Methods for treating resistant diseases using triazole containing macrolides

Abstract

Triazole-containing macrolide and ketolide antibiotics, therapeutic compositions containing them and methods of use for treating diseases caused by one or more resistant organisms are described.

What is claimed is: 
     
         1 . A method for treating a disease in a host animal caused at least in part by  Chlamydia, Ureaplasma,  or a combination thereof; the method comprising administering to the host animal a therapeutically effective amount of a compound of the formula 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, wherein:
 R 10  is hydrogen or acyl; 
 X is H; and Y is OR 7 ; where R 7  is a monosaccharide; or X and Y are taken together with the attached carbon to form carbonyl; 
 V is C(O), C(═NR 11 ), CH(NR 12 , R 13 ), or N(R 14 )CH 2 , where N(R 14 ) is attached to the C-10 carbon; wherein R 11  is hydroxy or alkoxy, R 12  and R 13  are each independently selected from the group consisting of hydrogen, hydroxy, alkyl, aryjalkyl, alkylaryl, alkoxy, heteroalkyl, aryl, heteroaryl, dimethylaminoalkyl, acyl, sulfonyl, ureido, and carbamoyl; and R 14  is hydrogen, hydroxy, alkyl, aralkyl, alkylaryl, alkoxy, heteroalkyl, aryl, heteroaryl, dimethylaminoalkyl, acyl, sulfonyl, ureido, or carbamoyl; 
 W is H, F, Cl, Br, I, or OH; 
 A is CH 2 , C(O), C(O)O, C(O)NH, S(O) 2 , S(O) 2 NH, C(O)NHS(O) 2 ; 
 B is (CH 2 )n where n is an integer ranging from 0-10, or B is an unsaturated carbon chain of 2-10 carbons; and 
 C is alkyl, arylalkyl, heteroalkyl, aryl, heteroaryl, or heteroarylalkyl, each of which is optionally substituted. 
 
     
     
         2 .- 42 . (canceled) 
     
     
         43 . The method of  claim 1  wherein R 10  is hydrogen. 
     
     
         44 . The method of  claim 1  wherein X is H; and Y is OR 7 . 
     
     
         45 . The method of  claim 1  wherein R 7  is cladinosyl. 
     
     
         46 . The method of  claim 1  wherein X and Y are taken together with the attached carbon to form carbonyl. 
     
     
         47 . The method of  claim 1  wherein V is C(O). 
     
     
         48 . The method of  claim 1  wherein W is H or F. 
     
     
         49 . The method of  claim 1  wherein A is CH 2 . 
     
     
         50 . The method of  claim 1  wherein B is (CH 2 ) n . 
     
     
         51 . The method of  claim 1  wherein C is aryl, heteroaryl, arylalkyl, or heteroarylalkyl, each of which is optionally substituted. 
     
     
         52 . A method for treating a disease in a host animal caused at least in part by  Legionella, Haemophilus, Mycobacterium leprae,  or a combination thereof; the method comprising administering to the host animal a therapeutically effective amount of a compound of the formula. 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, wherein:
 R 10  is hydrogen or acyl; 
 X is H; and Y is OR 7 ; where R 7  is a monosaccharide; or X and Y are taken together with the attached carbon to form carbonyl; 
 V is C(O), C(═NR 11 ), CH(NR 12 , R 13 ), or N(R 14 )CH 2 , where N(R 14 ) is attached to the C-10 carbon; wherein R 11  is hydroxy or alkoxy, R 12  and R 13  are each independently selected from the group consisting of hydrogen, hydroxy, alkyl, aralkyl, alkylaryl, alkoxy, heteroalkyl, aryl, heteroaryl, dimethylaminoalkyl, acyl, sulfonyl, ureido, and carbamoyl; and R 14  is hydrogen, hydroxy, alkyl, aralkyl, alkylaryl, alkoxy, heteroalkyl, aryl, heteroaryl, dimethylaminoalkyl, acyl, sulfonyl, ureido, or carbamoyl; 
 W is H, F, Cl, Br, I, or OH; 
 A is CH 2 , C(O), C(O)O, C(O)NH, S(O) 2 , S(O) 2 NH, C(O)NHS(O) 2 ; 
 B is (CH 2 )n where n is an integer ranging from 0-10, or B is an unsaturated carbon chain of 2-10 carbons; and 
 C is alkyl, arylalkyl, heteroalkyl, aryl, heteroaryl, or heteroarylalkyl, each of which is optionally substituted.