2,2′-(7,10-bis(phosphonomethyl)-1,4,7,10-tetraazacyclododecane-1,4-diyl)diacetic acid | 164065-39-8

• 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: 2,2′-(7,10-bis(phosphonomethyl)-1,4,7,10-tetraazacyclododecane-1,4-diyl)diacetic acid
• 英文别名: N,N'-Bis(carboxymethyl)-N",N'"-bis(dihydroxyphosphorylmethyl)-1,4,7,10-tetraazacyclododecane；1,4,7,10-tetraazacyclododecane-1,4-diacetic acid-7,10-dimethylenediphosphonic acid；2-[4-(Carboxymethyl)-7,10-bis(phosphonomethyl)-1,4,7,10-tetrazacyclododec-1-yl]acetic acid
• CAS: 164065-39-8
• 化学式: C₁₄H₃₀N₄O₁₀P₂
• 分子量: 476.361
• InChiKey: CPRSUKTVKBJGCB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -13.2
• 重原子数：
  30
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  203
• 氢给体数：
  6
• 氢受体数：
  14

反应信息

• 作为产物：
  描述：

  di-tert-butyl 2,2′-(7,10-bis((diethoxyphosphoryl)methyl)-1,4,7,10-tetraazacyclododecane-1,4-diyl)diacetate 在 盐酸 、 水 作用下， 反应 48.0h， 以0.7 g的产率得到2,2′-(7,10-bis(phosphonomethyl)-1,4,7,10-tetraazacyclododecane-1,4-diyl)diacetic acid
  参考文献：
  名称：

  A comparative study of trans- and cis-isomers of a bone-seeking agent, DO2A2P

  摘要：

  The macrocyclic bone-seeking agent, DO2A2P, bears a cyclen core and two pairs of peripheral phosphonate and carboxylate groups. The geometric disposition of the peripheral functionalities gives arise to a pair of geometric isomers: cis-DO2A2P and trans-DO2A2P. In order to compare the biological behavior of the isomer pair, cis-DO2A2P was synthesized. Both isomers were successfully radiolabeled with Lu-177, which might potentiate their applications in both radiotherapy and imaging of bone diseases. Through a set of biological assays including the hydroxyapatite binding, in vitro stability, and in vivo distribution, we demonstrated that the geometric pair of DO2A2P had virtually identical biological properties. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.12.016

文献信息

• 1,4,7,10-tetraazacyclododecane-1,4-diacetic acid derivatives as chelating agents
  申请人：Dibra S.p.A.

  公开号：US06342597B1

  公开（公告）日：2002-01-29

  Compounds of formula (I) in which R is in which R is hydrogen, a straight or branched or cyclic C1-C6 alkyl group, unsubstituted or substituted by 1 to 10 oxygen atoms, or a C1-C20 alkyl group, optionally interrupted by a phenylene, in turn substituted by a straight or branched C1-C6 alkyl group, unsubstituted or substituted by 1 to 3 C1-C7 alkyl groups; the phenylene group being unsubstituted or substituted by alkoxy, carboxy, sulfamoyl, hydroxyalkyl, amino groups; as well as its complexes with a bi- or trivalent metal ion having an atomic number from 20 to 31, 39, 42, 43, 44, 49, or from 57 to 83, as well as its salts with anions of physiologically acceptable organic acids chelated complexes of these compounds are used as contrast agents for nuclear magnetic resonance imaging.

  公式（I）中的化合物，其中R是氢，直链或支链或环状的C1-C6烷基基团，未取代或取代1至10个氧原子，或C1-C20烷基基团，可由苯基间断，而后由直链或支链C1-C6烷基基团取代或未取代，或取代1至3个C1-C7烷基基团；苯基团未取代或取代为烷氧基，羧基，磺胺酰，羟基烷基，氨基团；以及其与具有20至31，39，42，43，44，49的原子序数的双价或三价金属离子的络合物，或具有57至83的原子序数的金属离子的络合物，以及其与生理上可接受的有机酸阴离子的盐，这些化合物的螯合络合物用作核磁共振成像的造影剂。
• MRI image enhancement using complexes of paramagnetic cations and amine
  申请人：Concat, Ltd.

  公开号：US05409689A1

  公开（公告）日：1995-04-25

  Ligands with three or more nitrogen atoms incorporated into a linear or cyclic backbone structure, with the nitrogen atoms substituted with a combination of phosphonate groups and nonphosphonate groups, of which at least two are phosphonate groups, are disclosed. These ligands are combined with paramagnetic metal cations and administered in the form of pharmacologically acceptable salts, are useful as MRI contrast enhancement agents, which tend to localize in bone tissue without being conjugated to bone-specific biomolecules. Triazacyclononanes and tetraazacyclododecanes, with dihydroxyphosphorylmethyl or dihydroxyphosphorylethyl groups linked to the backbone nitrogens are preferred.

  揭示了含有三个或更多氮原子并入线性或环状骨架结构中的配体，其中氮原子被磷酸酯基团和非磷酸酯基团的组合所取代，其中至少有两个是磷酸酯基团。这些配体与顺磁金属阳离子结合，并以药理学可接受的盐的形式给予，可用作磁共振成像对比增强剂，倾向于在不与骨特异性生物分子结合的情况下定位于骨组织。偏好具有二羟基磷酰甲基或二羟基磷酰乙基基团连接到骨架氮原子的三氮杂环庚烷和四氮杂环十二烷。
• POLYAMINO PARAMAGNETIC CHELATES WHICH CONTAIN BOTH PHOSPHONATE AND NON-PHOSPHONATE MOIETIES FOR MRI
  申请人：CONCAT LTD.

  公开号：EP0717639A1

  公开（公告）日：1996-06-26
• EP0717639A4
  申请人：——

  公开号：EP0717639A4

  公开（公告）日：1998-04-01
• Process for the preparation of derivatives of 1,4,7,10-tetraazacyclododecane-1,4-diacetic acid
  申请人：BRACCO S.p.A.

  公开号：EP1047677B1

  公开（公告）日：2005-07-20