2-{4-[2-(N-(benzyloxycarbonyl)piperidin-4-yl)ethoxy]benzamido}-1-(phenylsulfonamido)ethylphosphinic acid | 1354924-81-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-{4-[2-(N-(benzyloxycarbonyl)piperidin-4-yl)ethoxy]benzamido}-1-(phenylsulfonamido)ethylphosphinic acid
• CAS: 1354924-81-4
• 化学式: C₃₀H₃₆N₃O₈PS
• 分子量: 629.671
• InChiKey: YKQQAGXDSRWGBB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.01
• 重原子数：
  43.0
• 可旋转键数：
  13.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  151.34
• 氢给体数：
  3.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  2-{4-[2-(N-(benzyloxycarbonyl)piperidin-4-yl)ethoxy]benzamido}-1-(phenylsulfonamido)ethylphosphinic acid 在 N,O-双三甲硅基乙酰胺 、 三异丙基硅烷 、 水 、 sulfur 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 16.0h， 生成 1-(phenylsulfonamido)-2-{4-[2-(piperidin-4-yl)ethoxy]benzamido}ethylthiophosphonic acid
  参考文献：
  名称：

  Tailoring of Integrin Ligands: Probing the Charge Capability of the Metal Ion-Dependent Adhesion Site

  摘要：

  Intervention in integrin-mediated cell adhesion and integrin signaling pathways is an ongoing area of research in medicinal chemistry and drug development. One key element in integrin ligand interaction is the coordination of the bivalent cation at the metal ion-dependent adhesion site (MIDAS) by a carboxylic acid function, a consistent feature of all integrin ligands. With the exception of the recently discovered hydroxamic acids, all bioisosteric attempts to replace the carboxylic acid of integrin ligands failed. We report that phosphinates as well as monomethyl phosphonates represent excellent isosters, when introduced into integrin antagonists for the platelet integrin alpha IIb beta 3. The novel inhibitors exhibit in vitro and ex vivo activities in the low nanomolar range. Steric and charge requirements of the MIDAS region were unraveled, thus paving the way for an in silico prediction of ligand activity and in turn the rational design of the next generation of integrin antagonists.

  DOI：

  10.1021/jm2013826
• 作为产物：
  描述：

  4-哌啶乙醇 在 三丁基膦 、 水 、 sodium carbonate 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 sodium hydroxide 、 1,1'-azodicarbonyl-dipiperidine 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 54.25h， 生成 2-{4-[2-(N-(benzyloxycarbonyl)piperidin-4-yl)ethoxy]benzamido}-1-(phenylsulfonamido)ethylphosphinic acid
  参考文献：
  名称：

  Tailoring of Integrin Ligands: Probing the Charge Capability of the Metal Ion-Dependent Adhesion Site

  摘要：

  Intervention in integrin-mediated cell adhesion and integrin signaling pathways is an ongoing area of research in medicinal chemistry and drug development. One key element in integrin ligand interaction is the coordination of the bivalent cation at the metal ion-dependent adhesion site (MIDAS) by a carboxylic acid function, a consistent feature of all integrin ligands. With the exception of the recently discovered hydroxamic acids, all bioisosteric attempts to replace the carboxylic acid of integrin ligands failed. We report that phosphinates as well as monomethyl phosphonates represent excellent isosters, when introduced into integrin antagonists for the platelet integrin alpha IIb beta 3. The novel inhibitors exhibit in vitro and ex vivo activities in the low nanomolar range. Steric and charge requirements of the MIDAS region were unraveled, thus paving the way for an in silico prediction of ligand activity and in turn the rational design of the next generation of integrin antagonists.

  DOI：

  10.1021/jm2013826