CYCLIC TRIAMINE CHELATING AGENTS

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.