1-(phenylsulfonamido)-2-{4-[2-(piperidin-4-yl)ethoxy]benzamido}ethylphosphonic acid | 1354924-60-9

• 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: 1-(phenylsulfonamido)-2-{4-[2-(piperidin-4-yl)ethoxy]benzamido}ethylphosphonic acid
• 英文别名: [1-(benzenesulfonamido)-2-[[4-(2-piperidin-4-ylethoxy)benzoyl]amino]ethyl]phosphonic acid
• CAS: 1354924-60-9
• 化学式: C₂₂H₃₀N₃O₇PS
• 分子量: 511.536
• InChiKey: LZFBCZVLQBRVKH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.67
• 重原子数：
  34.0
• 可旋转键数：
  11.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  154.06
• 氢给体数：
  5.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  1-(phenylsulfonamido)-2-{4-[2-(piperidin-4-yl)ethoxy]benzamido}ethylphosphonic acid 在 ammonium acetate 、 溶剂黄146 作用下， 以 甲醇 、 水 、 乙腈 、 三氟乙酸 为溶剂， 生成 (S)-1-(phenylsulfonamido)-2-{4-[2-(piperidin-4-yl)ethoxy]benzamido}ethylphosphonic acid 、 (R)-1-(phenylsulfonamido)-2-{4-[2-(piperidin-4-yl)ethoxy]benzamido}ethylphosphonic 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 N,O-双三甲硅基乙酰胺 、 三异丙基硅烷 、 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-) 、 三氟乙酸 、 sodium hydroxide 、 1,1'-azodicarbonyl-dipiperidine 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 71.25h， 生成 1-(phenylsulfonamido)-2-{4-[2-(piperidin-4-yl)ethoxy]benzamido}ethylphosphonic 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

文献信息

• Tailoring of Integrin Ligands: Probing the Charge Capability of the Metal Ion-Dependent Adhesion Site
  作者：Markus Bollinger、Florian Manzenrieder、Roman Kolb、Alexander Bochen、Stefanie Neubauer、Luciana Marinelli、Vittorio Limongelli、Ettore Novellino、Georg Moessmer、Reinhard Pell、Wolfgang Lindner、Joseph Fanous、Amnon Hoffman、Horst Kessler

  DOI：10.1021/jm2013826

  日期：2012.1.26

  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.