups that were tested, and Leu-Tle-NHMe was the preferred amino acid sequence. A combination of these groups yielded an inhibitor with an IC50 value of 95 mu M. For one inhibitor, conversion of one of the carbonyl groups on the cyclobut-3-enedione core to a thiocarbonyl group resulted in a 18-fold increase in potency, and yielded a compound with an IC50 value of 15 mu M.

  DOI：

  10.1021/jo0517848
• 作为产物：
  描述：

  L-苯基丙氨酸甲酰胺 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三氟乙酸 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 1.17h， 生成 (2S,3S)-2-[[2-[hydroxy(methyl)amino]-3,4-dioxocyclobuten-1-yl]amino]-3-methyl-N-[(2S)-1-(methylamino)-1-oxo-3-phenylpropan-2-yl]pentanamide
  参考文献：
  名称：

  Squaric Acid-Based Peptidic Inhibitors of Matrix Metalloprotease-1

  摘要：

  A series of squaric acid-peptide conjugates were synthesized and evaluated as inhibitors of MMP-1. The cyclobut-3-enedione core was substituted at the 3-position with several functional groups, such as -N(alkyl)OH, -NHOH, and -OH, that are designed to bind to the zinc atom in the active site of the metalloprotease. The 4-position of the cyclobut-3-enedione was derivatized with mono- or dipeptides that are designed to bind in the S1' and S2' subsites of the enzyme, and position the metal chelating group appropriately in the active site for binding to zinc. Positional scanning revealed that -N(Me)OH provided the highest level of inhibition among the chelating groups that were tested, and Leu-Tle-NHMe was the preferred amino acid sequence. A combination of these groups yielded an inhibitor with an IC50 value of 95 mu M. For one inhibitor, conversion of one of the carbonyl groups on the cyclobut-3-enedione core to a thiocarbonyl group resulted in a 18-fold increase in potency, and yielded a compound with an IC50 value of 15 mu M.

  DOI：

  10.1021/jo0517848