benzyl N-[(4S)-6-amino-4-[(2-methylpropan-2-yl)oxycarbonylamino]-5-oxohexyl]-N-[(E)-N'-phenylmethoxycarbonylcarbamimidoyl]carbamate | 244192-67-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: benzyl N-[(4S)-6-amino-4-[(2-methylpropan-2-yl)oxycarbonylamino]-5-oxohexyl]-N-[(E)-N'-phenylmethoxycarbonylcarbamimidoyl]carbamate
• CAS: 244192-67-4
• 化学式: C₂₈H₃₇N₅O₇
• 分子量: 555.631
• InChiKey: OACDPXUZAFUCHT-QFIPXVFZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  40
• 可旋转键数：
  16
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  176
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  丁二酸酐 、 benzyl N-[(4S)-6-amino-4-[(2-methylpropan-2-yl)oxycarbonylamino]-5-oxohexyl]-N-[(E)-N'-phenylmethoxycarbonylcarbamimidoyl]carbamate 在 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 24.0h， 生成 Boc-Arg(Z)2ΨGly-OH
  参考文献：
  名称：

  Potent Bivalent Thrombin Inhibitors:  Replacement of the Scissile Peptide Bond at P₁−P₁‘ with Arginyl Ketomethylene Isosteres

  摘要：

  We have designed highly potent synthetic bivalent thrombin inhibitors, which consist of an active site blocking segment, a fibrinogen recognition exosite blocking segment, and a linker connecting these segments. The bivalent inhibitors bind to the active site and the fibrinogen recognition exosite simultaneously. As a result, the inhibitors showed much higher affinity for thrombin than the individual blocking segments. Various arginyl ketomethylene isosteres Arg Psi-[CO-CH2-X]P-1' were incorporated into the bivalent inhibitors as P-1-P-1' segment to eliminate the scissile bond. The P-1' residue is a natural or unnatural amino acid; specifically, the incorporation of mercaptoacetic acid exhibited superiority in synthesis and affinity for thrombin. Inhibitor 16, (D-cyclohexylalanine)-Pro-Arg Psi[CO-CH2-S]Gly-(Gly)(4)-Asp-Tyr-Glu-Pro-Ile-Pro-Glu-Glu-Tyr-cyclohexylalanine-(D-Glu)-OH showed the lowest K-i value of 3.5 +/- 0.5 x 10(-13) M, which is comparable to that (K-i = 2.3 x 10(-13) M) of recombinant hirudin. Consequently we successfully reduced the size of the inhibitor from similar to 7 kDa of recombinant hirudin to similar to 2 kDa without losing the affinity.

  DOI：

  10.1021/jm9807297
• 作为产物：
  描述：

  benzyl N-[(4S)-6-diazo-4-[(2-methylpropan-2-yl)oxycarbonylamino]-5-oxohexyl]-N-[(E)-N'-phenylmethoxycarbonylcarbamimidoyl]carbamate 在 盐酸 、 氨 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 乙醚 为溶剂， 反应 72.17h， 生成 benzyl N-[(4S)-6-amino-4-[(2-methylpropan-2-yl)oxycarbonylamino]-5-oxohexyl]-N-[(E)-N'-phenylmethoxycarbonylcarbamimidoyl]carbamate
  参考文献：
  名称：

  Potent Bivalent Thrombin Inhibitors:  Replacement of the Scissile Peptide Bond at P₁−P₁‘ with Arginyl Ketomethylene Isosteres

  摘要：

  We have designed highly potent synthetic bivalent thrombin inhibitors, which consist of an active site blocking segment, a fibrinogen recognition exosite blocking segment, and a linker connecting these segments. The bivalent inhibitors bind to the active site and the fibrinogen recognition exosite simultaneously. As a result, the inhibitors showed much higher affinity for thrombin than the individual blocking segments. Various arginyl ketomethylene isosteres Arg Psi-[CO-CH2-X]P-1' were incorporated into the bivalent inhibitors as P-1-P-1' segment to eliminate the scissile bond. The P-1' residue is a natural or unnatural amino acid; specifically, the incorporation of mercaptoacetic acid exhibited superiority in synthesis and affinity for thrombin. Inhibitor 16, (D-cyclohexylalanine)-Pro-Arg Psi[CO-CH2-S]Gly-(Gly)(4)-Asp-Tyr-Glu-Pro-Ile-Pro-Glu-Glu-Tyr-cyclohexylalanine-(D-Glu)-OH showed the lowest K-i value of 3.5 +/- 0.5 x 10(-13) M, which is comparable to that (K-i = 2.3 x 10(-13) M) of recombinant hirudin. Consequently we successfully reduced the size of the inhibitor from similar to 7 kDa of recombinant hirudin to similar to 2 kDa without losing the affinity.

  DOI：

  10.1021/jm9807297