bis(2,5-dioxopyrrolidin-1-yl) 5-(tributylstannyl)isophthalate | 1411598-55-4

• 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: bis(2,5-dioxopyrrolidin-1-yl) 5-(tributylstannyl)isophthalate
• 英文别名: Bis(2,5-dioxopyrrolidin-1-yl) 5-tributylstannylbenzene-1,3-dicarboxylate
• CAS: 1411598-55-4
• 化学式: C₂₈H₃₈N₂O₈Sn
• 分子量: 649.328
• InChiKey: RWQVFFDHQVMAMK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.18
• 重原子数：
  39.0
• 可旋转键数：
  14.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  127.36
• 氢给体数：
  0.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  2-氨基乙基单酰胺-DOTA-TRIS(T-BU酯) 、 bis(2,5-dioxopyrrolidin-1-yl) 5-(tributylstannyl)isophthalate 在 三乙胺 作用下， 以 二甲基亚砜 为溶剂， 反应 2.0h， 以38%的产率得到tri-tert-butyl 2,2',2"-(10-(2-((2-(3-(((2,5-dioxopyrrolidin-1-yl)oxy)carbonyl)-5-(tributylstannyl)benzamido)ethyl)amino)-2-oxoethyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl)triacetate
  参考文献：
  名称：

  [EN] PSMA TARGETED RADIOHALOGENATED UREA-POLYAMINOCARBOXYLATES FOR CANCER RADIOTHERAPY
  [FR] POLYAMINOCARBOXYLATES D'URÉE RADIOHALOGÉNÉS CIBLANT PSMA POUR LA RADIOTHÉRAPIE ANTICANCÉREUSE

  摘要：

  本发明涉及小分子放射性卤代PSMA抑制剂及其金属配合物，以及它们在放射性成像和放射性治疗中用于治疗与PSMA相关的疾病，包括前列腺癌。本发明还揭示了将小分子放射性卤代PSMA抑制剂与竞争性PSMA配体相结合以减少放射性卤代PSMA抑制剂的非靶向积累的组合。

  公开号：

  WO2019157037A1
• 作为产物：
  描述：

  5-碘间苯二甲酸二甲酯 在 4-二甲氨基吡啶 、 双三苯基磷二氯化钯 、 lithium hydroxide monohydrate 、 水 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 为溶剂， 反应 4.5h， 生成 bis(2,5-dioxopyrrolidin-1-yl) 5-(tributylstannyl)isophthalate
  参考文献：
  名称：

  SIB-DOTA: A trifunctional prosthetic group potentially amenable for multi-modal labeling that enhances tumor uptake of internalizing monoclonal antibodies

  摘要：

  A major drawback of internalizing monoclonal antibodies (mAbs) radioiodinated with direct electrophilic approaches is that tumor retention of radioactivity is compromised by the rapid washout of iodo-tyrosine, the primary labeled catabolite for mAbs labeled via this strategy. In our continuing efforts to develop more versatile residualizing labels that could overcome this problem, we have designed SIB-DOTA, a prosthetic labeling template that combines the features of the prototypical, dehalogenation-resistant N-succinimidyl 3-iodobenzoate (SIB) with DOTA, a useful macrocyclic chelator for labeling with radiometals. Herein we describe the synthesis of the unlabeled standard of this prosthetic moiety, its protected tin precursor, and radioiodinated SIB-DOTA. An anti-EGFRvIII-reactive mAb, L8A4 was radiolabeled with [I-131]SIB-DOTA in 27.1 +/- 6.2% (n = 2) conjugation yields and its targeting properties to the same mAb labeled with [I-125]SGMIB both in vitro and in vivo using U87MG.Delta EGFR cells and xenografts were compared. In vitro paired-label internalization assays showed that the intracellular radioactivity from [I-131]SIB-DOTA-L8A4 was 21.4 +/- 0.5% and 26.2 +/- 1.1% of initially bound radioactivity at 16 and 24 h, respectively. In comparison, these values for [I-125]SGMIB-L8A4 were 16.7 +/- 0.5% and 14.9 +/- 1.1%. Similarly, the SIB-DOTA prosthetic group provided better tumor targeting in vivo than SGMIB over 8 d period. These results suggest that SIB-DOTA warrants further evaluation as a residualizing agent for labeling internalizing mAbs including those targeted to EGFRvIII. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.10.025