(2S)-2-amino-3-[4-[4-[1-[(2-methylpropan-2-yl)oxycarbonyl]piperidin-4-yl]butoxy]phenyl]propanoic acid | 142356-28-3

• 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: (2S)-2-amino-3-[4-[4-[1-[(2-methylpropan-2-yl)oxycarbonyl]piperidin-4-yl]butoxy]phenyl]propanoic acid
• CAS: 142356-28-3
• 化学式: C₂₃H₃₆N₂O₅
• 分子量: 420.549
• InChiKey: SJMMPKMCJGALRI-FQEVSTJZSA-N

物化性质

• 沸点：
  559.9±40.0 °C(Predicted)
• 密度：
  1.131±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  30
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  102
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (2S)-2-amino-3-[4-[4-[1-[(2-methylpropan-2-yl)oxycarbonyl]piperidin-4-yl]butoxy]phenyl]propanoic acid 在 盐酸 、 sodium hydroxide 、 sodium carbonate 作用下， 以 水 、 乙酸乙酯 为溶剂， 反应 3.5h， 生成 盐酸替罗非班
  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 palladium on activated charcoal sodium hydroxide 、 草酰氯 、 四溴化碳 、 硼烷 、 氢气 、 sodium hydride 、 二甲基亚砜 、 三乙胺 、 三苯基膦 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 、 乙酸乙酯 、 乙腈 为溶剂， 反应 57.83h， 生成 (2S)-2-amino-3-[4-[4-[1-[(2-methylpropan-2-yl)oxycarbonyl]piperidin-4-yl]butoxy]phenyl]propanoic acid
  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

文献信息

• Synthesis of Cyclic Prodrugs of Aggrastat and Its Analogue with a Modified Phenylpropionic Acid Linker
  作者：Xiaoping Song、Henry T. He、Teruna J. Siahaan

  DOI：10.1021/ol010282n

  日期：2002.2.1

  [structure: see text] The objective of this work was to synthesize cyclic prodrugs 1a and 1b from Aggrastat 2a and its analogue 2b, respectively, to improve their membrane permeation. Cyclic prodrugs 1a and 1b were formed using an ester bond between the -COOH group of Aggrastat or its analogue and the phenylpropionic acid linker 3 and an amide bond between the piperidinylamine and the -COOH group of

  [结构：见正文]这项工作的目的是分别从Aggrastat 2a及其类似物2b合成环状前药1a和1b，以改善其膜渗透性。如方案中所述，分别使用Aggrastat或其类似物的-COOH基团与苯基丙酸连接基3之间的酯键和哌啶子胺与连接基3的-COOH基团之间的酰胺键形成环状前药1a和1b。 4。
• US6248304B1
  申请人：——

  公开号：US6248304B1

  公开（公告）日：2001-06-19
• Non-Peptide Fibrinogen Receptor Antagonists. 2. Optimization of a Tyrosine Template as a Mimic for Arg-Gly-Asp
  作者：Melissa S. Egbertson、Charles T.-C. Chang、Mark E. Duggan、Robert J. Gould、Wasyl Halczenko、George D. Hartman、William L. Laswell、Joseph J. Lynch、Robert J. Lynch

  DOI：10.1021/jm00042a007

  日期：1994.8

  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.