Modified Pyrazine Derivatives and Uses Thereof

Abstract

In some embodiments, the invention provides modified pyrazine derivatives containing a central pyrazine ring with two secondary amine groups attached directly to the central pyrazine ring and two amino carbonyl groups attached directly to the central pyrazine ring. The secondary amine groups are terminated by alkyl groups containing from 1 to 6 carbons. The amino carbonyl groups can be terminated by a wide range of substituents including, but not limited to, alkyl and alkylene groups, polyether groups, including poly(ethylene glycol) groups, secondary and tertiary amine groups, polyhydroxylated alkyl groups, amino carbonyl groups, amino thioketone groups, and combinations thereof. In some embodiments, the invention provides modified pyrazine derivatives useful as optical agents in a wide variety of biomedical imaging procedures, including diagnostic and imaging procedures. In an embodiment, for example, modified pyrazine derivatives are provided which are useful in monitoring organ and system functioning, for example in monitoring renal system functioning.

1 .- 50 . (canceled) 
     
     
         51 . A method for use in an optical imaging, medical imaging, diagnostic, visualization, monitoring, surgical, biomedical or therapeutic procedure, wherein the method comprises:
 (i) administering a diagnostically effective amount of a compound of the formula (FX1):   
       
         
           
           
               
               
           
         
         
           wherein: 
           each of R 1  and R 2  is —(CH 2 ) a (CH 2 CH 2 O) b R 3 , —(CH 2 CH 2 O) b R 3 , —(CH 2 ) c (CH 2 CH 2 O) d (CH 2 ),NR 4 CONR 5 (CH 2 ) f (CH 2 CH 2 O) b R 6 , —(CH 2 ) c (CH 2 CH 2 O) d (CH 2 ) e NR 4 CSNR 5  (CH 2 ) f (CH 2 CH 2 O) b R 6 , —(CH 2 ) c (CH 2 CH 2 O) d (CH 2 ) e CONR 4 (CH 2 ) f (CH 2 CH 2 O) b R 6 , —(CH 2 ) c (CH 2 CH 2 O) d (CH 2 ) e NR 4 SO 2 (CH 2 ) f (CH 2 CH 2 O) b R 6 , —(CH 2 ) c (CH 2 CH 2 O) d (CH 2 ) e SO 2 NR 4 (CH 2 ) f (CH 2 CH 2 O) b R 6 , —(CH 2 ) c (CH 2 CH 2 O) d (CH 2 ) e NR 4 CO(CH 2 ) f (CH 2 CH 2 O) b R 6 , —(CH 2 ) c  (CH 2 CH 2 O) d  (CH 2 ) e NR 4 CO 2 (CH 2 ) f (CH 2 CH 2 O) b R 6 , —(CH 2 ) c (CH 2 CH 2 O) d (CH 2 ) e OC(O)NR 4 (CH 2 ) f (CH 2 CH 2 O) b R 6 , or —(CH 2 ) a Y 1 ; 
           each Y 1  is independently —OR 3 , —(CHOH) c R 7 , —NR 8 R 9 , —CONR 8 R 9 , —NHCO(CH 2 ) a (CH 2 CH 2 O) b R 6  or —NHCO(CHOH) c R 7 ; 
           each of R 3 , R 4 , R 5 , R 6  and R 7  is independently —H or C 1 -C 6  alkyl; 
           each of R 8  and R 9  is independently —H, C 1 -C 3  alkyl, —(CH 2 ) a (CHOH) c R 7  or —(CH 2 ) a (CH 2 CH 2 O) b R 6 ; 
           each of a, c, e and f is independently an integer from 0 to 10; 
           each b is independently an integer from 1 to 120; 
           each d is independently an integer from 0 to 120; and 
           each of m and n is independently an integer from 0 to 5 to a subject's bodily fluid, wherein the compound is differentially separated from a bodily fluid of the subject by an organ, tissue or system in the subject; 
         
         (ii) exposing the administered compound to non-ionizing radiation;
 wherein exposing the administered compound to non-ionizing radiation causes the compound to luminesce; and 
 
         (ii) detecting the administered compound;
 wherein detecting the administered compound comprises detecting the luminescence from the administered compound.