{(S)-2-(4-tert-Butoxy-phenyl)-1-[(2-chloro-3-nitro-benzyl)-((1S,2S)-1-hydroxymethyl-2-methyl-butyl)-carbamoyl]-ethyl}-carbamic acid 9H-fluoren-9-ylmethyl ester | 866552-89-8

• 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: {(S)-2-(4-tert-Butoxy-phenyl)-1-[(2-chloro-3-nitro-benzyl)-((1S,2S)-1-hydroxymethyl-2-methyl-butyl)-carbamoyl]-ethyl}-carbamic acid 9H-fluoren-9-ylmethyl ester
• CAS: 866552-89-8
• 化学式: C₄₁H₄₆ClN₃O₇
• 分子量: 728.285
• InChiKey: UMJRDUVFGSLQQF-IZWJPAILSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.31
• 重原子数：
  52.0
• 可旋转键数：
  14.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  131.24
• 氢给体数：
  2.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  {(S)-2-(4-tert-Butoxy-phenyl)-1-[(2-chloro-3-nitro-benzyl)-((1S,2S)-1-hydroxymethyl-2-methyl-butyl)-carbamoyl]-ethyl}-carbamic acid 9H-fluoren-9-ylmethyl ester 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三乙胺 作用下， 以 四氢呋喃 、 二甲基亚砜 为溶剂， 反应 26.0h， 生成 (2S)-2-(4-tert-butoxybenzyl)-4-[(1S,2S)-(1-hydroxymethyl-2-methyl-butyl)]-9-nitro-1,2,4,5-tetrahydrobenzo[1,4]diazepin-3-one
  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：

  2-氯-3-硝基苯甲酸 在 sodium tetrahydroborate 、 草酰氯 、 三氟化硼乙醚 、 sodium cyanoborohydride 、 溶剂黄146 、 二甲基亚砜 、 三乙胺 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 5.25h， 生成 {(S)-2-(4-tert-Butoxy-phenyl)-1-[(2-chloro-3-nitro-benzyl)-((1S,2S)-1-hydroxymethyl-2-methyl-butyl)-carbamoyl]-ethyl}-carbamic acid 9H-fluoren-9-ylmethyl ester
  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