diphenyl (N-benzyloxycarbonyl-L-alanyl)amino-(4-(N,N'-bis(tert-butyloxycarbonyl)guanyl)phenyl)methanephosphonate | 695172-08-8

• 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: diphenyl (N-benzyloxycarbonyl-L-alanyl)amino-(4-(N,N'-bis(tert-butyloxycarbonyl)guanyl)phenyl)methanephosphonate
• CAS: 695172-08-8
• 化学式: C₄₁H₄₈N₅O₁₀P
• 分子量: 801.833
• InChiKey: VRHWBUMUFLHICJ-GYKKGXIBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.7
• 重原子数：
  57.0
• 可旋转键数：
  12.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  191.98
• 氢给体数：
  4.0
• 氢受体数：
  10.0

反应信息

• 作为反应物：
  描述：

  diphenyl (N-benzyloxycarbonyl-L-alanyl)amino-(4-(N,N'-bis(tert-butyloxycarbonyl)guanyl)phenyl)methanephosphonate 在 palladium on activated charcoal TEA 、 氢气 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 三氟乙酸 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 11.17h， 生成 diphenyl ((N-benzyloxycarbonyl-D-seryl)-L-alanyl)amino-(4-guanylphenyl)methanephosphonate trifluoroacetate
  参考文献：
  名称：

  Development of Irreversible Diphenyl Phosphonate Inhibitors for Urokinase Plasminogen Activator

  摘要：

  In this letter we report the synthesis and biochemical evaluation of selective, irreversible diphenyl phosphonate inhibitors for urokinase plasminogen activator (uPA). A diphenyl phosphonate group was introduced on the substratelike peptide Z-D-Ser-Ala-Arg, and modification of the guanidine side chain was investigated. A guanylated benzyl group appeared the most promising side chain modification. A k(app) value in the 10(3) M-1 s(-1) range for uPA was obtained, together with a selectivity index higher than 240 toward other trypsin-like proteases such as tPA, thrombin, plasmin, and FXa.

  DOI：

  10.1021/jm0499209
• 作为产物：
  描述：

  N,N'-bis( tert-butoxycarbonyl)-1H-pyrazole-1-carboxamidine 在 palladium on activated charcoal TEA 、 氢气 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 8.17h， 生成 diphenyl (N-benzyloxycarbonyl-L-alanyl)amino-(4-(N,N'-bis(tert-butyloxycarbonyl)guanyl)phenyl)methanephosphonate
  参考文献：
  名称：

  Development of Irreversible Diphenyl Phosphonate Inhibitors for Urokinase Plasminogen Activator

  摘要：

  In this letter we report the synthesis and biochemical evaluation of selective, irreversible diphenyl phosphonate inhibitors for urokinase plasminogen activator (uPA). A diphenyl phosphonate group was introduced on the substratelike peptide Z-D-Ser-Ala-Arg, and modification of the guanidine side chain was investigated. A guanylated benzyl group appeared the most promising side chain modification. A k(app) value in the 10(3) M-1 s(-1) range for uPA was obtained, together with a selectivity index higher than 240 toward other trypsin-like proteases such as tPA, thrombin, plasmin, and FXa.

  DOI：

  10.1021/jm0499209