tris(4-ethoxymethylpyrazolyl)methane | 1027618-37-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: tris(4-ethoxymethylpyrazolyl)methane
• 英文别名: 1-[Bis[4-(ethoxymethyl)pyrazol-1-yl]methyl]-4-(ethoxymethyl)pyrazole
• CAS: 1027618-37-6
• 化学式: C₁₉H₂₈N₆O₃
• 分子量: 388.47
• InChiKey: RCWCWTSMAFCEPX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  28
• 可旋转键数：
  12
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  81.2
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  fac-triaquatricarbonyltechnetium-99m(1+) 、 tris(4-ethoxymethylpyrazolyl)methane 以 乙醇 为溶剂， 生成 fac-[^99mTc(CO)₃{HC[4-(EtOCH₂)pz]₃}]⁺
  参考文献：
  名称：

  Re(I) and 99mTc(I) tricarbonyl complexes with ether-containing pyrazolyl-based chelators: Chemistry, biodistribution and metabolism

  摘要：

  Tris(pyrazolyl) methane chelators, L1-L3, containing one or two ether groups at different positions of the azole rings, were synthesized and fully characterized. These chelators enabled the synthesis of fac[Tc-99m(CO)(3){HC[4-(ROCH2) pz](3)}] _ (R = Me (Tc1), Et (Tc2)) and fac-[Tc-99m(CO)(3){HC[3,5-(EtOCH2)(2)pz](3)}](+) (Tc3) which were identified by HPLC in comparison with the rhenium counterparts. The evaluation of Tc1 -Tc3 in CD-1 mice has shown that the number and/ or nature of the ether groups greatly influence the biodistribution profile, pharmacokinetics and metabolic stability of these complexes. Tc1 and Tc2, bearing a unique ether substituent at the 4-position of the pyrazolyl ring, undergo metabolic transformation in vivo while Tc3 is not metabolized. The metabolization of Tc1 and Tc2 enhanced their rate of excretion but, most probably, also justify their negligible heart uptake in contrast with the high heart uptake of congener non-metabolizable complexes (Tc-99m-DMEOP and Tc-99m-TMEOP), which have recently emerged as potential myocardial imaging agents. The attempts made to identify the metabolites of Tc1 and Tc2 have shown that the metabolization of these compounds must involve the ether functions with probable formation of carboxylic acid derivatives. A comparative study with the congener fac-[Tc-99m(CO)(3){[4-(MeOCH2)pz](CH2)(2)NH(CH2)(2)NH2}](+) (Tc6) led us to confirm the formation of such type of metabolites. In fact, Tc6 is also metabolized in mice with formation of fac-[Tc-99m(CO)(3){[4-(HOCH2)pz](CH2)(2)NH(CH2)(2)NH2}](+) (Tc7) and fac-[Tc-99m(CO)(3){[4-(HOOC) pz](CH2)(2)NH(CH2)(2)NH2}](+) (Tc8), which were chemically identified by HPLC in comparison with the Re congeners (Re7 and Re8). (C) 2013 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.jorganchem.2013.11.013
• 作为产物：
  描述：

  1-trityl-4-ethoxymethylpyrazole 在 盐酸 、 四丁基溴化铵 、 sodium carbonate 作用下， 以 乙醇 、 氯仿 、 水 、 丙酮 为溶剂， 反应 74.0h， 生成 tris(4-ethoxymethylpyrazolyl)methane
  参考文献：
  名称：

  Re(I) and 99mTc(I) tricarbonyl complexes with ether-containing pyrazolyl-based chelators: Chemistry, biodistribution and metabolism

  摘要：

  Tris(pyrazolyl) methane chelators, L1-L3, containing one or two ether groups at different positions of the azole rings, were synthesized and fully characterized. These chelators enabled the synthesis of fac[Tc-99m(CO)(3){HC[4-(ROCH2) pz](3)}] _ (R = Me (Tc1), Et (Tc2)) and fac-[Tc-99m(CO)(3){HC[3,5-(EtOCH2)(2)pz](3)}](+) (Tc3) which were identified by HPLC in comparison with the rhenium counterparts. The evaluation of Tc1 -Tc3 in CD-1 mice has shown that the number and/ or nature of the ether groups greatly influence the biodistribution profile, pharmacokinetics and metabolic stability of these complexes. Tc1 and Tc2, bearing a unique ether substituent at the 4-position of the pyrazolyl ring, undergo metabolic transformation in vivo while Tc3 is not metabolized. The metabolization of Tc1 and Tc2 enhanced their rate of excretion but, most probably, also justify their negligible heart uptake in contrast with the high heart uptake of congener non-metabolizable complexes (Tc-99m-DMEOP and Tc-99m-TMEOP), which have recently emerged as potential myocardial imaging agents. The attempts made to identify the metabolites of Tc1 and Tc2 have shown that the metabolization of these compounds must involve the ether functions with probable formation of carboxylic acid derivatives. A comparative study with the congener fac-[Tc-99m(CO)(3){[4-(MeOCH2)pz](CH2)(2)NH(CH2)(2)NH2}](+) (Tc6) led us to confirm the formation of such type of metabolites. In fact, Tc6 is also metabolized in mice with formation of fac-[Tc-99m(CO)(3){[4-(HOCH2)pz](CH2)(2)NH(CH2)(2)NH2}](+) (Tc7) and fac-[Tc-99m(CO)(3){[4-(HOOC) pz](CH2)(2)NH(CH2)(2)NH2}](+) (Tc8), which were chemically identified by HPLC in comparison with the Re congeners (Re7 and Re8). (C) 2013 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.jorganchem.2013.11.013

文献信息

• Technetium-99m (I) Tricarbonyl Complexes with Tridentate Chelators for Myocardium Imaging
  申请人：Santos Isabel Rego

  公开号：US20100074842A1

  公开（公告）日：2010-03-25

  Chelators of the formulae (I), (II) and (III) and tricarbonyl complexes of radioisotopes of Tc and Re bound to them, for use in myocardial imaging.

  公式（I）、（II）和（III）的螯合剂及与它们结合的Tc和Re同位素的三羰基配合物，用于心肌成像。
• Tricarbonyl Complexes with Tridentate Chelators for Myocardium Imaging
  申请人：Mallinckrodt LLC

  公开号：US20130129620A1

  公开（公告）日：2013-05-23

  Chelators of the formulae (I), (II) and (III) and tricarbonyl complexes of radioisotopes of Tc and Re bound to them, for use in myocardial imaging.

  公式（I），（II）和（III）的螯合剂及与它们结合的Tc和Re放射性同位素的三羰基配合物，用于心肌成像。
• TRICARBONYL COMPLEXES WITH TRIDENTATE CHELATORS FOR MYOCARDIUM IMAGING
  申请人：Mallinckrodt Inc.

  公开号：EP2099452A2

  公开（公告）日：2009-09-16
• US8372379B2
  申请人：——

  公开号：US8372379B2

  公开（公告）日：2013-02-12
• US8940273B2
  申请人：——

  公开号：US8940273B2

  公开（公告）日：2015-01-27