(2R,5R,8R,11R,14S,19R,22R,25R,28R)-14-amino-2,28-bis(19-(5-(6-(4,6-diphenylpyridin-2-yloxy)-2-methylhexan-2-yl)-1H-tetrazol-1-yl)-15-oxo-4,7,10-trioxa-14-azanonadecylcarbamoyl)-4,7,10,13,17,20,23,26-octaoxo-5,8,11,19,22,25-hexakis(sulfomethyl)-3,6,9,12,18,21,24,27-octaazanonacosane-1,29-disulfonic acid

• 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: (2R,5R,8R,11R,14S,19R,22R,25R,28R)-14-amino-2,28-bis(19-(5-(6-(4,6-diphenylpyridin-2-yloxy)-2-methylhexan-2-yl)-1H-tetrazol-1-yl)-15-oxo-4,7,10-trioxa-14-azanonadecylcarbamoyl)-4,7,10,13,17,20,23,26-octaoxo-5,8,11,19,22,25-hexakis(sulfomethyl)-3,6,9,12,18,21,24,27-octaazanonacosane-1,29-disulfonic acid
• 英文别名: (LTB4-(Csa)4)2-Glu-H Conjugate；(2R)-2-[[(4S)-4-amino-5-[[(2R)-1-[[(2R)-1-[[(2R)-1-[[(2R)-1-[3-[2-[2-[3-[5-[5-[6-(4,6-diphenylpyridin-2-yl)oxy-2-methylhexan-2-yl]tetrazol-1-yl]pentanoylamino]propoxy]ethoxy]ethoxy]propylamino]-1-oxo-3-sulfopropan-2-yl]amino]-1-oxo-3-sulfopropan-2-yl]amino]-1-oxo-3-sulfopropan-2-yl]amino]-1-oxo-3-sulfopropan-2-yl]amino]-5-oxopentanoyl]amino]-3-[[(2R)-1-[[(2R)-1-[[(2R)-1-[3-[2-[2-[3-[5-[5-[6-(4,6-diphenylpyridin-2-yl)oxy-2-methylhexan-2-yl]tetrazol-1-yl]pentanoylamino]propoxy]ethoxy]ethoxy]propylamino]-1-oxo-3-sulfopropan-2-yl]amino]-1-oxo-3-sulfopropan-2-yl]amino]-1-oxo-3-sulfopropan-2-yl]amino]-3-oxopropane-1-sulfonic acid
• 化学式: C₁₀₉H₁₅₉N₂₃O₄₄S₈
• 分子量: 2752.12
• InChiKey: LBTVXEXIIAMTIW-WSJKXOGOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -5.9
• 重原子数：
  184
• 可旋转键数：
  92
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  1060
• 氢给体数：
  21
• 氢受体数：
  53

反应信息

• 作为反应物：
  描述：

  (2R,5R,8R,11R,14S,19R,22R,25R,28R)-14-amino-2,28-bis(19-(5-(6-(4,6-diphenylpyridin-2-yloxy)-2-methylhexan-2-yl)-1H-tetrazol-1-yl)-15-oxo-4,7,10-trioxa-14-azanonadecylcarbamoyl)-4,7,10,13,17,20,23,26-octaoxo-5,8,11,19,22,25-hexakis(sulfomethyl)-3,6,9,12,18,21,24,27-octaazanonacosane-1,29-disulfonic acid 、 二亚乙基三胺五乙酸二酐 在 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.5h， 以96%的产率得到DPC11870-11
  参考文献：
  名称：

  Synthesis of Leukotriene B4 Antagonists Labeled with In-111 or Tc-99m to Image Infectious and Inflammatory Foci

  摘要：

  In previous studies we demonstrated that lipophilic Tc-99m-labeled LTB4 antagonist 1 (RP517) accumulated in infectious foci in rabbits, but hepatobiliary clearance hampered imaging of abdominal lesions. We now report the use of cysteic acid as a pharmacokinetic modifier to improve the water solubility and renal clearance of three hydrophilic analogues of 1. Divalent LTB4 antagonist 17 (DPC11870-11) is a DTPA conjugate for radiolabeling with In-111. Monovalent LTB4 antagonists 15 (BMS57868-88) and divalent LTB4 antagonist 18 (BMS5786881) are conjugated to bifunctional chelator HYNIC for radiolabeling with Tc-99m. The three compounds labeled efficiently with In-111 or Tc-99m with high radiochemical purity and specific activities. Scintigraphic images obtained in New Zealand White rabbits having acute intramuscular E. coli infection demonstrated that all agents were able to clearly visualize the abscess, and clearance was exclusively renal. The biodistribution of the Tc-99m-labeled LTB4 antagonists was affected by the coligands used with the HYNIC chelator and by the monovalent or divalent nature of the receptor binding moiety. The best scintigraphic images were obtained with monovalent HYNIC conjugate 15 using tricine and isonicotinic acid as coligands with HYNIC for coordination with Tc-99m.

  DOI：

  10.1021/jm050383h
• 作为产物：
  描述：

  在 苯甲醚 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 以134 mg的产率得到(2R,5R,8R,11R,14S,19R,22R,25R,28R)-14-amino-2,28-bis(19-(5-(6-(4,6-diphenylpyridin-2-yloxy)-2-methylhexan-2-yl)-1H-tetrazol-1-yl)-15-oxo-4,7,10-trioxa-14-azanonadecylcarbamoyl)-4,7,10,13,17,20,23,26-octaoxo-5,8,11,19,22,25-hexakis(sulfomethyl)-3,6,9,12,18,21,24,27-octaazanonacosane-1,29-disulfonic acid
  参考文献：
  名称：

  Synthesis of Leukotriene B4 Antagonists Labeled with In-111 or Tc-99m to Image Infectious and Inflammatory Foci

  摘要：

  In previous studies we demonstrated that lipophilic Tc-99m-labeled LTB4 antagonist 1 (RP517) accumulated in infectious foci in rabbits, but hepatobiliary clearance hampered imaging of abdominal lesions. We now report the use of cysteic acid as a pharmacokinetic modifier to improve the water solubility and renal clearance of three hydrophilic analogues of 1. Divalent LTB4 antagonist 17 (DPC11870-11) is a DTPA conjugate for radiolabeling with In-111. Monovalent LTB4 antagonists 15 (BMS57868-88) and divalent LTB4 antagonist 18 (BMS5786881) are conjugated to bifunctional chelator HYNIC for radiolabeling with Tc-99m. The three compounds labeled efficiently with In-111 or Tc-99m with high radiochemical purity and specific activities. Scintigraphic images obtained in New Zealand White rabbits having acute intramuscular E. coli infection demonstrated that all agents were able to clearly visualize the abscess, and clearance was exclusively renal. The biodistribution of the Tc-99m-labeled LTB4 antagonists was affected by the coligands used with the HYNIC chelator and by the monovalent or divalent nature of the receptor binding moiety. The best scintigraphic images were obtained with monovalent HYNIC conjugate 15 using tricine and isonicotinic acid as coligands with HYNIC for coordination with Tc-99m.

  DOI：

  10.1021/jm050383h

文献信息

• WO2008/79834
  申请人：——

  公开号：——

  公开（公告）日：——
• Preparation of Paramagnetic Nanoparticles Conjugated to Leukotriene B4 (LTB4) Receptor Antagonists, and Their Use as MRI Contrast Agents for the Detection of Infection and Inflammation
  申请人：Harris Thomas D.

  公开号：US20080213181A1

  公开（公告）日：2008-09-04

  Nanoparticle-based compositions and emulsions that are specifically targeted to leukotriene B4 (LTB4) receptors, and employing LTB4 receptor antagonist targeting agents, are set forth. In addition, there is provided the use of non-antibody based compositions for such targeting. The compositions of the invention are useful as imaging agents in diagnostic and therapeutic applications.
• Synthesis of Leukotriene B4 Antagonists Labeled with In-111 or Tc-99m to Image Infectious and Inflammatory Foci
  作者：Matthias Broekema、Julliëtte J. E. M. van Eerd、Wim J. G. Oyen、Frans H. M. Corstens、Rob M. J. Liskamp、Otto C. Boerman、Thomas D. Harris

  DOI：10.1021/jm050383h

  日期：2005.10.1

  In previous studies we demonstrated that lipophilic Tc-99m-labeled LTB4 antagonist 1 (RP517) accumulated in infectious foci in rabbits, but hepatobiliary clearance hampered imaging of abdominal lesions. We now report the use of cysteic acid as a pharmacokinetic modifier to improve the water solubility and renal clearance of three hydrophilic analogues of 1. Divalent LTB4 antagonist 17 (DPC11870-11) is a DTPA conjugate for radiolabeling with In-111. Monovalent LTB4 antagonists 15 (BMS57868-88) and divalent LTB4 antagonist 18 (BMS5786881) are conjugated to bifunctional chelator HYNIC for radiolabeling with Tc-99m. The three compounds labeled efficiently with In-111 or Tc-99m with high radiochemical purity and specific activities. Scintigraphic images obtained in New Zealand White rabbits having acute intramuscular E. coli infection demonstrated that all agents were able to clearly visualize the abscess, and clearance was exclusively renal. The biodistribution of the Tc-99m-labeled LTB4 antagonists was affected by the coligands used with the HYNIC chelator and by the monovalent or divalent nature of the receptor binding moiety. The best scintigraphic images were obtained with monovalent HYNIC conjugate 15 using tricine and isonicotinic acid as coligands with HYNIC for coordination with Tc-99m.