(2S)-2-[[4-[(2-amino-4-oxo-3H-pteridin-6-yl)methylamino]benzoyl]amino]-5-[[(1S)-1-carboxy-2-(4-hydroxyphenyl)ethyl]amino]-5-oxopentanoic acid | 59453-08-6

• 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: (2S)-2-[[4-[(2-amino-4-oxo-3H-pteridin-6-yl)methylamino]benzoyl]amino]-5-[[(1S)-1-carboxy-2-(4-hydroxyphenyl)ethyl]amino]-5-oxopentanoic acid
• CAS: 59453-08-6
• 化学式: C₂₈H₂₈N₈O₈
• 分子量: 604.579
• InChiKey: LJECDMWTVDXWHX-PMACEKPBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  44
• 可旋转键数：
  13
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  258
• 氢给体数：
  8
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  (2S)-2-[[4-[(2-amino-4-oxo-3H-pteridin-6-yl)methylamino]benzoyl]amino]-5-[[(1S)-1-carboxy-2-(4-hydroxyphenyl)ethyl]amino]-5-oxopentanoic acid 在 sodium iodide 作用下， 反应 0.33h， 生成
  参考文献：
  名称：

  Radioiodinated Folic Acid Conjugates: Evaluation of a Valuable Concept To Improve Tumor-to-Background Contrast

  摘要：

  Folic acid radioconjugates can be used for targeting folate receptor positive (FR+) tumors. However, the high renal uptake of radiofolates is a drawback of this strategy, particularly with respect to a therapeutic application due to the risk of damage to the kidneys by particle radiation. The goal of this study was to develop and evaluate radioiodinated folate conjugates as a novel class of folate-based radiopharmaceuticals potentially suitable for therapeutic application. Two different folic acid conjugates, tyrosine-folate (1) and tyrosine-click-folate (3), were synthesized and radioiodinated using the Iodogen method resulting in [I-125]-2 and [I-123/131]-4. Both radiofolates were highly stable in mouse and human plasma. Determination of FR binding affinities using H-3-folic acid and FR+ KB tumor cells revealed affinities in the nanomolar range for 2 and 4. The cell uptake of [I-125]-2 and [I-128/131]-4 proved to be FR specific as it was blocked by the coincubation of folic acid. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) in vitro assays were employed for the determination of tumor cell viability upon exposure to [I-131]-4. Compared to untreated control cells, significantly reduced cell viability was observed for FR+ cancer cells (KB, IGROV-1, SKOV-3), while FR- cells (PC-3) were not affected. Biodistribution studies performed in tumor bearing nude mice showed the specific accumulation of both radiofolates in KB tumor xenografts ([I-125]-2: 3.43 +/- 0.28% ID/g; [I-125]-4: 2.28 +/- 0.46% ID/g 4 h p.i.) and increasing tumor-to-kidney ratios over time. The further improvement of the tumor-to-background contrast was achieved by preinjection of the mice with pemetrexed allowing excellent imaging via single-photon emission computed tomography (SPECT/CT). These findings confirmed the hypothesis that the application of radioiodinated folate conjugates may be a valuable concept to improve tumor-to-background contrast. The inhibitory effect of [I-131]-4 on FR+ cancer cells in vitro indicates the potential of this class of radiofolates for therapeutic application.

  DOI：

  10.1021/mp200511t

文献信息

• US3989812A
  申请人：——

  公开号：US3989812A

  公开（公告）日：1976-11-02
• US4091087A
  申请人：——

  公开号：US4091087A

  公开（公告）日：1978-05-23