tri-tert-butyl 11-(4-(bromomethyl) benzyl)-1,4,8,11-tetraazacyclotetradecane-1,4,8-tricarboxylate | 220980-81-4

• 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: tri-tert-butyl 11-(4-(bromomethyl) benzyl)-1,4,8,11-tetraazacyclotetradecane-1,4,8-tricarboxylate
• 英文别名: 1-[4-(Bromomethyl)phenylmethyl]-4,8,11-tri-(t-butoxycarbonyl)-1,4,8,11 tetraazacyclotetradecane；tritert-butyl 11-[[4-(bromomethyl)phenyl]methyl]-1,4,8,11-tetrazacyclotetradecane-1,4,8-tricarboxylate
• CAS: 220980-81-4
• 化学式: C₃₃H₅₅BrN₄O₆
• 分子量: 683.727
• InChiKey: VYYNCQGLBBDFPM-UHFFFAOYSA-N

物化性质

• 沸点：
  681.5±55.0 °C(Predicted)
• 密度：
  1.174±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  44
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  91.9
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  tri-tert-butyl 11-(4-(bromomethyl) benzyl)-1,4,8,11-tetraazacyclotetradecane-1,4,8-tricarboxylate 在 potassium carbonate 、 苯硫酚 作用下， 以 乙腈 为溶剂， 生成
  参考文献：
  名称：

  一种靶向趋化因子受体CXCR4的小分子类 PET显像剂

  摘要：

  本发明为一种靶向趋化因子受体CXCR4的小分子类PET显像剂及其制备方法，本发明设计合成了带有伯胺功能基团的新型CXCR4小分子拮抗剂AMD3465‑NH2，AMD3465‑NH2进一步与SFB反应，并用64Cu进行放射化学标记，得到高放化纯度的PET显像剂(64Cu)‑AMD3465‑SFB，该显像剂稳定性与水溶性好，体内血液清除快，主要经肾脏和肝脏代谢，在趋化因子受体CXCR4阳性表达的4T1荷瘤Balb/c鼠中摄取明显，肿瘤病灶部位显像对比度高，肿瘤分辨能力强，而且肿瘤是特异性摄取。这些实验结果说明(64Cu)‑AMD3465‑SFB在进行肿瘤PET显像方面具有很好的临床应用开发前景。

  公开号：

  CN110590744B
• 作为产物：
  描述：

  二碳酸二叔丁酯 在 potassium carbonate 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 16.5h， 生成 tri-tert-butyl 11-(4-(bromomethyl) benzyl)-1,4,8,11-tetraazacyclotetradecane-1,4,8-tricarboxylate
  参考文献：
  名称：

  [99mTc]TcAMD3465 作为 CXCR4 受体成像 SPECT 示踪剂的合成和评价

  摘要：

  CXCR4 在许多基于免疫学的疾病和癌症中发挥着重要作用。开发靶向 CXCR4 的放射性示踪剂可以为诊断和监测涉及受体失调的疾病提供有价值的工具。已报道并表征了将多种放射性核素掺入小分子、肽和 CXCR4 配体中。在本研究中，制备了具有高产率和放射化学纯度的 99m Tc 标记的 AMD3465。[ 99m Tc]TcAMD3465 的体外和体内研究显示出高稳定性和结合亲和力，亲水性 log P 值为 - 2.67。使用井型 Na(I) 检测器使用组织和器官样本研究生物分布研究，在肝脏、脾脏和骨骼中观察到高放射性积累，与这些器官中的高 CXCR4 表达一致。

  DOI：

  10.1007/s10967-020-07532-8

文献信息

• CXCR4 INHIBITING CARRIERS FOR NUCLEIC ACID DELIVERY
  申请人：Wayne State University

  公开号：US20140243397A1

  公开（公告）日：2014-08-28

  The present invention generally relates to carriers including polymers and lipids that comprise a CXCR4 inhibiting moiety. More specifically, these carriers are biodegradable and can be bioreducible polymers that comprise a CXCR4 inhibiting moiety. These carriers can be suitable for delivery of nucleic acids to cells. These carriers and pharmaceutical compositions can be used to treat various conditions including cancers and inflammation conditions.

  本发明通常涉及包括聚合物和脂质的载体，其包括CXCR4抑制物。更具体地说，这些载体是可生物降解的，可以是包含CXCR4抑制物的可生物还原聚合物。这些载体可以适用于将核酸传递到细胞。这些载体和制药组合物可用于治疗各种疾病，包括癌症和炎症疾病。
• Method for inducing chemotaxis in endothelial cells by administering stromal cell derived factor-1alpha
  申请人：SmithKline Beecham Corporation

  公开号：US20020107195A1

  公开（公告）日：2002-08-08

  CXCR4 and SDF-1&agr; polypeptides and polynucleotides and methods for producing such polypeptides by recombinant techniques are disclosed. Also disclosed are methods for utilizing CXCR4 and SDF-1&agr; polypeptides and polynucleotides in the design of protocols for the treatment of inflammatory diseases, angiogenic diseases, and infections, such Human Immunodeficiency Virus (HIV).

  本发明公开了CXCR4和SDF-1α多肽和多核苷酸以及通过重组技术生产这些多肽的方法。还公开了利用CXCR4和SDF-1α多肽和多核苷酸设计治疗炎症性疾病、血管生成性疾病和感染（如人类免疫缺陷病毒（HIV））方案的方法。
• 18F-Radiolabeling and Evaluation of an AMD3465 Derivative for PET Imaging of CXCR4 in a Mouse Breast Tumor Model
  作者：Huiqiang Li、Xiaochen Li、Lingyi Sun、Yanjie He、Li Wang、Yongju Gao、Dexing Zeng、Xinchang Pang、Junling Xu

  DOI：10.1021/acs.bioconjchem.4c00167

  日期：2024.5.15

  The exploration of pharmaceutically active agents and positron emission tomography (PET) tracers targeting CXCR4 has been a focal point in cancer research given its pivotal role in the development and progression of various cancers. While significant strides have been made in PET imaging with radiometal-labeled tracers, the landscape of 18F-labeled small molecule tracers remains relatively limited

  鉴于 CXCR4 在各种癌症的发生和发展中起着关键作用，针对 CXCR4 的药物活性剂和正电子发射断层扫描 （PET） 示踪剂的探索一直是癌症研究的重点。虽然使用放射性金属标记示踪剂进行 PET 成像取得了重大进展，但 18种 F 标记的小分子示踪剂的情况仍然相对有限。在此，我们介绍了一种新颖且有前途的衍生物 [18F]SFB-AMD3465，作为 CXCR4 的靶向 PET 示踪剂。该化合物是通过修饰 AMD3465 的吡啶环合成的，随后使用 [18F] SFB 用 18F 标记。该研究为 [18F]SFB-AMD3465 的设计、合成和生物学评估提供了全面的见解。体外和体内评估表明，在 CXCR4 过表达的 4T1 细胞系和相应的携带异种移植物的小鼠模型中，[18F]SFB-AMD3465 的 CXCR4 依赖性、特异性和敏感性摄取。这些发现有助于弥合 18种 F 标记的 PET 示踪剂中用于
• WO2008/21788
  申请人：——

  公开号：——

  公开（公告）日：——
• Redox-Driven Intramolecular Anion Translocation between Transition Metal Centres
  作者：Luigi Fabbrizzi、Francesco Gatti、Piersandro Pallavicini、Eugenia Zambarbieri

  DOI：10.1002/(sici)1521-3765(19990201)5:2<682::aid-chem682>3.0.co;2-e

  日期：1999.2.1

  In a two-component system containing two transition metal centres, M-1 and M-2, an anion X- coordinated to M-1 can be translocated to M-2, if i) the latter metal is redox active (through the M-2(n+)/M-2((n+1)+) change) and ii) the affinity towards X- decreases along the series: M-2((n+1)+)>M-1>M-2(n+). In these circumstances, when the M-1 similar to M-2 system is in its reduced form, X- stays on M-1; on oxidation X- moves to M-1. The above-mentioned model has been verified with the covalently linked two-component system i, in which a tripodal tetramine subunit (tren) hosts a Cu-II ion, and a tetramine macrocyclic subunit (cyclam) encircles a nickel centre, which is redox active through the Ni-II/Ni-III couple. Binding tendencies of inorganic anions towards the Cu-II, Ni-II and Ni-III ions, in an MeCN solution, were investigated and compared with those involving the separate components [Cu-II(2)](2+) and [Ni-II,Ni-III(3)](2+/3+). In general, affinity towards X- decreases along the series: Ni-III>Cu-II>Ni-II. Thus, we observed through spectroelectrochemical techniques that in the reduced form of the two-component system Cu(II)similar to Ni-II, the X- anion (Cl-, NCO-) is located on the Cu-II centre, whereas on Ni-II-to-Ni-III oxidation it is translocated to the Ni-III centre. The translocation is quickly reversible and, in the case of the oxidation resistant chloride anion, can be carried out indefinitely through consecutive oxidation and reduction processes, in a controlled potential electrolysis experiment. The intramolecular nature of the redox-driven anion translocation in the Cu(II)similar to Ni-II,Ni-III system is discussed and substantiated by considering the pertinent thermodynamic functions Delta H degrees and Delta S degrees, obtained by temperature dependent voltammetric studies. We conclude that the intramolecular Cl- translocation from Cu-II to Ni-III prevails over any other intermolecular process, due a more favourable entropy contribution.