[(2S)-2-(4-tert-butoxybenzyl)-9-[(9H-fluoren-9-ylmethoxycarbonyl)amino]-3-oxo-1,2,3,5-tetrahydrobenzo[1,4]diazepin-4-yl]acetic acid | 857040-93-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: [(2S)-2-(4-tert-butoxybenzyl)-9-[(9H-fluoren-9-ylmethoxycarbonyl)amino]-3-oxo-1,2,3,5-tetrahydrobenzo[1,4]diazepin-4-yl]acetic acid
• 英文别名: 2-[(2S)-9-(9H-fluoren-9-ylmethoxycarbonylamino)-2-[[4-[(2-methylpropan-2-yl)oxy]phenyl]methyl]-3-oxo-2,5-dihydro-1H-1,4-benzodiazepin-4-yl]acetic acid
• CAS: 857040-93-8
• 化学式: C₃₇H₃₇N₃O₆
• 分子量: 619.717
• InChiKey: GXQPGLOLHHMKSK-YTTGMZPUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  46
• 可旋转键数：
  10
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  117
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  [(2S)-2-(4-tert-butoxybenzyl)-9-[(9H-fluoren-9-ylmethoxycarbonyl)amino]-3-oxo-1,2,3,5-tetrahydrobenzo[1,4]diazepin-4-yl]acetic acid 、 Fmoc-L-缬氨酸 、 Fmoc-L-丙氨酸 、 Fmoc-L-天冬氨酸 beta-叔丁酯 、 alkaline earth salt of/the/ methylsulfuric acid 以35.8%的产率得到(3S)-3-amino-3-{[(1S)-1-{[(1S)-1-{[(2S)-4-({[(2S)-1-[(2S)-2-{[(1S)-1-carboxy-2-phenylethyl]carbamoyl}pyrrolidin-1-yl]-3-(1H-imidazol-4-yl)-1-oxopropan-2-yl]carbamoyl}methyl)-2-[(4-hydroxyphenyl)methyl]-3-oxo-2,3,4,5-tetrahydro-1H-1,4-benzodiazepin-9-yl]carbamoyl}-2-methylpropyl]carbamoyl}ethyl]carbamoyl}propanoic acid
  参考文献：
  名称：

  New Selective AT₂ Receptor Ligands Encompassing a γ-Turn Mimetic Replacing the Amino Acid Residues 4−5 of Angiotensin II Act as Agonists

  摘要：

  New benzodiazepine-based gamma-turn mimetics with one or two amino acid side chains were synthesized. The gamma-turn mimetics were incorporated into angiotensin II (Ang II) replacing the Val(3)-Tyr(4)-Ile(5) or Tyr(4)-Ile(5) peptide segments. All of the resulting pseudopeptides displayed high AT(2)/AT(1) receptor selectivity and exhibited AT(2) receptor affinity in the low nanomolar range. Molecular modeling was used to investigate whether the compounds binding to the AT(2) receptor could position important structural elements in common areas. A previously described benzodiazepine-based gamma-turn mimetic with high affinity for the AT(2) receptor was also included in the modeling. It was found that the molecules, although being structurally quite different, could adopt the same binding mode/interaction pattern in agreement with the model hypothesis. The pseudopeptides selected for agonist studies were shown to act as AT(2) receptor agonists being able to induce outgrowth of neurite cells, stimulate p42/p44(mapk), and suppress proliferation of PC12 cells.

  DOI：

  10.1021/jm0491492
• 作为产物：
  描述：

  、 氯甲酸-9-芴基甲酯 在 sodium carbonate 作用下， 以 1,4-二氧六环 为溶剂， 反应 48.0h， 生成 [(2S)-2-(4-tert-butoxybenzyl)-9-[(9H-fluoren-9-ylmethoxycarbonyl)amino]-3-oxo-1,2,3,5-tetrahydrobenzo[1,4]diazepin-4-yl]acetic acid
  参考文献：
  名称：

  New Selective AT₂ Receptor Ligands Encompassing a γ-Turn Mimetic Replacing the Amino Acid Residues 4−5 of Angiotensin II Act as Agonists

  摘要：

  New benzodiazepine-based gamma-turn mimetics with one or two amino acid side chains were synthesized. The gamma-turn mimetics were incorporated into angiotensin II (Ang II) replacing the Val(3)-Tyr(4)-Ile(5) or Tyr(4)-Ile(5) peptide segments. All of the resulting pseudopeptides displayed high AT(2)/AT(1) receptor selectivity and exhibited AT(2) receptor affinity in the low nanomolar range. Molecular modeling was used to investigate whether the compounds binding to the AT(2) receptor could position important structural elements in common areas. A previously described benzodiazepine-based gamma-turn mimetic with high affinity for the AT(2) receptor was also included in the modeling. It was found that the molecules, although being structurally quite different, could adopt the same binding mode/interaction pattern in agreement with the model hypothesis. The pseudopeptides selected for agonist studies were shown to act as AT(2) receptor agonists being able to induce outgrowth of neurite cells, stimulate p42/p44(mapk), and suppress proliferation of PC12 cells.

  DOI：

  10.1021/jm0491492