α-(2-carboxyethyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid | 656242-49-8

• 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: α-(2-carboxyethyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid
• 英文别名: DOTAGA；(r)-2-(4,7,10-Tris(carboxymethyl)-1,4,7,10-tetraazacyclododecan-1-yl)pentanedioic acid；(2R)-2-[4,7,10-tris(carboxymethyl)-1,4,7,10-tetrazacyclododec-1-yl]pentanedioic acid
• CAS: 656242-49-8
• 化学式: C₁₉H₃₂N₄O₁₀
• 分子量: 476.484
• InChiKey: DZTVAULYUGBHSF-CQSZACIVSA-N

物化性质

• 沸点：
  782.6±60.0 °C(Predicted)
• 密度：
  1.368±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -10.7
• 重原子数：
  33
• 可旋转键数：
  11
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.74
• 拓扑面积：
  200
• 氢给体数：
  5
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  α-(2-carboxyethyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid 、 氯化钆 以 H₂O 为溶剂， 生成 GdDOTAGA
  参考文献：
  名称：

  Large Relaxivity Enhancement of Paramagnetic Lipid Nanoparticles by Restricting the Local Motions of the Gd^III Chelates

  摘要：

  A Gd-III-DOTA-like complex bearing two aliphatic chains on adjacent acetic arms was designed, synthesized, and compared with its analogous monofunctionalized complex. A 1/T-1 NMR relaxometric study of the two amphiphilic complexes incorporated into micelles and liposomes showed an unprecedented relaxivity enhancement for the complex with two lipophilic side arms. This remarkable result, which is attributed to a favorable water exchange rate and increased rigidity of the system resulting from limiting of the local motion of the gadolinium center, represents an important advance in the development of highly efficient nanosystems for MRI applications.

  DOI：

  10.1021/ja101518v
• 作为产物：
  描述：

  (R)-5-(叔丁氧基)-5-氧代-4-(4,7,10-三(2-(叔丁氧基)-2-氧代乙基)-1,4,7,10-四氮杂环十二烷-1-戊基)戊酸 在 三氟乙酸 作用下， 生成 α-(2-carboxyethyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid
  参考文献：
  名称：

  Optically pure and enriched isomers of chelating ligands and contrast agents

  摘要：

  有机螯合配体、有机螯合配体前体和金属螯合物被披露。还描述了合成它们的方法，包括制备光学富集或光学纯度组合物的方法。

  公开号：

  US20060155120A1

文献信息

• [EN] HSP90-TARGETING CONJUGATES AND FORMULATIONS THEREOF<br/>[FR] CONJUGUÉS CIBLANT LA HSP90 ET FORMULATIONS ASSOCIÉES
  申请人：TARVEDA THERAPEUTICS INC

  公开号：WO2019195384A1

  公开（公告）日：2019-10-10

  Conjugates of an active agent attached to a targeting moiety, such as at least one HSP90 binding moiety, via a linker, have been designed. Such conjugates can provide improved temporospatial delivery of the active agent, improved biodistribution and penetration in tumor, and/or decreased toxicity. Methods of making the conjugates and the formulations thereof are provided. Methods of administering the formulations to a subject in need thereof are provided, for example, to treat or prevent cancer.

  已设计出将活性剂与靶向基团（例如至少一个HSP90结合基团）通过连接剂结合的共轭物。这种共轭物可以提供改善活性剂的时间空间传递、改善在肿瘤中的生物分布和穿透性，以及/或减少毒性。提供了制备这些共轭物及其配方的方法。提供了将这些配方用于治疗或预防癌症等需要的受试者的方法。
• [EN] HSP90-BINDING CONJUGATES AND FORMULATIONS THEREOF<br/>[FR] CONJUGUÉS LIÉS À HSP90 ET FORMULATIONS DE CEUX-CI
  申请人：TARVEDA THERAPEUTICS INC

  公开号：WO2020205948A1

  公开（公告）日：2020-10-08

  Conjugates of an active agent attached to a targeting moiety, such as at least one HSP90 binding moiety, via a linker, have been designed. Such conjugates can provide improved temporospatial delivery of the active agent, improved biodistribution and penetration in tumor, and/or decreased toxicity. Methods of making the conjugates and the formulations thereof are provided. Methods of administering the formulations to a subject in need thereof are provided, for example, to treat or prevent cancer.

  将附着到靶向基团上的活性药剂的共轭物，例如至少一个HSP90结合基团，通过连接剂设计。这样的共轭物可以提供改善的活性药剂的时间空间传递，改善在肿瘤中的生物分布和渗透，以及/或减少毒性。提供了制备这些共轭物和其配方的方法。提供了将这些配方用于需要的受试者的方法，例如用于治疗或预防癌症。
• [EN] PROSTATE-SPECIFIC MEMBRANE ANTIGEN TARGETED HIGH-AFFINITY AGENTS FOR ENDORADIOTHERAPY OF PROSTATE CANCER<br/>[FR] AGENTS À AFFINITÉ ÉLEVÉE CIBLANT UN ANTIGÈNE MEMBRANAIRE SPÉCIFIQUE DE LA PROSTATE POUR ENDORADIOTHÉRAPIE DU CANCER DE LA PROSTATE
  申请人：UNIV JOHNS HOPKINS

  公开号：WO2018222778A1

  公开（公告）日：2018-12-06

  Prostate-specific membrane antigen targeted high-affinity agents for endoradiotherapy of prostate cancer are disclosed.

  揭示了针对前列腺癌的内放射治疗的前列腺特异性膜抗原靶向高亲和力药物。
• [EN] FGFR3-TARGETED RADIOIMMUNOCONJUGATES AND USES THEREOF<br/>[FR] RADIOIMMUNOCONJUGUÉS CIBLÉS PAR FGFR3 ET LEURS UTILISATIONS
  申请人：FUSION PHARMACEUTICALS INC

  公开号：WO2021195131A1

  公开（公告）日：2021-09-30

  Radioimmunoconjugates including a chelating moiety or a metal complex thereof, a linker, and an FGFR3 targeting moiety. Pharmaceutical compositions of such radioimmunoconjugates and methods of treatment for conditions, e.g., cancer, using such pharmaceutical compositions.

  放射免疫结合物包括螯合基或其金属配合物、连接剂和FGFR3靶向基。这样的放射免疫结合物的制药组合物以及使用这样的制药组合物治疗癌症等疾病的方法。
• Comparison of MRI Properties between Multimeric DOTAGA and DO3A Gadolinium-Dendron Conjugates
  作者：Maleotane Ndiaye、Volodymyr Malytskyi、Thomas Vangijzegem、Félix Sauvage、Mike Wels、Cyril Cadiou、Juliette Moreau、Céline Henoumont、Sébastien Boutry、Robert N. Muller、Dominique Harakat、Stefaan De Smedt、Sophie Laurent、Françoise Chuburu

  DOI：10.1021/acs.inorgchem.9b01747

  日期：2019.10.7

  The inherent lack of sensitivity of MRI needs the development of new Gd contrast agents in order to extend 20Hz,37%, the application of this technique to cellular imaging. For this purpose, two multimeric MR contrast agents obtained by peptidic coupling between an amido amine dendron and GdDOTAGA chelates (premetalation strategy, G1-4GdDOTAGA) or DO3A derivatives which then were postmetalated (G1-4GdDO-3A) have been prepared. By comparison to the monomers, an increase of longitudinal relaxivity has been observed for both structures. Especially for G1-4GdDO-3A, a marked increase is observed between 20 and 60 MHz. This structure differs from G1-4GdDOTAGA by an increased rigidity due to the aromatic linker between each chelate and the organic framework. This has the effect of limiting local rotational movements, which has a positive impact on relaxivity.