benzyl N-[(5S)-6-[1-bis(4-acetamidophenoxy)phosphoryl-1,3-dihydroisoindol-2-yl]-5-[(2-methylpropan-2-yl)oxycarbonylamino]-6-oxohexyl]carbamate | 960300-36-1

• 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: benzyl N-[(5S)-6-[1-bis(4-acetamidophenoxy)phosphoryl-1,3-dihydroisoindol-2-yl]-5-[(2-methylpropan-2-yl)oxycarbonylamino]-6-oxohexyl]carbamate
• CAS: 960300-36-1
• 化学式: C₄₃H₅₀N₅O₁₀P
• 分子量: 827.871
• InChiKey: WJLBZHSJBKGNOQ-VBXQXZIHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  59
• 可旋转键数：
  19
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  191
• 氢给体数：
  4
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  benzyl N-[(5S)-6-[1-bis(4-acetamidophenoxy)phosphoryl-1,3-dihydroisoindol-2-yl]-5-[(2-methylpropan-2-yl)oxycarbonylamino]-6-oxohexyl]carbamate 、 三氟乙酸 以 二氯甲烷 为溶剂， 反应 0.33h， 以99%的产率得到benzyl (S)-5-amino-6-(1-(di-(4-acetamido)phenoxyphosphoryl)isoindolin-2-yl)-6-oxohexylcarbamate trifluoroacetate
  参考文献：
  名称：

  Irreversible Inhibition of Dipeptidyl Peptidase 8 by Dipeptide-Derived Diaryl Phosphonates

  摘要：

  Dipeptide-derived compounds, bearing various P2 residues and a diaryl pyrrolidin-2-yl phosphonate at the PI position, were evaluated as dipeptidyl peptidase 8 (DPP8) inhibitors. With these products, irreversible inhibition of DPP8 was observed. To obtain inhibitors with an improved activity and selectivity profile, a set of selected analogues containing a diaryl isoindolin-1-ylphosphonate at P1 was synthesized and evaluated. Within this latter series, compound 2e was shown to be a potent, irreversible inhibitor of DPP8, demonstrating very low affinity for DPP IV and DPP II.

  DOI：

  10.1021/jm701005a
• 作为产物：
  描述：

  tert-butyl (S)-6-(N-benzyloxycarbonyl)amino-1-(1-hydroxyisoindolin-2-yl)-1-oxohexan-2-ylcarbamate 、 tris(4-acetamidophenyl) phosphite 在 三氟化硼乙醚 作用下， 以 乙腈 为溶剂， 反应 2.0h， 生成 benzyl N-[(5S)-6-[1-bis(4-acetamidophenoxy)phosphoryl-1,3-dihydroisoindol-2-yl]-5-[(2-methylpropan-2-yl)oxycarbonylamino]-6-oxohexyl]carbamate
  参考文献：
  名称：

  Irreversible Inhibition of Dipeptidyl Peptidase 8 by Dipeptide-Derived Diaryl Phosphonates

  摘要：

  Dipeptide-derived compounds, bearing various P2 residues and a diaryl pyrrolidin-2-yl phosphonate at the PI position, were evaluated as dipeptidyl peptidase 8 (DPP8) inhibitors. With these products, irreversible inhibition of DPP8 was observed. To obtain inhibitors with an improved activity and selectivity profile, a set of selected analogues containing a diaryl isoindolin-1-ylphosphonate at P1 was synthesized and evaluated. Within this latter series, compound 2e was shown to be a potent, irreversible inhibitor of DPP8, demonstrating very low affinity for DPP IV and DPP II.

  DOI：

  10.1021/jm701005a

文献信息

• Irreversible Inhibition of Dipeptidyl Peptidase 8 by Dipeptide-Derived Diaryl Phosphonates
  作者：Pieter Van der Veken、Anna Soroka、Inger Brandt、Yuan-Shou Chen、Marie-Berthe Maes、Anne-Marie Lambeir、Xin Chen、Achiel Haemers、Simon Scharpé、Koen Augustyns、Ingrid De Meester

  DOI：10.1021/jm701005a

  日期：2007.11.1

  Dipeptide-derived compounds, bearing various P2 residues and a diaryl pyrrolidin-2-yl phosphonate at the PI position, were evaluated as dipeptidyl peptidase 8 (DPP8) inhibitors. With these products, irreversible inhibition of DPP8 was observed. To obtain inhibitors with an improved activity and selectivity profile, a set of selected analogues containing a diaryl isoindolin-1-ylphosphonate at P1 was synthesized and evaluated. Within this latter series, compound 2e was shown to be a potent, irreversible inhibitor of DPP8, demonstrating very low affinity for DPP IV and DPP II.