1-(1,1-Dimethylethyl) 4-[4-[4-[(2S)-2-carboxy-2-[[(phenylmethoxy)carbonyl]amino]ethyl]phenoxy]butyl]-1-piperidinecarboxylate | 142355-84-8

• 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: 1-(1,1-Dimethylethyl) 4-[4-[4-[(2S)-2-carboxy-2-[[(phenylmethoxy)carbonyl]amino]ethyl]phenoxy]butyl]-1-piperidinecarboxylate
• 英文别名: (2S)-3-[4-[4-[1-[(2-methylpropan-2-yl)oxycarbonyl]piperidin-4-yl]butoxy]phenyl]-2-(phenylmethoxycarbonylamino)propanoic acid
• CAS: 142355-84-8
• 化学式: C₃₁H₄₂N₂O₇
• 分子量: 554.684
• InChiKey: PSKNOZCWXXYGHC-MHZLTWQESA-N

物化性质

• 沸点：
  703.9±60.0 °C(Predicted)
• 密度：
  1.170±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  40
• 可旋转键数：
  15
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  114
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1-(1,1-Dimethylethyl) 4-[4-[4-[(2S)-2-carboxy-2-[[(phenylmethoxy)carbonyl]amino]ethyl]phenoxy]butyl]-1-piperidinecarboxylate 在 palladium on activated charcoal 盐酸 、 sodium hydroxide 、 氢气 、 sodium carbonate 作用下， 以 乙醇 、 水 、 乙酸乙酯 为溶剂， 反应 15.5h， 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 、 二氯甲烷 、 乙酸乙酯 、 乙腈 为溶剂， 反应 45.83h， 生成 1-(1,1-Dimethylethyl) 4-[4-[4-[(2S)-2-carboxy-2-[[(phenylmethoxy)carbonyl]amino]ethyl]phenoxy]butyl]-1-piperidinecarboxylate
  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。
• Synthesis of RGD Analogs as Potential Vectors for Targeted Drug Delivery
  作者：Ji Jiang、Wei Wang、David C. Sane、Binghe Wang

  DOI：10.1006/bioo.2001.1227

  日期：2001.12

  RGD analogs bind to integrin receptors with high affinity and therefore have the potential to be used as vectors for the targeted delivery of pharmaceutical agents to designated sites. Critical to this application is the ability to synthesize RGD analogs with different side chain functional groups that allow for the ready tethering of pharmaceutical agents without sacrificing their affinity for the

  RGD类似物以高亲和力与整联蛋白受体结合，因此有潜力用作将药物靶向递送至指定部位的载体。对于该应用而言，至关重要的是具有不同侧链官能团的RGD类似物的合成能力，从而可以方便地束缚药物，而又不会显着牺牲其对靶受体的亲和力。制备了一系列打算用作药物递送载体的RGD类似物，并评估了它们通过结合糖蛋白IIb / IIIa抑制血小板聚集的能力。其中，化合物11对ADP活化的血小板的IC50最低。发现这种RGD类似物可以很好地耐受带有各种官能团如酰胺，胺，酯，受保护的胺和聚乙二醇的侧链修饰。具有聚（乙二醇）侧链修饰的化合物保留了对糖蛋白IIb / IIIa的高亲和力（IC50 150 nM）这一事实表明，在不显着牺牲其对RGD类似物的亲和力的情况下，可以将相当大的药剂与这些RGD类似物束缚。预期的受体。
• Novel sulfonamide fibrinogen receptor antagonists
  申请人：Merck & Co., Inc.

  公开号：US05292756A1

  公开（公告）日：1994-03-08

  A series of non-peptide derivatives of the formula ##STR1## that are antagonists of the fibrinogen IIb/IIIa receptor and thus are platelet anti-aggregation compounds useful in the prevention and treatment of diseases caused by thrombus formation.

  一系列非肽衍生物的化学式为 ##STR1##，它们是纤维蛋白原IIb/IIIa受体的拮抗剂，因此是有用的血小板抗聚集化合物，可用于预防和治疗由血栓形成引起的疾病。
• J. Med. Chem. 1994, 37, 2537-2551
  作者：

  DOI：——

  日期：——
• PIPERIDYL-4-SUBSTITUTED THYROSINE DERIVATIVES AS SCINTIGRAPHIC IMAGING AGENTS FOR THE DIAGNOSIS OF THROMBOSIS
  申请人：DIATECH, INC.

  公开号：EP0750610A1

  公开（公告）日：1997-01-02