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    PROCESS FOR THE PREPARATION OF POLYETHER PHOSPHATES
    1.
    发明公开
    PROCESS FOR THE PREPARATION OF POLYETHER PHOSPHATES 失效
    制备聚醚磷酸酯的方法

    公开(公告)号：EP0998518A1

    公开(公告)日：2000-05-10

    申请号：EP98936508.5

    申请日：1998-07-24

    申请人： NYCOMED IMAGING AS

    发明人： SAINDANE, Manohar, Tukaram ,  LADD, David, Lee

    IPC分类号： C08G65/32 ,  C07F9/09

    CPC分类号： C08G65/3353 ,  C07F9/091 ,  C08G65/322

    摘要： The invention provides an improved process for the synthesis of compounds carrying at least one phosphate group, especially polyalkylene glycol phosphate compounds, said process comprising the steps of: (a) reacting a compound containing at least one primary alcohol moiety with a diaryl- or diaralkyl- halophosphate whereby to form the corresponding diaryl- or diaralkyl-phosphate ester; (b) reductively cleaving the resulting product; and (c) if desired, repeating steps (a) and (b) with the product of step (b) whereby to produce a compound carrying two or more phosphate groups. Advantages of the process in accordance with the invention are that this avoids the production of by-products and results in products which are low in impurities. Also provided are novel diaryl- and diaralkyl-phosphate ester compounds, in particular polyethylene glycol diphenylphosphate ester and derivatives thereof.

    摘要翻译： 本发明提供了用于合成携带至少一个磷酸酯基团的化合物，尤其是聚亚烷基二醇磷酸酯化合物的改进方法，所述方法包括以下步骤：（a）使含有至少一个伯醇部分的化合物与二芳基或二芳基 - 卤代磷酸酯，从而形成相应的二芳基或二芳基磷酸酯; （b）还原性裂解所得产物; 和（c）如果需要，用步骤（b）的产物重复步骤（a）和（b），由此产生携带两个或多个磷酸酯基团的化合物。 根据本发明的方法的优点在于，这避免了副产物的产生并导致杂质含量低的产物。 还提供了新的二芳基磷酸酯和二芳基磷酸酯化合物，特别是聚乙二醇二苯基磷酸酯及其衍生物。

    CYCLIC TRIAMINE CHELATING AGENTS
    3.
    发明公开
    CYCLIC TRIAMINE CHELATING AGENTS 失效
    CHELATBINDENDE CYCLISCHE TRIAMINE

    公开(公告)号：EP0755373A1

    公开(公告)日：1997-01-29

    申请号：EP95915920.0

    申请日：1995-04-12

    申请人： NYCOMED IMAGING AS

    发明人： ILLIG, Carl, Root ,  CAULFIELD, Thomas, Joseph ,  TONER, John, Luke ,  GUO, Peng ,  LADD, David, Lee

    IPC分类号： A61K49 ,  C07C227 ,  C07C229 ,  C07C237 ,  C07C265 ,  C07C327 ,  C07C331 ,  C07F5 ,  C07F9 ,  C07F11 ,  C07F13 ,  C07F15 ,  C09K3

    CPC分类号： A61K49/06 ,  C07C229/16 ,  C07C2601/14

    摘要： The present invention provides compounds of formula (I) wherein Z?1 and Z2¿ each represent the atoms necessary to complete a monocyclic or polycyclic carbocyclic or heterocyclic ring system, said Z?1 and Z2¿ independently optionally substituted with R?6 and R7¿, respectively; R?1, R2, R3 and R4¿ are independently carboxyalkyl (C¿1?-C2), -(CH2)n-C(=O)-NH-R?8¿, or -(CH¿2?)n-C(=O)-O-R?8, R5¿ is carboxyalkyl (C¿1?-C2); R?6 and R7¿ are independently, hydrogen, benzyl, or benzyloxy, said benzyl or benzyloxy optionally substituted with one, two or three substituents selected from the group consisting of amino, isocyanato (-N=C=O), isothiocyanato (-N=C=S), -NH-C(=O)-X or -NH-C(=S)-X; R8 is alkyl (C¿1?-C20), -(CH2)m-Ar, or polyhydroxyalkyl (C1-C20); n is 1 or 2; m is 1 to 15; X is a targeting moiety; and Ar is phenyl optionally substituted with one, two or three substituents selected from the group consisting of amino, acylamino, hydroxy, alkyl (C1-C5) and halogen. The compounds of the invention can be chelated with a metal ion and used as contrast agents for magnetic resonance imaging and for other applications. The present invention also provides pharmaceutical compositions comprising a compound of the invention and a pharmaceutically acceptable carrier or diluent. The invention further provides a method of providing an image of an internal region of a patient comprising administering to a patient a compound of the invention and scanning the patient using magnetic resonance imaging to obtain visible images of the region.

    摘要翻译： 本发明提供了与顺磁性金属离子螯合的式“IMAGE”化合物，其中Z 1和Z 2各自表示完成单环或多环碳环或杂环系统所必需的原子，所述Z 1和Z 2独立地任选被R 6和R 7取代， 分别; R1，R2，R3和R4分别是羧基烷基（C1-C2）， - （CH2）nC（= O）-NH-R8或 - （CH2）nC（= O）-O-R8 R5是羧基烷基 C2）; R6和R7独立地为氢，苄基或苄氧基，所述苄基或苄氧基任选被一个，两个或三个选自氨基，异氰酸酯基（-N = C = O），异硫氰酸酯（-N = C = S），-NH-C（= O）-X或-NH-C（= S）-X; R8是烷基（C1-C20）， - （CH2）m-Ar或多羟基烷基（C1-C20）; n为1或2; m为1〜15; X是靶向部分; 并且Ar是任选地被一个，两个或三个选自氨基，酰基氨基，羟基，烷基（C 1 -C 5）和卤素的取代基取代的苯基。