1-(3-aza-8-carboxy-2-oxooctyl)-4,7,10-tris((1,1-dimethylethoxy)carbonylmethyl)-1,4,7,10-tetraazacyclododecane | 878750-09-5

• 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: 1-(3-aza-8-carboxy-2-oxooctyl)-4,7,10-tris((1,1-dimethylethoxy)carbonylmethyl)-1,4,7,10-tetraazacyclododecane
• 英文别名: 6-[2-(4,7,10-tris-tert-butoxycarbonylmethyl-1,4,7,10-tetraaza-cyclododec-1-yl)-acetylamino]-hexanoic acid；DOTA(tBu)₃-Ahx-OH；1-(3-aza-8-carboxy-2-oxa-octyl)-4,7,10-tris(tert-butyloxycarbonylmethyl)-1,4,7,10-tetraazacyclododecane；DOTA-tris(t-Bu)ester-C5-acid；6-[[2-[4,7,10-tris[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]-1,4,7,10-tetrazacyclododec-1-yl]acetyl]amino]hexanoic acid
• CAS: 878750-09-5
• 化学式: C₃₄H₆₃N₅O₉
• 分子量: 685.902
• InChiKey: VQIJUQAKYGQULG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  48
• 可旋转键数：
  20
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.85
• 拓扑面积：
  158
• 氢给体数：
  2
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  1-(3-aza-8-carboxy-2-oxooctyl)-4,7,10-tris((1,1-dimethylethoxy)carbonylmethyl)-1,4,7,10-tetraazacyclododecane 在 phosphate buffer 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 44.0h， 生成 1-((11-S)-3,10-diaza-13-carboxamido-11-carboxy-2,9-dioxotridecyl)-4,7,10-tris((1,1-dimethylethoxy)carbonylmethyl)-1,4,7,10-tetraazacyclododecane
  参考文献：
  名称：

  In Vitro and in Vivo Magnetic Resonance Detection of Tumor Cells by Targeting Glutamine Transporters with Gd-Based Probes

  摘要：

  The glutamine transporting system is up-regulated in tumor cells because cell proliferation requires the uptake of large quantities of glutamine. It has been found that the paramagnetic magnetic resonance imaging (MRI) reporter Gd-DOTAMA-C-6-Gln, where the glutamine residue is covalently bound to the Gd chelate through a C-6 spacer, accumulates in tumor cells both "in vitro" and "in vivo" experiments. The observation that the relaxivity of cellular pellets does not increase with the increase in the amounts of entrapped Gd chelate is taken as an indication that the internalization has occurred through receptor mediated endocytosis. The iv administration of Gd-DOTAMA-C-6-Gln allowed the MRI visualization of tumor masses in A/J mice grafted with the murine neuroblastoma cell line Neuro-2a and in Her2/neu transgenic mice developing multiple mammary carcinoma, respectively.

  DOI：

  10.1021/jm0601093
• 作为产物：
  描述：

  7-aza-9-bromo-8-oxononanoic acid benzyl ester 在 palladium on activated charcoal 氢气 、 potassium carbonate 作用下， 以 甲醇 、 乙腈 为溶剂， 反应 10.0h， 生成 1-(3-aza-8-carboxy-2-oxooctyl)-4,7,10-tris((1,1-dimethylethoxy)carbonylmethyl)-1,4,7,10-tetraazacyclododecane
  参考文献：
  名称：

  In Vitro and in Vivo Magnetic Resonance Detection of Tumor Cells by Targeting Glutamine Transporters with Gd-Based Probes

  摘要：

  The glutamine transporting system is up-regulated in tumor cells because cell proliferation requires the uptake of large quantities of glutamine. It has been found that the paramagnetic magnetic resonance imaging (MRI) reporter Gd-DOTAMA-C-6-Gln, where the glutamine residue is covalently bound to the Gd chelate through a C-6 spacer, accumulates in tumor cells both "in vitro" and "in vivo" experiments. The observation that the relaxivity of cellular pellets does not increase with the increase in the amounts of entrapped Gd chelate is taken as an indication that the internalization has occurred through receptor mediated endocytosis. The iv administration of Gd-DOTAMA-C-6-Gln allowed the MRI visualization of tumor masses in A/J mice grafted with the murine neuroblastoma cell line Neuro-2a and in Her2/neu transgenic mice developing multiple mammary carcinoma, respectively.

  DOI：

  10.1021/jm0601093

文献信息

• Dendrimersomes: a new vesicular nano-platform for MR-molecular imaging applications
  作者：Miriam Filippi、Jonathan Martinelli、Gilberto Mulas、Marisa Ferraretto、Eline Teirlinck、Mauro Botta、Lorenzo Tei、Enzo Terreno

  DOI：10.1039/c3cc49584a

  日期：——

  Vesicles formed by Janus dendrimers (dendrimersomes) loaded with hydrophilic or amphiphilic MRI probes show great potential as an efficient novel MRI nanosystem.

  Janus树状分子形成的囊泡（树状体）装载了亲水性或亲媒性MRI探针，显示出作为高效新型MRI纳米系统的巨大潜力。
• Biotinylation of a MRI/Gd BNCT theranostic agent to access a novel tumour-targeted delivery system
  作者：Alberto Lanfranco、Diego Alberti、Stefano Parisotto、Polyssena Renzi、Valentin Lecomte、Simonetta Geninatti Crich、Annamaria Deagostino

  DOI：10.1039/d2ob00764a

  日期：——

  functionalisation in two different steps with biotin as the biological vector and Gd-DOTA as the MRI probe and GdNCT agent. Cell uptake was evaluated on HeLa tumour cells overexpressing biotin receptors. The internalised boron is proportional to the concentration of the theranostic agent incubated in the presence of cells. A maximum value of 77 ppm is reached and a well detectable signal intensity increase

  为了以协同方式利用生物素的高肿瘤特异性和 BNCT 的选择性，本文报道了一种新的基于生物素的 BNCT（硼中子捕获疗法）-MRI 治疗诊断（Gd-AL01 ）。关键是制备中间体，其中邻碳硼烷与两个通过正交保护的氨基相连利用两个连续的光信反应。目的是在两个不同的步骤中将其功能化，生物素作为生物载体，Gd-DOTA 作为 MRI 探针和 GdNCT 试剂。在过度表达生物素受体的 HeLa 肿瘤细胞上评估细胞摄取。内化的硼与在细胞存在下孵育的治疗诊断剂的浓度成比例。达到 77 ppm 的最大值，并且在 HeLa 细胞的T 1加权图像中观察到可很好检测到的信号强度增加，这与临床使用的 GdHPDO3A 不同，后者未检测到对比度。这些优异的结果表明，Gd-AL01可用作 BNCT 研究中的治疗诊断探针。
• Conjugate comprising a neurotensin receptor ligand and use thereof
  申请人：3B Pharmaceuticals GmbH

  公开号：EP2954934A1

  公开（公告）日：2015-12-16

  The present invention is related to a conjugate comprising a structure of general formula (1)         [TM1] - [AD1] - [LM] - [AD2] - [TM2]     (1), wherein TM1 is a first targeting moiety, wherein the first targeting moiety is capable of binding to a first target, AD1 is a first adapter moiety or is absent, LM is a linker moiety or is absent, AD2 is a second adapter moiety or is absent, and TM2 is a second targeting moiety, wherein the second targeting moiety is capable of binding to a second target; wherein the first targeting moiety and/or the second targeting moiety is a compound of formula (2): wherein R1 is selected from the group consisting of hydrogen, methyl and cyclopropylmethyl; AA-COOH is an amino acid selected from the group consisting of 2-amino-2-adamantane carboxylic acid, cyclohexylglycine and 9-amino-bicyclo[3.3.1]nonane-9-carboxylic acid; R2 is selected from the group consisting of (C1-C6)alkyl, (C3-C8)cycloalkyl, (C3C8)cycloalkylmethyl, halogen, nitro and trifluoromethyl; ALK is (C2-C5)alkylidene; R3, R4 and R5 are each and independently selected from the group consisting of hydrogen and (C1-C4)alkyl under the proviso that one of R3, R4 and R5 is of the following formula (3) wherein ALK' is (C2-C5)alkylidene; R6 is selected from the group consisting of hydrogen and (C1-C4)alkyl; and R7 is a bond; or a pharmacologically acceptable salt, solvate or hydrate thereof.

  本发明涉及一种包含通式（1）结构的共轭物 [TM1] - [AD1] - [LM] - [AD2] - [TM2] (1)、 其中 TM1 是第一靶向分子，其中第一靶向分子能够与第一靶点结合、 AD1 是第一适配基团或不存在、 LM 是连接分子或不存在、 AD2 是第二适配基团或不存在，以及 TM2 是第二靶向分子，其中第二靶向分子能与第二靶点结合； 其中第一靶向分子和/或第二靶向分子为式（2）化合物： 其中 R1 选自由氢、甲基和环丙基甲基组成的组； AA-COOH 是一种氨基酸，选自由 2-氨基-2-金刚烷羧酸、环己基甘氨酸和 9-氨基-双环[3.3.1]壬烷-9-羧酸组成的组； R2 选自(C1-C6)烷基、(C3-C8)环烷基、(C3C8)环烷基甲基、卤素、硝基和三氟甲基组成的组； ALK 是（C2-C5）亚烷基； R3、R4 和 R5 各自独立地选自氢和(C1-C4)烷基组成的组，但 R3、R4 和 R5 中的一个必须符合下式 (3) 其中 ALK' 是 (C2-C5) 亚烷基； R6 选自氢和（C1-C4）烷基组成的组；以及 R7 是键； 或其药理学上可接受的盐、溶液或水合物。
• Neurotensin receptor ligands
  申请人：3B Pharmaceuticals GmbH

  公开号：US10961199B2

  公开（公告）日：2021-03-30

  The present invention is related to a compound of formula (I) wherein R1 is selected from the group consisting of hydrogen, methyl and cyclopropylmethyl; AA-COOH is an amino acid selected from the group consisting of 2-amino-2-adamantane carboxylic acid, cyclohexylglycine and 9-amino-bicyclo[3.3.1]nonane-9-carboxylic acid; R2 is selected from the group consisting of (C1-C6)alkyl, (C3-C8)cycloalkyl, (C3-C5)cycloalkylmethyl, halogen, nitro and trifluoromethyl; ALK is (C2-C5)alkylidene; R3, R4 and R5 are each and independently selected from the group consisting of hydrogen and (C1-C4)alkyl under the proviso that one of R3, R4 and R5 is of the formula (II) wherein ALK′ is (C2-C5)alkylidene; R6 is selected from the group consisting of hydrogen and (C1-C4)alkyl; and R7 is selected from the group consisting of H and an Effector moiety; or a pharmacologically acceptable salt, solvate or hydrate thereof.

  本发明涉及式(I)化合物 其中 R1 选自氢、甲基和环丙基甲基组成的组；AA-COOH 是选自 2-氨基-2-金刚烷羧酸、环己基甘氨酸和 9-氨基-双环[3.3.1]壬烷-9-羧酸组成的组的氨基酸；R2 选自(C1-C6)烷基、(C3-C8)环烷基、(C3-C5)环烷基组成的组。R2选自由(C1-C6)烷基、(C3-C8)环烷基、(C3-C5)环烷基甲基、卤素、硝基和三氟甲基组成的组；ALK为(C2-C5)亚烷基；R3、R4和R5各自独立地选自由氢和(C1-C4)烷基组成的组，但R3、R4和R5中的一个为式(II)，其中ALK′为(C2-C5)亚烷基；R6 选自由氢和（C1-C4）烷基组成的组；以及 R7 选自由 H 和效应分子组成的组；或其药理学上可接受的盐、溶液或水合物。
• [EN] PARAMAGNETIC METAL POLYAMINO COMPLEXES FOR MRI VISUALIZATION OF INTERNALIZED POLYNUCLEOTIDES<br/>[FR] COMPLEXES METALLIQUES PARAMAGNETIQUES POUR LA VISUALISATION EN IRM DE POLYNUCLEOTIDES INTERNALISES
  申请人：BRACCO IMAGING SPA

  公开号：WO2006027244A3

  公开（公告）日：2006-11-30