ethyl (4S)-6-(benzyloxycarbonyl)amino-4-(tert-butoxycarbonyl)amino-3-oxohexanoate | 383174-71-8

• 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: ethyl (4S)-6-(benzyloxycarbonyl)amino-4-(tert-butoxycarbonyl)amino-3-oxohexanoate
• 英文别名: ethyl (4S)-4-[(2-methylpropan-2-yl)oxycarbonylamino]-3-oxo-6-(phenylmethoxycarbonylamino)hexanoate
• CAS: 383174-71-8
• 化学式: C₂₁H₃₀N₂O₇
• 分子量: 422.478
• InChiKey: RHJFUVGJDQMGQB-INIZCTEOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  30
• 可旋转键数：
  14
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  120
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  ethyl (4S)-6-(benzyloxycarbonyl)amino-4-(tert-butoxycarbonyl)amino-3-oxohexanoate 在 10percent Pd/C 氢气 、 sodium cyanoborohydride 、 zinc(II) chloride 作用下， 以 乙醇 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 49.0h， 生成 2,3-trans-3-(tert-butoxycarbonyl)amino-2-(ethoxycarbonyl)methylpyrrolidine 、 2,3-cis-3-(tert-butoxycarbonyl)amino-2-(ethoxycarbonyl)methylpyrrolidine
  参考文献：
  名称：

  5-(Tryptophyl)amino-1,3-dioxoperhydropyrido[1,2-c]pyrimidine-Based Potent and Selective CCK₁ Receptor Antagonists:  Structure−Activity Relationship Studies on the Central 1,3-Dioxoperhydropyrido[1,2-c]pyrimidine Scaffold

  摘要：

  To further define the pharmacophore of the potent and selective 5-(tryptophyl)amino-1,3-dioxoperhydropyrido[1,2-c]pyrimidine-based CCK1 receptor antagonists the electronic and topographic properties of the central 1, 3-dioxoperhydro-pyrido[1,2-c]pyrimidine scaffold have been modified. With this aim, the 1- and 3-oxo groups have been replaced by the thioxo- and deoxi-analogues, and the fused piperidine ring has been contracted to the corresponding pyrrolidine moiety. The results of the evaluation of the new analogues as CCK receptor ligands, in rat pancreas and cerebral cortex preparations, showed that, whereas replacement of oxygen with sulfur is allowed, reduction of the 1- or 3-oxo groups or the contraction of the fused piperidine ring lead to the complete loss of binding affinity at CCK1 receptors. The thioxo-analogues 5a, 8a, 12a, and 12b showed functional CCK1 antagonist activity, inhibiting the CCK-8-stimulated amylase release from pancreatic acinar cells. The 1-thioxo analogue 5a, with subnanomolar affinity (IC50 = 0.09 x 10(-9) M), was found to be the most potent and selective compound within the family of 5-(tryptophyl)amino-1,3-dioxoperhydropyrido[1,2-c]pyrimidine-based CCK1 antagonists.

  DOI：

  10.1021/jm010898i
• 作为产物：
  描述：

  ethyl lithioacetate 、 (2S)-4-(benzyloxycarbonyl)amino-2-(tert-butoxycarbonyl)aminobutyric acid 在 N,N'-羰基二咪唑 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 0.58h， 以45%的产率得到ethyl (4S)-6-(benzyloxycarbonyl)amino-4-(tert-butoxycarbonyl)amino-3-oxohexanoate
  参考文献：
  名称：

  5-(Tryptophyl)amino-1,3-dioxoperhydropyrido[1,2-c]pyrimidine-Based Potent and Selective CCK₁ Receptor Antagonists:  Structure−Activity Relationship Studies on the Central 1,3-Dioxoperhydropyrido[1,2-c]pyrimidine Scaffold

  摘要：

  To further define the pharmacophore of the potent and selective 5-(tryptophyl)amino-1,3-dioxoperhydropyrido[1,2-c]pyrimidine-based CCK1 receptor antagonists the electronic and topographic properties of the central 1, 3-dioxoperhydro-pyrido[1,2-c]pyrimidine scaffold have been modified. With this aim, the 1- and 3-oxo groups have been replaced by the thioxo- and deoxi-analogues, and the fused piperidine ring has been contracted to the corresponding pyrrolidine moiety. The results of the evaluation of the new analogues as CCK receptor ligands, in rat pancreas and cerebral cortex preparations, showed that, whereas replacement of oxygen with sulfur is allowed, reduction of the 1- or 3-oxo groups or the contraction of the fused piperidine ring lead to the complete loss of binding affinity at CCK1 receptors. The thioxo-analogues 5a, 8a, 12a, and 12b showed functional CCK1 antagonist activity, inhibiting the CCK-8-stimulated amylase release from pancreatic acinar cells. The 1-thioxo analogue 5a, with subnanomolar affinity (IC50 = 0.09 x 10(-9) M), was found to be the most potent and selective compound within the family of 5-(tryptophyl)amino-1,3-dioxoperhydropyrido[1,2-c]pyrimidine-based CCK1 antagonists.

  DOI：

  10.1021/jm010898i