Ester nitrates derivatives of aromatic aldehydes with multiple pharmalogic properties to treat sickle cell disease

Abstract

The invention provides new aromatic aldehyde compounds that have greater potency in increasing the affinity of Hb for oxygen, greater potency for preventing sickling, and additional pharmacologic properties that ameliorate other symptoms of SCD. The invention further provides methods for treating SCD by providing a subject having SCD with a compound according to the invention.

1 - 57 . (canceled) 
     
     
         58 . A method for treating a subject having sickle cell disease (SCD), comprising administering to the subject a therapeutically effective amount of a compound of the formula: 
       
         
           
           
               
               
           
         
         wherein R 1  is H, OH, alkyl, alkoxy, halogen, aryl, or O-aryl; 
         wherein R 2  is H or NO 2 ; 
         wherein X, Y, and Z are the same or different and are C or N; and 
         wherein n is 1-5, and 
         pharmaceutically acceptable salts thereof. 
       
     
     
         59 . A method of  claim 58  wherein the compound has the general formula 
       
         
           
           
               
               
           
         
         wherein R 1  is H, OH, alkyl, alkoxy, halogen, aryl, or O-aryl; and X, Y, and Z are the same or different and are C or N; and pharmaceutically acceptable salts thereof. 
       
     
     
         60 . The method of  claim 59  wherein the compound as the formula 
       
         
           
           
               
               
           
         
         and pharmaceutically acceptable salts thereof. 
       
     
     
         61 . The method of  claim 59  wherein the compound has the formula 
       
         
           
           
               
               
           
         
         and pharmaceutically acceptable salts thereof. 
       
     
     
         62 . The method of  claim 58  wherein the compound has the general formula 
       
         
           
           
               
               
           
         
         wherein R 1  is H, OH, alkyl, alkoxy, halogen, aryl, or O-aryl; and X, Y, and Z are the same or different and are C or N; and pharmaceutically acceptable salts thereof.