ISOXAZOLE HYDROXAMIC ACID COMPOUNDS AS LpxC INHIBITORS

摘要

This invention pertains generally to compounds of Formula I as described herein and compositions containing such compounds, as well as methods of using such compounds to treat bacterial infections. In certain aspects, the invention provides methods and compositions comprising these compounds for treating infections caused by Gram-negative bacteria.;

主权项

1. A compound of Formula (I): or a pharmaceutically acceptable salt thereof, wherein:
X is —NH—, and R1 is —CH(OH)—Y;orX is —CH2—, and R1 is —CH(OH)—Y or —SO2R2 where R2 is C1-C3 alkyl;R3 is H or halo;Y is selected from a 5-membered heteroaryl ring containing 1-3 heteroatoms selected from N, O and S as ring members, phenyl, and C1-3 alkyl, and each Y is optionally substituted with one to three R4;
each R4 is independently selected from halo, C1-3 alkyl, and C3-6 cycloalkyl, wherein the C1-3 alkyl and C3-6 cycloalkyl are each optionally substituted with up to three groups selected from halo, CN and —OH;L is —C═C— or —CR5═CR5—;R5 is independently selected at each occurrence from H, halo and methyl;andZ is selected from C1-6 alkyl, C3-C6 cycloalkyl, pyridinyl, and phenyl, each of which is optionally substituted with up to three groups selected from halogen, hydroxy, C1-4 alkoxy, C1-4 haloalkoxy, CN, and C1-4 alkyl that is optionally substituted with one to three groups selected from halogen, hydroxy, amino, CN, and C1-3 alkoxy;or, when L is —CR5═CR5—, Z taken together with one of the R5 groups and any atoms connecting Z with the R5 group can form a 3-7 membered cycloalkyl or cycloalkenyl group that is optionally substituted with up to three groups selected from halogen, hydroxy, C1-4 alkoxy, C1-4 haloalkoxy, CN, and C1-4 alkyl that is optionally substituted with one to three groups selected from halogen, hydroxy, amino, CN, and C1-3 alkoxy.