6-11 Bridged Oxime Erythromycin Derivatives

Abstract

The present invention discloses compounds of formula I, or pharmaceutically acceptable salts, esters, or prodrugs thereof: which exhibit antibacterial properties. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject in need of antibiotic treatment. The invention also relates to methods of treating a bacterial infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention. The invention further includes processes by which to make the compounds of the present invention.

1 - 13 . (canceled) 
   
   
       14 . A compound represented by Formula VI: 
     
       
         
         
             
             
         
       
     
     or a racemate, enantiomer, regioisomer, salt, ester, or prodrug thereof wherein
 X and Y are independently selected from the group consisting of: hydrogen, deuterium, halogen, R 1 , OR 1 , S(O) n R 1 , —NR 1 C(O)R 2 , —NR 1 C(O)NR 3 R 4 , —NR 1 S(O) n R 2 , —C(O)NR 3 R 4 , and —NR 3 R 4 ; 
 each of R 1  and R 2  is independently selected from the group consisting of: hydrogen, acyl, silane, a substituted or unsubstituted, saturated or unsaturated aliphatic group, a substituted or unsubstituted, saturated or unsaturated alicyclic group, a substituted or unsubstituted aromatic group, a substituted or unsubstituted heteroaromatic group, or a substituted or unsubstituted heterocyclic group; 
 each of R 3  and R 4  is independently selected from the group consisting of: hydrogen, acyl, a substituted or unsubstituted, saturated or unsaturated aliphatic group, a substituted or unsubstituted, saturated or unsaturated alicyclic group, a substituted or unsubstituted aromatic group, a substituted or unsubstituted heteroaromatic group, a substituted, or unsubstituted heterocyclic group; or can be taken together with the nitrogen atom to which they are attached to form a substituted or unsubstituted heterocyclic or heteroaromatic ring; 
 or X and Y, taken together with the carbon atom to which they are attached, are selected from the group consisting of: CO, C═CHR 1 , C═NR 1 , C═NC(O)R 1 , C═NOR 1 , C═NO(CH 2 ) m R 1 , C═NNHR 1 , C═NNHCOR 1 , C═NNHCONR 1 R 2 , C═NNHS(O) n R 1 , C═N—N═CHR 1 , C═N—NO 2 , or C═N—ONO; 
 L is selected from the group consisting of: hydrogen, a substituted or unsubstituted, saturated or unsaturated aliphatic group, a substituted or unsubstituted, saturated or unsaturated alicyclic group, a substituted or unsubstituted aromatic group, a substituted or unsubstituted heteroaromatic group, or a substituted or unsubstituted heterocyclic group; 
 W is NR 3 R 4 ; 
 R p  is hydrogen, hydroxy protecting group or hydroxy prodrug group; and 
 B is independently selected from hydrogen, acyl, silane, a substituted or unsubstituted, saturated or unsaturated aliphatic group, a substituted or unsubstituted, saturated or unsaturated alicyclic group, a substituted or unsubstituted aromatic group, a substituted or unsubstituted heteroaromatic group, or a substituted or unsubstituted heterocyclic group. 
 
   
   
       15 . A compound according to  claim 14  represented by Formula VII: 
     
       
         
         
             
             
         
       
     
   
   
       16 . A pharmaceutical composition comprising a compound of  claim 14  or a pharmaceutically acceptable salt, ester or prodrug thereof, in combination with a pharmaceutically acceptable carrier. 
   
   
       17 . A method of treating a bacterial infection in a subject in need of such treatment comprising, administering to said subject a pharmaceutical composition of  claim 16 . 
   
   
       18 . A method of treating inflammation in a subject in need of such treatment comprising, administering to said subject a pharmaceutical composition of  claim 16 . 
   
   
       19 . A method of treating cystic fibrosis in a subject in need of such treatment comprising, administering to said subject a pharmaceutical composition of  claim 16 .