Quinolone inhibitors of lipoprotein-associated phospholipase a2

Abstract

The present invention relates to new quinolone inhibitors of lipoprotein-associated phospholipase A2 activity, pharmaceutical compositions thereof, and methods of use thereof

What is claimed is: 
     
         1 . A deuterium-enriched composition comprising compounds of Formula I: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, wherein:
 R 1 -R 38  are hydrogen or deuterium; and the composition has a deuterium enrichment of at least 10%. 
 
     
     
         2 . The composition as recited in  claim 1  wherein the composition has a deuterium enrichment of at least 50%. 
     
     
         3 . The composition as recited in  claim 1  wherein the composition has a deuterium enrichment of at least 90%. 
     
     
         4 . The composition as recited in  claim 1  wherein the composition has a deuterium enrichment of at least 98%. 
     
     
         5 . The composition as recited in any one of  claims 1  to  4  further comprising a pharmaceutically acceptable excipient or carrier. 
     
     
         6 . A method of treatment of a lipoprotein-associated phospholipase A2-mediated disorder comprising the administration of a therapeutically effective amount of a composition as recited in  claim 5  to a patient. 
     
     
         7 . The method as recited in  claim 6  wherein said disorder is selected from the group consisting of coronary disorders, primary and secondary coronary disorders, acute coronary disorders, atherosclerosis, peripheral vascular atherosclerosis, cerebrovascular atherosclerosis, rheumatoid arthritis, diabetes, stroke, myocardial infarction, reperfusion injury, acute and chronic inflammation, psoriasis, and asthma.