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 having the formula XIII:
or a stereoisomer, pharmaceutically acceptable salt, ester, or prodrug thereof, wherein R 4 is selected from the group consisting of
(1) H,
(2) substituted or unsubstituted C i -C 6 -alkyl,
(3) C 1 -C 6 -alkyl substituted with aryl,
(4) C 1 -C 6 -alkyl substituted with heterocyclyl, and
(5) C 1 -C 6 -alkyl substituted with heteroaryl;
A is H or —CH(CH 3 )OH;
R 1 is H or substituted or unsubstituted C 1-6 -alkyl;
R 2 is selected from the group consisting of
(1) H,
(2) substituted or unsubstituted C 1 -C 6 -alkyl,
(3) substituted or unsubstituted aryl,
(4) substituted or unsubstituted heterocyclyl,
(5) substituted or unsubstituted heteroaryl,
(6) C 1 -C 6 -alkyl substituted with aryl,
(7) C 1 -C 6 -alkyl substituted with heterocyclyl,
(8) C 1 -C 6 -alkyl substituted with heteroaryl,
or R 1 and R 2 together with the N atom to which they are attached can form a substituted or unsubstituted heterocyclic ring, having from 3 to 10 ring atoms, wherein 1-2 ring atoms of the heterocyclic ring system are selected from N, O and S.
2. The compound of claim 1 , wherein R 4 is H.
3. The compound of claim 1 , wherein A is —CH(CH 3 )OH.
4. The compound of claim 1 , wherein R 1 is H.
5. The compound of claim 1 , wherein R 1 is H and R 2 is substituted or unsubstituted heterocyclyl or C 1 -C 6 -alkyl substituted with heterocyclyl, wherein the heterocyclyl group is selected from the group consisting of pyridine, pyrrolidine, thienyl and piperidine.
6. The compound of claim 1 , wherein R 1 and R 2 together with the N atom to which they are attached can form a substituted or unsubstituted heterocyclic ring selected from the group consisting of morpholine, piperazine, piperidine and pyrrolidine.
7. A pharmaceutical composition comprising the compound of claim 1 and a pharmaceutically acceptable excipient.
8. A pharmaceutical composition comprising the 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 method of inhibiting LpxC comprising administering to a patient in need thereof, an effective amount of the compound of claim 1 .
10. 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.