tert-butyl (2-((2-(3,5-dimethyl-1H-pyrazol-1-yl)ethyl)amino)ethyl)carbamate | 782501-76-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: tert-butyl (2-((2-(3,5-dimethyl-1H-pyrazol-1-yl)ethyl)amino)ethyl)carbamate
• 英文别名: tert-butyl (2-{[2-(3,5-dimethyl-1H-pyrazol-1-yl)ethyl]amino}ethyl)carbamate；2-[(O)-tert-butylcarboxamidoethylaminoethyl]-3,5-dimethylpyrazole；tert-butyl N-[2-[2-(3,5-dimethylpyrazol-1-yl)ethylamino]ethyl]carbamate
• CAS: 782501-76-2
• 化学式: C₁₄H₂₆N₄O₂
• 分子量: 282.386
• InChiKey: VGDFARULNUOXGB-UHFFFAOYSA-N

物化性质

• 沸点：
  428.0±45.0 °C(Predicted)
• 密度：
  1.08±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.61
• 重原子数：
  20.0
• 可旋转键数：
  6.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  68.18
• 氢给体数：
  2.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  tert-butyl (2-((2-(3,5-dimethyl-1H-pyrazol-1-yl)ethyl)amino)ethyl)carbamate 在 potassium iodide sodium hydroxide 、 potassium carbonate 作用下， 以 四氢呋喃 、 水 、 乙腈 为溶剂， 反应 272.0h， 生成 4-((2-(tert-butoxycarbonylamino)ethyl)(2-(3,5-dimethyl-1H-pyrazol-1-yl)ethyl)amino)-butanoic acid
  参考文献：
  名称：

  [EN] BIFUNCTIONAL TRIDENTATE PYRAZOLYL CONTAINING LIGANDS FOR RE AND TC TRICARBONYL COMPLEXES
  [FR] TRIDENTATE PYRAZOLYLE BIFONCTIONNEL CONTENANT DES LIGANDS POUR LES COMPLEXES RE, TC ET MN TRICARBONYLE

  摘要：

  本发明涉及一种螯合剂的普遍公式：（I），其中m为0或1；X为NR4或S；Y为SR5，NHR5或P（R5）2；R1和R3相同或不同，选自H，烷基或芳基；R2为H，COOH，NHR6或（CH2）nCOOR6；R4为H，烷基，芳基，（CH2）nCOOR6或（CH2）nOR6；R5为H，烷基，芳基，（CH2）nCOOR6或（CH2）nOR6，R6为H，烷基或芳基；n为1、2、3、4、5、6、7、8、9或10；当R1=R3=CH3时，R2、R4和R5不全为H。本发明还涉及一种利用该螯合剂制备放射标记生物分子的方法和试剂盒。

  公开号：

  WO2004091669A1
• 作为产物：
  描述：

  2-(叔丁氧羰基氧亚氨基)-2-苯乙腈 、 N-[2-(3,5-dimethyl-1H-pyrazol-1-yl)ethyl]ethane-1,2-diamine 以 四氢呋喃 为溶剂， 反应 2.0h， 生成 tert-butyl (2-((2-(3,5-dimethyl-1H-pyrazol-1-yl)ethyl)amino)ethyl)carbamate
  参考文献：
  名称：

  [EN] BIFUNCTIONAL TRIDENTATE PYRAZOLYL CONTAINING LIGANDS FOR RE AND TC TRICARBONYL COMPLEXES
  [FR] TRIDENTATE PYRAZOLYLE BIFONCTIONNEL CONTENANT DES LIGANDS POUR LES COMPLEXES RE, TC ET MN TRICARBONYLE

  摘要：

  本发明涉及一种螯合剂的普遍公式：（I），其中m为0或1；X为NR4或S；Y为SR5，NHR5或P（R5）2；R1和R3相同或不同，选自H，烷基或芳基；R2为H，COOH，NHR6或（CH2）nCOOR6；R4为H，烷基，芳基，（CH2）nCOOR6或（CH2）nOR6；R5为H，烷基，芳基，（CH2）nCOOR6或（CH2）nOR6，R6为H，烷基或芳基；n为1、2、3、4、5、6、7、8、9或10；当R1=R3=CH3时，R2、R4和R5不全为H。本发明还涉及一种利用该螯合剂制备放射标记生物分子的方法和试剂盒。

  公开号：

  WO2004091669A1

文献信息

• Novel estradiol based metal complexes of Tc-99m
  作者：Carina Neto、Maria Cristina Oliveira、Lurdes Gano、Fernanda Marques、Thies Thiemann、Isabel Santos

  DOI：10.1016/j.jinorgbio.2012.03.001

  日期：2012.6

  Aiming to contribute to the design of technetium imaging agents for estrogen receptor (ER) positive breast tumors, we have synthesized and evaluated the novel organometallic estradiol complexes (fac-[M(CO)3(κ3-10)]+ and fac-[M(CO)3(κ3-12) M = Re/99mTc) using two different bifunctional tridentate ligands (4 and 8). The rhenium complexes (13 and 14) were fully characterized by IR, 1H NMR, 13C NMR, mass

  以帮助实现锝成像剂的设计对雌激素受体（ER）阳性乳腺癌肿瘤，我们已经合成并评价的新颖的有机金属配合物的雌二醇（FAC - [M（CO）3（κ 3 -10）] +和FAC - [M（CO）3（κ 3 -12） M =的Re / 99米使用两种不同的双官能三齿配体（TC）4和8）。IR配合物（13和14）通过IR，1 H NMR，13 C NMR，质谱和元素分析进行了全面表征。该99米获得具有高放射化学纯度的Tc络合物（15和16），并表现出高的体外放射化学稳定性。为了初步了解这些复合物与靶向ER阳性肿瘤的相关性，还进行了表达ER的细胞系MCF-7中的ER结合亲和力测定和细胞内在化研究，表明非ER介导的摄取。
• A^99mTc(CO)₃-labeled benzylguanidine with persistent heart uptake
  作者：Bruno L. Oliveira、Maurício Morais、Lurdes Gano、Isabel Santos、João D. G. Correia

  DOI：10.1002/jlcr.3188

  日期：2014.5.15

  We describe the synthesis and biological evaluation of the cationic 99mTc–tricarbonyl complex fac-[99mTc(CO)3(κ3-L1)]+ (Tc1) anchored by a pyrazole-diamine-methylbenzylguanidine-based ligand (L1), as potentially useful for myocardial imaging. The rhenium complex fac-[Re(CO)3(κ3-L1)]+ (Re1) was prepared and characterized as a ‘cold’ surrogate of the radioactive complex. Cell uptake studies in a neuroblastoma cell line suggest that Tc1 uptake mechanism is related to the norepinephrine transporter (NET). Tissue distribution studies in CD1 mice showed that Tc1 presents high initial heart uptake and a slow washout from the heart (7.8 ± 1.3% injected dose per gram (ID/g), 30-min post-injection (p.i.); 6.3 ± 1.3% ID/g, 60-min p.i.), with heart to blood ratios of 11.8 and 9.0 at 30- and 60-min p.i., respectively. The uptake mechanism of Tc1 appears to be similar to that of metaiodobenzylguanidine (MIBG), as it can be reduced by coinjection with nonradioactive MIBG. The biodistribution profile of Tc2, where the benzylguanidine pharmacophore is absent, corroborates the fact that Tc1 does not accumulate in the heart by a simple diffusion mechanism but rather by a NET-mediated mechanism. The results confirm those obtained in the cell assays. Despite the persistent heart uptake found for Tc1, the high hepatic and renal uptake remains to be improved.

  我们描述了由吡唑-二胺-甲基苄基胍基配体 (L1) 锚定的阳离子 99mTc-三羰基复合物 fac-[99mTc(CO)3(κ3-L1)]+ (Tc1) 的合成和生物学评估，该复合物具有潜在的用途用于心肌成像。制备了铼络合物 fac-[Re(CO)3(κ3-L1)]+ (Re1)，并将其表征为放射性络合物的“冷”替代物。神经母细胞瘤细胞系的细胞摄取研究表明，Tc1 摄取机制与去甲肾上腺素转运蛋白 (NET) 有关。 CD1 小鼠的组织分布研究表明，Tc1 具有较高的初始心脏摄取量和从心脏的缓慢清除能力（每克注射剂量 (ID/g) 为 7.8±±1.3%，注射后 30 分钟 (p.i.)；注射后 30 分钟 (p.i.)；6.3±±1.3%） ID/g，注射后 60 分钟），注射后 30 分钟和 60 分钟时心血比分别为 11.8 和 9.0。 Tc1 的摄取机制似乎与间碘苄基胍 (MIBG) 相似，因为它可以通过与非放射性 MIBG 共注射来减少。 Tc2 的生物分布特征（其中不存在苄基胍药效团）证实了 Tc1 不是通过简单的扩散机制而是通过 NET 介导的机制在心脏中积聚的事实。结果证实了细胞测定中获得的结果。尽管心脏对 Tc1 的摄取持续存在，但肝脏和肾脏的高摄取仍有待改善。
• Mono- and dicationic Re(I)/99mTc(I) tricarbonyl complexes for the targeting of energized mitochondria
  作者：Carolina Moura、Filipa Mendes、Lurdes Gano、Isabel Santos、António Paulo

  DOI：10.1016/j.jinorgbio.2013.02.008

  日期：2013.6

  The enhanced negative mitochondrial membrane potential of tumor cells can increase the cell accumulation of triphenylphosphonium (TPP) derivatives, which prompted us to investigate TPP-containing Re(I)/Tc-99m organometallic compounds as probes for in vivo targeting of energized mitochondria. Novel compounds (Re1-Re4/Tc1-Tc4) were obtained with bifunctional chelators of the pyrazole-diamine (N,N,N-donors) and pyrazole-aminocarboxylic (N,N,O-donors) type, functionalized with TPP pharmacophores that have been introduced at the central amine of the chelators using different spacers. In this way, dicationic (Re1-Re2, Tc1-Tc2) and monocationic (Re3-Re4, Tc3-Tc4) complexes with variable lipophilicity were synthesized. The Tc-99m complexes (Tc1-Tc4) are highly stable under physiological conditions and their chemical identification was done by HPLC comparison with the Re congeners (Re1-Re4), which were fully characterized by common analytical techniques (electrospray ionization mass spectrometry (ESI-MS), IR, multinuclear NMR). The in vitro biological evaluation of Tc1-Tc4 was performed in a panel of human tumor cell lines (PC-3, MCF-7 and H69), including cell lines overexpressing P-glycoprotein (MCF-7/MDR1 and H69/Lx4), and in isolated mitochondria. All the tested complexes showed a low to moderate cellular and mitochondrial uptake and did not undergo significant P-glycoprotein (Pgp)-mediated efflux processes. In particular, the dication Tc2 and the monocation Tc4 presented the highest cellular and mitochondrial uptake. Their cellular uptake was shown to depend on the mitochondrial (Delta psi(m)) and plasma membrane (Delta psi(p)) potentials. Altogether, the biological properties of these compounds suggest that they might be relevant for the design of radioactive metalloprobes for in vivo targeting of mitochondria. (C) 2013 Elsevier Inc. All rights reserved.