Substituted tetracycline compounds

Abstract

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

1 - 33 . (canceled) 
     
     
         34 . A tetracycline compound of Formula (III): 
       
         
           
           
               
               
           
         
       
       wherein
 R 9  is R′—O—N═CR″—, R′—OC(═O)—, R 9a R 9b NC(═O)—, methoxycarbonyl substituted alkynyl, pyrazinyl, alkylaminocarbonylalkyl, methoxymethyl, methoxymethyl substituted alkynyl, dimethylaminocarbonyl, cyclopropyl, methyl, amino substituted pyridinyl, alkoxyalkyl, alkylcarbonyl, arylcarbonyl, pyrimidinyl, alkoxycarbonyl substituted alkynyl, oxazolyl, pyrazolyl, carboxylate, halogen, piperidinylcarbonyl, alkyoxyalkyl substituted alkynyl, pyridinyl, thiazolyl, substituted or unsubstituted arylthiocarbonyl, cyano, deuterated alkylaminoalkyl, pyrrolidonylcarbonyl, carboxylatecarbonyl, alkylcarbonyl substituted phenyl, cyano substituted pyridinyl, aminocarbonyl substituted phenyl, dialkylaminomethyl, substituted or unsubstituted thiophenyl, substituted or unsubstituted furanyl, alkylcarbonylamino substituted pyridinyl, dialkylamino substituted phenyl, carboxylate substituted phenyl, azepanylcarbonyl, or piperazinylcarbonyl; 
 R 10  is hydrogen or alkenyl; 
 R′ is unsubstituted alkyl, amino substituted alkyl, methoxy substituted alkyl, halogen substituted alkyl; 
 R″ is alkyl; 
 R 9a  is hydrogen or alkyl; 
 R 9b  is alkyl, hydroxyl, alkoxy, hydroxyalkyl, alkoxyalkyl, alkylcarbonylaminoalkyl, alkoxycarbonylalkyl, hydroxyalkyl, aryl, cycloalkyl or aminoalkyl; and pharmaceutically acceptable salts, esters and prodrugs thereof, provided that when R 9  is halogen, then R 10  is alkenyl. 
 
     
     
         35 - 65 . (canceled) 
     
     
         66 . The compound of  claim 34 , wherein R 9  is methoxycarbonyl substituted alkynyl, pyrazinyl, methoxymethyl, cyclopropyl, methyl, methoxymethyl substituted alkynyl, amino substituted pyridinyl, alkylcarbonyl, arylcarbonyl, pyrimidinyl, oxazolyl, pyrazolyl, carboxylate, pyridinyl, thiazolyl, substituted or unsubstituted thiophenyl, piperidinylcarbonyl, dialkylaminomethyl, cyano, substituted or unsubstituted arylthiocarbonyl, deuterated alkylaminoalkyl, substituted furanyl, isoxolazolyl, cyano substituted pyridinyl, alkylcarbonylamino substituted pyridinyl, dialkylamino substituted phenyl, pyrrolidonylcarbonyl, azepanylcarbonyl, carboxylatecarbonyl, alkylcarbonyl substituted phenyl, aminocarbonyl substituted phenyl, carboxylate substituted phenyl or piperazinylcarbonyl. 
     
     
         67 - 78 . (canceled) 
     
     
         79 . The tetracycline compound of  claim 34 , wherein said compound is: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         80 - 258 . (canceled) 
     
     
         259 . A method for treating a tetracycline responsive state in a subject, comprising administering to said subject an effective amount of a tetracycline compound of  claim 34 , such that said subject is treated. 
     
     
         260 . The method of  claim 259 , wherein said tetracycline responsive state is malaria. 
     
     
         261 . The method of  claim 259 , wherein said tetracycline responsive state is a bacterial infection, a viral infection, or a parasitic infection. 
     
     
         262 - 265 . (canceled) 
     
     
         266 . The method of  claim 259 , wherein said tetracycline associated state is multiple sclerosis. 
     
     
         267 . The method of  claim 259 , wherein said subject is a human. 
     
     
         268 . The method of  claim 259 , wherein said tetracycline compound is administered with a pharmaceutically acceptable carrier. 
     
     
         269 . A pharmaceutical composition comprising a therapeutically effective amount of a tetracycline compound of  claim 34  and a pharmaceutically acceptable carrier. 
     
     
         270 . The tetracycline compound of  claim 79 , wherein said compound is: 
       
         
           
           
               
               
           
         
       
     
     
         271 . The method of  claim 259 , wherein the tetracycline compound is: 
       
         
           
           
               
               
           
         
       
     
     
         272 . The pharmaceutical composition of  claim 269 , wherein the tetracycline compound is: