公开(公告)号：EP0639083B1

公开(公告)日：2001-07-18

申请号：EP92915130.6

申请日：1992-05-07

申请人： NYCOMED IMAGING AS

发明人： TONER, John, L. ,  HILBORN, David, A. ,  MURRAY, Bruce, J. ,  HOUSSAIN, Timothy, Z. ,  SNOW, Robert, A. ,  SAHA, Ashis, K. ,  PHILION, Richard ,  SHEARMAN, Clyde, W. ,  SHAH, Chandra West Gate Village, 500

IPC分类号： A61K47/48 ,  A61K51/10

CPC分类号： C07D213/40 ,  A61K47/6887 ,  A61K49/0002 ,  A61K49/0019 ,  A61K49/0058 ,  A61K51/10 ,  A61K51/1093 ,  A61K2121/00 ,  C07D213/36 ,  C07D213/38 ,  C07D213/42 ,  C07D471/04 ,  C07D471/08

摘要： A targeting radioactive immunoreagent comprises a metal radionuclide ion, a complexing agent, and an immunoreactive group covalently bonded to said complexing agent, the complexing agent having the structure (AI), wherein R represents hydrogen, alkyl, alkoxy, alkylthio, alkylamino, alkylformamido, aryl, aryloxy, heterocyclyl or a protein reactive group; R1 represents hydrogen, alkyl, alkoxy, alkylthio, alkylamino, alkylformamido, aryl, aryloxy, heterocyclyl or a protein reactive group; R2 represents hydroxy, carboxy, hydroxyalkyl, thioalkyl, formyl, carbonyliminodiacetic acid, methyleneiminodiacetic acid, methylenethioethyleneiminodiacetic acid, carboxyalkylthioalkyl, hydrazinylidenediacetic acid, or a salt of such acids, or two R2 groups, taken together, represent the atoms necessary to complete a macrocyclic ring structure containing at least one heteroatom coordinating site and at least one, preferably two alkylene groups forming part of the ring structure; R3 represents hydrogen, alkyl, alkoxy, alkylthio, alkylamino, alkylformamido, aryl, aryloxy, heterocyclyl or a protein reactive group; R4 represents hydrogen or a protein reactive group; n is 0 to 4; o is 0 or 1; m is 0 or 1; provided that at least one of n and m is 0 and at least one of R, R?1, R3 and R4¿ is a protein reactive group. In another aspect, this invention provides novel terpyridines, quaterpyridines, quinqepyridines, sexipyridines and phenanthrolines having the structure (AI). Preferred terpyridines have the structure (AI) above wherein n=1, o=1, m=0, and R is a protein reactive group or a phenyl substituted with a protein reactive group. Optionally, the phenyl may also contain one or more substituents selected from alkyl and alkoxy. Preferred phenanthrolines have the structure (AI) above wherein n=0, o=1, m=1 and at least one R4 is a protein reactive group. The targeting radioactive immunoreagents are particularly useful in therapeutic and diagnostic imaging compositions and methods.