9-substituted minocycline compounds

Abstract

The present invention pertains, at least in part, to novel 9-substituted minocycline compounds. These minocycline compounds can be used to treat numerous tetracycline compound-responsive states, such as bacterial infections and neoplasms, as well as other known applications for minocycline and tetracycline compounds in general, such as blocking tetracycline efflux and modulation of gene expression.

1 - 4 . (canceled) 
     
     
         5 . A method for treating a tetracycline responsive state in a subject in need thereof, comprising administering to said subject a compound of formula II: 
       
         
           
           
               
               
           
         
       
       wherein:
 R 4′ , R 4″ , R 7′ , and R 7″  are each independently C 1 -C 6  alkyl; and 
 R 9  is methyl, ethyl, n-propyl, i-propyl, or C 1 -C 6  alkyl substituted with a substituent selected from the group consisting of hydroxyl, sulfonamide and cycloalkyl, or a pharmaceutically acceptable salt thereof, such that said tetracycline responsive state in said subject is treated. 
 
     
     
         6 . The method of  claim 5 , wherein R 4′ , R 4″ , R 7′ , and R 7″  are each methyl. 
     
     
         7 . The method of  claim 5 , wherein R 9  is ethyl. 
     
     
         8 . The method of  claim 5 , wherein R 9  is alkyl substituted with cycloalkyl. 
     
     
         9 . The method of  claim 11 , wherein said cycloalkyl is cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl. 
     
     
         10 . The method of  claim 12 , wherein said cycloalkyl is cyclopentyl. 
     
     
         11 . The method of  claim 5 , selected from the group consisting of: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         12 . A method for treating a tetracycline responsive state in a subject in need thereof, comprising administering to said subject an effective amount of a compound having the following structure: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, such that said tetracycline responsive state in said subject is treated. 
     
     
         13 . A method for treating a tetracycline responsive state in a subject, comprising administering to said subject a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of formula II: 
       
         
           
           
               
               
           
         
       
       wherein:
 R 4′ , R 4″ , R 7′ , and R 7′  are each independently C 1 -C 6  alkyl; and 
 R 9  is methyl, ethyl, n-propyl, i-propyl, or C 1 -C 6  alkyl substituted with a substituent selected from the group consisting of hydroxyl, sulfonamide and cycloalkyl, or a pharmaceutically acceptable salt thereof, such that said tetracycline responsive state in said subject is treated.