tert-butyl 4-[4-[4-[(2S)-3-methoxy-3-oxo-2-(phenylmethoxycarbonylamino)propyl]phenoxy]butyl]piperidine-1-carboxylate | 142373-56-6

• 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: tert-butyl 4-[4-[4-[(2S)-3-methoxy-3-oxo-2-(phenylmethoxycarbonylamino)propyl]phenoxy]butyl]piperidine-1-carboxylate
• CAS: 142373-56-6
• 化学式: C₃₂H₄₄N₂O₇
• 分子量: 568.711
• InChiKey: ABOJYWKFWLNJCD-NDEPHWFRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  41
• 可旋转键数：
  16
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  103
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-[4-[4-[(2S)-3-methoxy-3-oxo-2-(phenylmethoxycarbonylamino)propyl]phenoxy]butyl]piperidine-1-carboxylate 生成 1-Piperidinecarboxylic acid, 4-[4-[4-[(2S)-2-amino-3-methoxy-3-oxopropyl]phenoxy]butyl]-, 1,1-dimethylethyl ester
  参考文献：
  名称：

  Novel sulfonamide fibrinogen receptor antagonists

  摘要：

  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。

  公开号：

  US05292756A1
• 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 、 caesium carbonate 、 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 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 63.83h， 生成 tert-butyl 4-[4-[4-[(2S)-3-methoxy-3-oxo-2-(phenylmethoxycarbonylamino)propyl]phenoxy]butyl]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

文献信息

• 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。
• Synthesis and biological evaluation of PEG-tirofiban conjugates
  作者：Laurent Désaubry、Stéphanie Riché、Patricia Laeuffer、Jean-Pierre Cazenave

  DOI：10.1016/j.bmcl.2008.01.118

  日期：2008.3

  We have conjugated tiro. ban, an antagonist of the GPIIb/IIIa integrin receptor, to PEG, and shown that these polymers effectively inhibit platelet aggregation. This inhibition decreased with the size of the polymer. Our goal was to develop new cryoprotective agents to store frozen platelets. Surprisingly, tirofoban-conjugated PEG did not exhibit any protection. (c) 2008 Elsevier Ltd. All rights reserved.
• 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.
• J. Med. Chem. 1994, 37, 2537-2551
  作者：

  DOI：——

  日期：——