(S)-1-((S)-4-Carbamoyl-2-{[(S)-1-((S)-4-carbamoyl-2-{2-[(9,10-dioxo-9,10-dihydro-phenanthrene-3-carbonyl)-amino]-acetylamino}-butyryl)-pyrrolidine-2-carbonyl]-amino}-butyryl)-pyrrolidine-2-carboxylic acid

• 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: (S)-1-((S)-4-Carbamoyl-2-{[(S)-1-((S)-4-carbamoyl-2-{2-[(9,10-dioxo-9,10-dihydro-phenanthrene-3-carbonyl)-amino]-acetylamino}-butyryl)-pyrrolidine-2-carbonyl]-amino}-butyryl)-pyrrolidine-2-carboxylic acid
• 英文别名: (2S)-1-[(2S)-5-amino-2-[[(2S)-1-[(2S)-5-amino-2-[[2-[(9,10-dioxophenanthrene-3-carbonyl)amino]acetyl]amino]-5-oxopentanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]pyrrolidine-2-carboxylic acid
• 化学式: C₃₇H₄₁N₇O₁₁
• 分子量: 759.773
• InChiKey: AWTUWVXFKPDVME-FWEHEUNISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.2
• 重原子数：
  55
• 可旋转键数：
  15
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  286
• 氢给体数：
  6
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  Fmoc-甘氨酸 、 phenanthrenequinone-3-carboxylic acid 、 Fmoc-L-脯氨酸 、 Fmoc-N-三苯甲基-L-谷氨酰胺 生成 (S)-1-((S)-4-Carbamoyl-2-{[(S)-1-((S)-4-carbamoyl-2-{2-[(9,10-dioxo-9,10-dihydro-phenanthrene-3-carbonyl)-amino]-acetylamino}-butyryl)-pyrrolidine-2-carbonyl]-amino}-butyryl)-pyrrolidine-2-carboxylic acid
  参考文献：
  名称：

  Potent Reversible Inhibitors of the Protein Tyrosine Phosphatase CD45

  摘要：

  The cytosolic portion of CD45, a major transmembrane glycoprotein found on nucleated hematopoietic cells, contains protein tyrosine phosphatase activity and is critical for T-cell receptor-mediated T-cell activation. CD45 inhibitors could have utility in the treatment of autoimmune disorders and organ graft rejection. A number of 9, l0-phenanthrenediones were identified that reversibly inhibited CD45-mediated p-nitrophenyl phosphate (pNPP) hydrolysis. Chemistry efforts around the 9,10-phenanthrenedione core led to the most potent inhibitors known to date. In a functional assay, the compounds were also potent inhibitors of T-cell receptor-mediated proliferation, with activities in the low micromolar range paralleling their enzyme inhibition. It was also discovered that the nature of modification to the phenanthrenedione pharmacophore could affect selectivity for CD45 over PTP1B (protein tyrosine phosphatase 1B) or vice versa.

  DOI：

  10.1021/jm000447i

文献信息

• Potent Reversible Inhibitors of the Protein Tyrosine Phosphatase CD45
  作者：Rebecca A. Urbanek、Suzanne J. Suchard、Gary B. Steelman、Katharine S. Knappenberger、Linda A. Sygowski、Chris A. Veale、Marc J. Chapdelaine

  DOI：10.1021/jm000447i

  日期：2001.5.1

  The cytosolic portion of CD45, a major transmembrane glycoprotein found on nucleated hematopoietic cells, contains protein tyrosine phosphatase activity and is critical for T-cell receptor-mediated T-cell activation. CD45 inhibitors could have utility in the treatment of autoimmune disorders and organ graft rejection. A number of 9, l0-phenanthrenediones were identified that reversibly inhibited CD45-mediated p-nitrophenyl phosphate (pNPP) hydrolysis. Chemistry efforts around the 9,10-phenanthrenedione core led to the most potent inhibitors known to date. In a functional assay, the compounds were also potent inhibitors of T-cell receptor-mediated proliferation, with activities in the low micromolar range paralleling their enzyme inhibition. It was also discovered that the nature of modification to the phenanthrenedione pharmacophore could affect selectivity for CD45 over PTP1B (protein tyrosine phosphatase 1B) or vice versa.