Antipathogenic benzamide compounds

Abstract

Antipathogenic benzamide compounds having the formula wherein at least one of the R 1 groups is F, Cl, CN or CF 3 and R 2 , R 3 , Y, Z, m, and n are as defined herein.

What is claimed is:  
     
         1 . A compound according to the formula  
       
         
           
           
               
               
           
         
       
       and the pharmaceutically acceptable salts thereof, 
 wherein 
 each R 1  is independently H, F, Cl, CN, CF 3 , OH, N(R 2 ) 2 , OR 2  or a substituted or unsubstituted (C 1 -C 12 )alkyl group, or a substituted or unsubstituted (C 1 -C 12 )heteroalkyl group, with the proviso that at least one R 1  is F, Cl, CN, OCF 3 , OCF 2 H, or CF 3;    
 each R 2  and R 3  is independently H, a substituted or unsubstituted (C 1 -C 12 )alkyl group, or a substituted or unsubstituted (C 1 -C 12 )heteroalkyl group;  
 m is an integer from 1 to 25, inclusive;  
 each Y is independently a branched or unbranched, substituted or unsubstituted (C 1 -C 5 )alkylene group or a substituted or unsubstituted, aromatic or heteroaromatic ring system, wherein the ring system has at least one of a 5- or 6-member aromatic or heteroaromatic ring or fused 6,6 or 6,5 aromatic or heteroaromatic rings, with the proviso that at least one Y is a substituted or unsubstituted 5-member hetero-aromatic ring;  
 Z is O or N; and  
 n is 1 if Z is O and 2 if Z is N;  
 said compound having at least one basic group having a pK b  of 12 or less or a quaternized nitrogen group.  
 
 
     
     
         2 . A compound of the formula  
       
         
           
           
               
               
           
         
       
       and the pharmaceutically acceptable salts thereof, 
 wherein 
 m is an integer from 1 to 25, inclusive;  
 each moiety —(NR 3 —Y—CO)— is independently selected from the group consisting of 
 (a) moieties M 1  having the formula  
                     
  wherein one of X 1 , X 2 , and X 3  is a ring vertex selected from the group consisting of —O—, —S—, and —NR 2 —, and the other two of X 1 , X 2 , and X 3  are ring vertices selected from the group consisting of ═N— and ═CR 4 —;  
 (b) moieties M2 having the formula  
                     
  wherein x is 0 or 1 and each R 15  is independently H, OH, NH 2 , or F;  
 (c) moieties M 3  having the formula  
                     
  wherein each L is independently a divalent moiety separating —NH— and —(C═O)— by 3 or 4 atoms; and  
 (d) moieties M 4  having the formula  
                     
 
 with the proviso that at least one moiety —(NR 3 —Y—CO)— is a moiety M 1 ;  
 Z is O or N;  
 n is 1 if Z is O and 2 if Z is N;  
 each R 1  is independently H, F, Cl, CN, CF 3 , OH, N(R 2 ) 2 , OR 2  or a substituted or unsubstituted (C 1 -C 12 )alkyl group, or a substituted or unsubstituted (C 1 -C 12 )heteroalkyl group, with the proviso that at least one R 1  is F, Cl, CN or CF 3 ;  
 each R 2  and R 3  is independently H, a substituted or unsubstituted (C 1 -C 12 )alkyl group, or a substituted or unsubstituted (C 1 -C 12 )heteroalkyl group;  
 each R 4  is independently H, F, Cl, Br, I, CN, OH, NO 2 , NH 2 , a substituted or unsubstituted (C 1 -C 12 )alkyl group, or a substituted or unsubstituted (C 1 -C 12 )heteroalkyl group;  
 said compound having at least one basic group having a pK b  of 12 or less or a quaternized nitrogen group.  
 
 
     
     
         3 . A compound according to  claim 2 , wherein the residue Z(R 2 ) n  contains a basic group having a pK b  of 12 or less or a quaternized nitrogen group.  
     
     
         4 . A compound according to  claim 2 , wherein an R 3  contains a basic group having a pK b  of 12 or less or a quaternized nitrogen group.  
     
     
         5 . A compound according to  claim 2 , wherein an R 1  contains a basic group having a pK b  of 12 or less or a quaternized nitrogen group.  
     
     
         6 . A compound according to  claim 2 , wherein a moiety M 1  or M 4  contains a basic group having a pK b  of 12 or less or a quaternized nitrogen group.  
     
     
         7 . A compound according to  claim 2 , wherein  
       
         
           
           
               
               
           
         
       
       is selected from the group consisting of  
       
         
           
           
               
               
           
         
       
     
     
         8 . A compound according to  claim 2 , having the formula  
       
         
           
           
               
               
           
         
       
       wherein each A is independently M 1  or M 4 ; M 1 , M 2 , M 3 , M 4 , R 1 , R 2 , Z and n have the meanings assigned in  claim 2;  each of a, c, e, g and h is an integer independently from 0 to 4, inclusive; and each of b, d, and f is independently 0 or 1, with the proviso that at least one A is M 1 .  
     
     
         9 . A compound according to  claim 2 , having the formula  
       
         
           
           
               
               
           
         
       
       wherein X 1 , X 2 , X3, R 1 , R 2 , R 3 , Z, and n have the meanings assigned in  claim 2  and i is an integer from 1 to 4, inclusive.  
     
     
         10 . A compound according to  claim 9 , having the formula  
       
         
           
           
               
               
           
         
       
       wherein R 1 , R 2 , i, Z and n have the meanings assigned in  claim 9 .  
     
     
         11 . A compound according to  claim 9 , having the formula  
       
         
           
           
               
               
           
         
       
       wherein R 1 , R 2 , i, Z and n have the meanings assigned in  claim 9 .  
     
     
         12 . A compound according to  claim 9 , having the formula  
       
         
           
           
               
               
           
         
       
       wherein R 1 , R 2 , i, Z, and n are have the meanings assigned in  claim 9 , with the proviso that at least one R 2  bonded to a pyrrole nitrogen is other than CH 3 .  
     
     
         13 . A compound according to  claim 12 , wherein at least one R 2  bonded to a pyrrole nitrogen contains a basic group having a pK b  of 12 or less or a quaternized nitrogen group.  
     
     
         14 . A compound according to  claim 9 , wherein at least one moiety  
       
         
           
           
               
               
           
         
       
       is other than pyrrole.  
     
     
         15 . A compound according to  claim 9 , wherein the moiety  
       
         
           
           
               
               
           
         
       
       which is other than pyrrole is selected from the group consisting of  
       
         
           
           
               
               
           
         
       
       wherein R 2  is as defined in base  claim 2 .  
     
     
         16 . A compound according to  claim 2 , having the formula  
       
         
           
           
               
               
           
         
       
       wherein M 1 , M 4  , R 1 , R 2 , Z, and n are as defined in  claim 2  and each k is independently an integer from 0 to 4, inclusive, with the proviso that at least one k is not 0.  
     
     
         17 . A method of treating a bacterial infection in a mammal, comprising administering to a patient in need of such treatment an effective amount of a compound according to  claim 1 .  
     
     
         18 . A method according to  claim 17 , wherein the bacterial infection is an infection by Gram-positive bacteria.  
     
     
         19 . A method according to  claim 17 , wherein the bacterial infection is an infection by drug resistant bacteria.  
     
     
         20 . A method according to  claim 19 , wherein the drug resistant bacteria is MRSA, MRSE, PRSP, or VRE.  
     
     
         21 . A method of treating a bacterial infection in a mammal, comprising administering to a patient in need of such treatment an effective amount of a compound according to  claim 2 .  
     
     
         22 . A method according to  claim 21 , wherein the bacterial infection is an infection by Gram-positive bacteria.  
     
     
         23 . A method according to  claim 21 , wherein the bacterial infection is an infection by drug resistant bacteria.  
     
     
         24 . A method according to  claim 23 , wherein the drug resistant bacteria is MRSA, MRSE, PRSP, or VRE.  
     
     
         25 . The use of a compound according to  claim 1  for the preparation of a medicament for the treatment of a bacterial infection in a mammal.  
     
     
         26 . The use of a compound according to  claim 2  for the preparation of a medicament for the treatment of a bacteria infection in a mammal.