Matrix Metalloproteinase Inhibitors and Imaging Agents, And Methods Using Same

Abstract

The present invention provides certain compounds, or salts or solvates thereof, which can be used as matrix metalloproteinase-targeted inhibitors or imaging agents.

What is claimed is: 
     
         1 . A compound of formula I, or a salt, solvate, stereoisomer, or tautomer thereof: 
       
         
           
           
               
               
           
         
       
       wherein:
 R is selected from the group consisting of OH, —NH 2 , —NHR′, —NR′R′, —NH(aryl), —NH(heteroaryl) and —NHR 1 ; 
 R 1  is selected from the group consisting of: 
 
       
         
           
           
               
               
           
         
         R 2  is selected from the group consisting of: 
       
       
         
           
           
               
               
           
         
         R 3  is selected from the group consisting of H, OH, OCH 3 , F,  18 F, 
       
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         each occurrence of n is independently an integer ranging from 0 to 30; 
         each occurrence of R′ is independently selected from the group consisting of C 1 -C 6  alkyl and C 3 -C 7  cycloalkyl; and 
         LG is a group capable of undergoing nucleophilic displacement. 
       
     
     
         2 . A pharmaceutical composition comprising at least one compound of  claim 1  and further comprising at least one pharmaceutically acceptable carrier. 
     
     
         3 . A method of evaluating a subject's risk of developing a cardiovascular disease or disorder, the method comprising:
 administering to a subject at least one compound of  claim 1 , wherein the at least one compound comprises a radioisotope or fluorophore,   acquiring an image of at least a portion of the subject's body, and   measuring the amount of compound bound to the imaged portion of the subject's body,   wherein, if the measured amount of bound compound is above a determined control amount, the subject is diagnosed as having an increased risk of developing the cardiovascular disease or disorder.   
     
     
         4 . The method of  claim 3 , wherein the subject is a mammal. 
     
     
         5 . The method of  claim 3 , wherein the subject is a human. 
     
     
         6 . A method of treating a matrix metalloproteinase-related disease or disorder in a subject, the method comprising administering to the subject in need thereof a therapeutically effective amount of at least one compound of  claim 1 . 
     
     
         7 . The method of  claim 6 , wherein the disease or disorder is at least one selected from the group consisting of cancers, inflammatory diseases, cardiovascular diseases, stroke, aneurysm, periodontitis, hepatitis, cirrhosis, portal hypertension, glomerulonephritis, atherosclerosis, emphysema, asthma, pulmonary fibrosis, autoimmune disorders of skin and dermal photoaging, rheumatoid arthritis, osteoarthritis, multiple sclerosis, Alzheimer's disease, chronic ulcerations, uterine involution and bone resorption. 
     
     
         8 . The method of  claim 6 , wherein the at least one compound is administered to the subject through a route selected from the group consisting of oral, nasal, inhalational, topical, buccal, rectal, pleural, peritoneal, intra-peritoneal, vaginal, intramuscular, subcutaneous, transdermal, epidural, intratracheal, otic, intraocular, intrathecal, and intravenous. 
     
     
         9 . The method of  claim 6 , wherein the subject is a mammal. 
     
     
         10 . The method of  claim 6 , wherein the subject is a human. 
     
     
         11 . A kit comprising at least one compound of  claim 1 , an applicator, and instructions to use the at least one compound to evaluate a subject's risk of developing a cardiovascular disease or disorder or treat a matrix metalloproteinase-related disease or disorder in a subject.