DPC11870-11

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: DPC11870-11
• 英文别名: DTPA Conjugate；2-[2-[bis(carboxymethyl)amino]ethyl-[2-[[2-[[(2S)-1,5-bis[[(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]-1,5-dioxopentan-2-yl]amino]-2-oxoethyl]-(carboxymethyl)amino]ethyl]amino]acetic acid
• 化学式: C₁₂₃H₁₈₀N₂₆O₅₃S₈
• 分子量: 3127.45
• InChiKey: DIGMLMRBDDSXMD-MSOXLDFBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -11.7
• 重原子数：
  210
• 可旋转键数：
  109
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  1230
• 氢给体数：
  25
• 氢受体数：
  64

反应信息

• 作为产物：
  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

文献信息

• 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.