Fluorescent pyrazine derivatives and methods of using the same in assessing renal function

Abstract

The present invention relates to pyrazine derivatives such as those represented by Formulas I and II. X1 to X4 formulas I and II may be characterized as electron withdrawing groups, white Y1 to Y4 of Formulas I and II may be characterized as electron donating groups. Pyrazine derivatives of the present invention may be utilized in assessing organ (e.g., kidney) function. In a particular example, an effective amount of a pyrazine derivative that is capable of being renally cleared may be administered into a patient's body. The pyrazine derivative may capable of one or both absorbing and emanating spectral energy of at least about 400 nm (e.g., visible and/or infrared light). At least some of the derivative that is in the body may be exposed to spectral energy and, in turn, spectral energy may emanate from the derivative. This emanating spectral energy may be detected and utilized to determine renal function of the patient.

1 - 44 . (canceled) 
     
     
         45 . A method for preparing 2,5-diaminopyrazine-3,6-dicarboxylic acid, the method comprising irradiating with microwaves a hydrolysis mixture comprising 2,4,6,8-tetrahydroxypyrimido(4,5-g)pteridine or a salt thereof. 
     
     
         46 . The method of  claim 45 , wherein the irradiating heats the hydrolysis mixture as the 2,4,6,8-tetrahydroxypyrimido(4,5-g)pteridine or a salt thereof is hydrolyzed. 
     
     
         47 . The method of  claim 45 , wherein the microwaves have a frequency in a range of from about 300 MHz to about 30 GHz. 
     
     
         48 . The method of  claim 45 , wherein the hydrolysis mixture is an aqueous hydrolysis mixture. 
     
     
         49 . The method of  claim 45 , wherein the irradiating heats the hydrolysis mixture to a temperature within a range of from about 120° C. to about 180° C. 
     
     
         50 . The method of  claim 45 , wherein the hydrolysis mixture is irradiated for a period of from about 30 minutes to about 90 minutes. 
     
     
         51 . The method of  claim 45 , wherein the hydrolysis mixture is irradiated in a sealed microwave reactor. 
     
     
         52 . The method of  claim 45 , wherein the irradiating heats the hydrolysis mixture to a temperature within a range of from about 120° C. to about 140° C. for a period of from about 45 minutes to about 75 minutes. 
     
     
         53 . The method of  claim 45 , wherein the hydrolysis mixture further comprises a base. 
     
     
         54 . The method of  claim 45 , wherein the hydrolysis mixture further comprises a base selected from the group consisting of alkali metal hydroxides, potassium hydroxide, and sodium hydroxide. 
     
     
         55 . 2,5-diaminopyrazine-3,6-dicarboxylic acid produced according to the method of  claim 45 . 
     
     
         56 . A method for preparing 2,5-diaminopyrazine-3,6-dicarboxylate, the method comprising
 preparing the 2,5-diaminopyrazine-3,6-dicarboxylic acid according to  claim 45 ; and   acidifying the irradiated mixture.   
     
     
         57 . The method of  claim 56 , wherein the acidifying comprises acidifying the irradiated mixture with a mineral acid selected from the group consisting of hydrochloric acid, sulfuric acid, and phosphoric acid. 
     
     
         58 . 2,5-diaminopyrazine-3,6-dicarboxylate produced according to the method of  claim 56 .