4-{(E)-5-[4-((S)-2-Hexanoylamino-2-methoxycarbonyl-ethyl)-phenyl]-pent-2-en-4-ynyl}-piperidine-1-carboxylic acid tert-butyl ester | 142374-22-9

• 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: 4-{(E)-5-[4-((S)-2-Hexanoylamino-2-methoxycarbonyl-ethyl)-phenyl]-pent-2-en-4-ynyl}-piperidine-1-carboxylic acid tert-butyl ester
• CAS: 142374-22-9
• 化学式: C₃₁H₄₄N₂O₅
• 分子量: 524.701
• InChiKey: UJEHBPQEZCOQOS-MHZLTWQESA-N

物化性质

• 沸点：
  657.0±55.0 °C(Predicted)
• 密度：
  1.11±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.41
• 重原子数：
  38.0
• 可旋转键数：
  10.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  84.94
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  4-{(E)-5-[4-((S)-2-Hexanoylamino-2-methoxycarbonyl-ethyl)-phenyl]-pent-2-en-4-ynyl}-piperidine-1-carboxylic acid tert-butyl ester 在 palladium on activated charcoal 氢气 、 溶剂黄146 作用下， 以 乙醇 为溶剂， 反应 4.0h， 以79%的产率得到tert-butyl 4-[5-[4-[(2S)-2-(hexanoylamino)-3-methoxy-3-oxopropyl]phenyl]pentyl]piperidine-1-carboxylate
  参考文献：
  名称：

  Non-Peptide Fibrinogen Receptor Antagonists. 2. Optimization of a Tyrosine Template as a Mimic for Arg-Gly-Asp

  摘要：

  Inhibitors of platelet-fibrinogen binding offer an opportunity to interrupt the final, common pathway for platelet aggregation. Small molecule inhibitors of the platelet fibrinogen receptor GPIIb/IIIa were prepared and evaluated for their ability to prevent platelet aggregation. Compound 23m (L-700,462/MK-383) inhibited in vitro platelet aggregation with an IC50 of 9 nM and demonstrated a selectivity of > 24 000-fold between platelet and human umbilical vein endothelial cell fibrinogen receptors. Dose-dependent inhibition of ex vivo platelet aggregation induced by ADP was achieved with iv infusions of 0.1-10 mu g/kg/min of 23m in anesthetized dogs, with 10 mu g/kg/min completely inhibiting platelet aggregation during the entire 6 h infusion protocol. Platelet aggregatability returned rapidly after the termination of the 23m infusions. These features suggest that 23m may be useful in the treatment of arterial occlusive disorders.

  DOI：

  10.1021/jm00042a007
• 作为产物：
  描述：

  N-Boc-4-哌啶乙醇 在 bis-triphenylphosphine-palladium(II) chloride 、 lithium hydroxide 、 copper(l) iodide 、 正丁基锂 、 草酰氯 、 二甲基亚砜 、 二乙胺 、 三乙胺 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 27.33h， 生成 4-{(E)-5-[4-((S)-2-Hexanoylamino-2-methoxycarbonyl-ethyl)-phenyl]-pent-2-en-4-ynyl}-piperidine-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Non-Peptide Fibrinogen Receptor Antagonists. 2. Optimization of a Tyrosine Template as a Mimic for Arg-Gly-Asp

  摘要：

  Inhibitors of platelet-fibrinogen binding offer an opportunity to interrupt the final, common pathway for platelet aggregation. Small molecule inhibitors of the platelet fibrinogen receptor GPIIb/IIIa were prepared and evaluated for their ability to prevent platelet aggregation. Compound 23m (L-700,462/MK-383) inhibited in vitro platelet aggregation with an IC50 of 9 nM and demonstrated a selectivity of > 24 000-fold between platelet and human umbilical vein endothelial cell fibrinogen receptors. Dose-dependent inhibition of ex vivo platelet aggregation induced by ADP was achieved with iv infusions of 0.1-10 mu g/kg/min of 23m in anesthetized dogs, with 10 mu g/kg/min completely inhibiting platelet aggregation during the entire 6 h infusion protocol. Platelet aggregatability returned rapidly after the termination of the 23m infusions. These features suggest that 23m may be useful in the treatment of arterial occlusive disorders.

  DOI：

  10.1021/jm00042a007