Antibacterial agents

Abstract

Antibacterial compounds of formula I are provided: As well as stereoisomers, pharmaceutically acceptable salts, esters, and prodrugs thereof; pharmaceutical compositions comprising such compounds; methods of treating bacterial infections by the administration of such compounds; and processes for the preparation of the compounds.

1 . A compound according to the formula IA:  
       
         
           
           
               
               
           
         
         or a stereoisomer, pharmaceutically acceptable salt, ester, or prodrug thereof, wherein  
         D is absent or selected from the group consisting of 
 (1) substituted or unsubstituted C 3 -C 8 -cycloalkyl;  
 (2) substituted or unsubstituted aryl;  
 (3) substituted or unsubstituted heterocyclyl; and  
 (4) substituted or unsubstituted heteroaryl;  
 
         Y is selected from the group consisting of 
 (1) substituted or unsubstituted C 3 -C 8 -cycloalkyl;  
 (2) substituted or unsubstituted aryl;  
 (3) substituted or unsubstituted heterocyclyl; and  
 (4) substituted or unsubstituted heteroaryl;  
 
         R 4  is H or substituted or unsubstituted C 1 -C 6 -alkyl;  
         A is selected from the group consisting of 
 (1) —C(R 1a ,R 2a )OR 3a ; and  
 (2) —C(R 1a ,R 2a )N(R 4a ,R 5a ); 
 wherein R 1a , R 2a , R 4a , and R 5a  are independently selected from the group consisting of  
 
 (1) H; and  
 (2) substituted and unsubstituted C 1 -C 6 -alkyl.  
 
       
     
     
         2 . The compound of  claim 1 , wherein A is —C(R 1a ,R 2a )OR 3a .  
     
     
         3 . The compound of  claim 2 , wherein A is —CH 2 OH.  
     
     
         4 . The compound of  claim 2 , wherein A is —CH(CH 3 )OH.  
     
     
         5 . The compound of  claim 1 , wherein A is —C(R 1a ,R 2a )N(R 4a ,R 5a ).  
     
     
         6 . The compound of  claim 5 , wherein A is —CH(CH 3 )NH 2 .  
     
     
         7 . The compound of  claim 1 , wherein D is absent and Y is a substituted or unsubstituted aryl.  
     
     
         8 . The compound of  claim 1 , wherein D is a substituted or unsubstituted aryl and Y is a substituted or unsubstituted aryl.  
     
     
         9 . A compound according to the formula IB:  
       
         
           
           
               
               
           
         
         or a stereoisomer, pharmaceutically acceptable salt, ester, or prodrug thereof, wherein  
         D is absent or selected from the group consisting of 
 (1) substituted or unsubstituted C 3 -C 8 -cycloalkyl;  
 (2) substituted or unsubstituted aryl;  
 (3) substituted or unsubstituted heterocyclyl; and  
 (4) substituted or unsubstituted heteroaryl;  
 
         G is —C≡C—C≡C—;  
         Y is selected from the group consisting of 
 (1) substituted or unsubstituted C 3 -C 8 -cycloalkyl;  
 (2) substituted or unsubstituted aryl;  
 (3) substituted or unsubstituted heterocyclyl; and  
 (4) substituted or unsubstituted heteroaryl;  
 
         R 4  is H or substituted or unsubstituted C 1 -C 6 -alkyl;  
         A is —C(R 1a ,R 2a )N(R 4a ,R 5a ), wherein R 1a , R 2a , R 4a , and R 5a  are independently selected from the group consisting of 
 (1) H; and  
 (2) substituted and unsubstituted C 1 -C 6 -alkyl.  
 
       
     
     
         10 . A pharmaceutical composition comprising the compound of  claim 1  and a pharmaceutically acceptable excipient.  
     
     
         11 . A pharmaceutical composition comprising the compound of  claim 9  and a pharmaceutically acceptable excipient.  
     
     
         12 . A pharmaceutical composition comprising a compound of  claim 1 , a second agent, and a pharmaceutically acceptable excipient, wherein the second agent is an antibacterial agent, and antiendotoxin agent or an inhaled non-antibacterial agent for the treatment of respiratory tract infection.  
     
     
         13 . A pharmaceutical composition comprising a compound of  claim 9 , a second agent, and a pharmaceutically acceptable excipient, wherein the second agent is an antibacterial agent, and antiendotoxin agent or an inhaled non-antibacterial agent for the treatment of respiratory tract infection.  
     
     
         14 . A method of inhibiting LpxC comprising administering to a patient in need thereof, an effective amount of the compound of  claim 1 .  
     
     
         15 . A method of inhibiting LpxC comprising administering to a patient in need thereof, an effective amount of the compound of  claim 9 .  
     
     
         16 . A method of inhibiting LpxC comprising administering to a patient in need thereof, an effective amount of the compound of  claim 1  and an effective amount of a second agent, wherein the second agent is an antibacterial agent, an antiendotoxin agent or an inhaled non-antibacterial agent for the treatment of respiratory tract infection.  
     
     
         17 . A method of inhibiting LpxC comprising administering to a patient in need thereof, an effective amount of the compound of  claim 9  and an effective amount of a second agent, wherein the second agent is an antibacterial agent, an antiendotoxin agent or an inhaled non-antibacterial agent for the treatment of respiratory tract infection.  
     
     
         18 . A method of treating an infection comprising administering to a patient in need thereof, an effective amount of the compound of  claim 1 .  
     
     
         19 . A method of treating an infection comprising administering to a patient in need thereof, an effective amount of the compound of  claim 9 .  
     
     
         20 . A method of treating an infection comprising administering to a patient in need thereof, an effective amount of the compound of  claim 1  and an effective amount of a second agent, wherein the second agent is an antibacterial agent, an antiendotoxin agent or an inhaled non-antibacterial agent for the treatment of respiratory tract infection.  
     
     
         21 . A method of treating an infection comprising administering to a patient in need thereof, an effective amount of the compound of  claim 9  and an effective amount of a second agent, wherein the second agent is an antibacterial agent, an antiendotoxin agent or an inhaled non-antibacterial agent for the treatment of respiratory tract infection.