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