Tetracycline derivatives and methods of use thereof

Abstract

A treatment for inhibiting microbial or tumor growth is disclosed, which comprises adding to a subject in need of treatment an effective amount of one or more tetracycline derivatives.

1 - 3 . (canceled)  
   
   
       4 . A method for treating microbial growth or cancer which comprises administering to a subject in need of treatment for microbial growth or cancer an effective amount of a tetracycline compound or a salt thereof, the compound having a general formula:  
     
       
         
         
             
             
         
       
     
     wherein R is selected from CH 2 N(R a R b ) or  
     
       
         
         
             
             
         
       
       R a R b  are C 1 -C 6 ;  
       R c  and R d  are (CH 2 )n CHR e , n is 0 or 1, R e  is H, alkyl (C 1  to C 6 ), NH 2 , and X is NH, S, or CH 2 ;  
       R 1  and R 2  are H or N(R 9 ) 2  where R 9  is hydrogen or lower alkyl (C 1  to C 6 ), with the proviso that R 1  and R 2  can not both be N(R 9 ) 2 .  
       R 3  is H, OH, ═O, OCOR 10 , where R 10  is C 1  to C 6 , or alternatively, R 3  is N(R 9 ) 2  where R 9  is hydrogen or C 1  to C 6 , with the proviso that when R 23  is ═O or N(R 9 ) 2 , then R 4  and R 5  are H or CH 3  and R 4  and R 5  are not both CH 3  or H;  
         5   a  hydrogen is α or β;  
       R 4  and R 5  are H, CH 3  or F, with the proviso that when R 5  is CH 3 , then R 5  is H or F, and when R 5  is CH 3  then R 4  is H or F and R 4  and R 5  are not both F;  
       R 6  and R 8  are halogen, H, NO 2 , N 3 , N 2   +, C   2 H 5 OC(S)S—, CN, NR 10 R 11 , where R 10  and R 11  are H, alkyl (C 1  to C 10 ), and R 12 (CH 2 ) n CO—, where n is 0 to 5 and R 12  is H, NH 2 , mono or disubstituted amino selected from straight, branched or cyclized C 1  to C 10  groups, with the proviso that R 10  and R 11  are both R 12 (CH 2 ) n CO—, or, alternatively, R 8  is tertiary butyl;  
       R 7  is H or halogen, acetylene, R 12 -C 6 H 5 , where R 12  is NO 2 , halogen, acetylamino, amino, phenyl, alkyl, or alkoxy.  
     
   
   
       5 - 6 . (canceled)  
   
   
       7 . The method of  claim 4 , wherein the method is a method for treating microbial growth and the subject is in need of treatment for microbial growth.  
   
   
       8 . The method of  claim 4 , wherein the method is a method for treating cancer and the subject is in need of treatment for cancer.  
   
   
       9 . The method of  claim 8 , wherein the tetracycline compound is 4-epi-7-chlorotetracycline.  
   
   
       10 . The method of  claim 8 , wherein the tetracycline compound is 7-dimethylamino-6-demethyl-6-deoxy-tetracycline-9-diazonium.  
   
   
       11 . The method of  claim 8 , wherein the tetracycline compound is 9-azido-7-dimethylamino-6-demethyl-6-deoxy-tetracycline.  
   
   
       12 . The method of  claim 8 , wherein the tetracycline compound is 4-dedimethylamino-6-deoxy-5-hydroxytetracyline-9-diazonium.  
   
   
       13 . The method of  claim 8 , wherein the tetracycline compound is 9-tertbutyl-6-deoxy-5-hydroxytetracyline.