ANTIBACTERIAL COMPOUNDS AND METHODS FOR USE

摘要

The present description relates to compounds and forms and pharmaceutical compositions thereof and methods for use thereof to treat or ameliorate bacterial infections caused by wild-type and multi-drug resistant Gram-negative and Gram-positive pathogens.

主权项

1. A compound of Formula (I), Formula (II) or Formula (III): or a form thereof, wherein X is a bond, N(R14), S, O, —CH(R9)—, —CH(R9)—CH(R10)—, —CH(R9)—CH(R10)—CH(R11)—, —C(R9)═C(R10)—, —C(R9)═C(R10)—CH(R11)—, —CH(R9)—C(R10)═C(R11)—, —O—CH(R10)—, —CH(R9)—O—, —N(R14)—CH(R10)—, —CH(R9)—N(R14)—, —S—CH(R10)—, —CH(R9)—S—, —O—CH(R10)—CH(R11)—, —CH(R9)—O—CH(R11)—, —CH(R9)—CH(R10)—O—, —N(R14)—CH(R10)—CH(R11)—, —CH(R9)—N(R14)—CH(R11)—, —CH(R9)—CH(R10)—N(R14)—, —S—CH(R10)—CH(R11)—, —CH(R9)—S—CH(R11)—, —CH(R9)—CH(R10)—S—; —O—C(O)—CH(R11)—, —C(O)—O—CH(R11)—, —CH(R9)—O—C(O)—, —CH(R9)—C(O)—O—, —N(R14)—C(O)—CH(R11)—, —C(O)—N(R14)—CH(R11)—, —CH(R9)—N(R14)—C(O)—, —CH(R9)—C(O)—N(R14)—, —S—C(O)—CH(R11)—, —C(O)—S—CH(R11)—, —CH(R9)—S—C(O)— or —CH(R9)—C(O)—S—; Y1 is —N(R12)— or —O—; Y2 is —C(R13)—, —N(R12)— or —O—; wherein the dashed line represents a double bond that is present when Y2 is —C(R13)— and absent when Y2 is —N(R12)— or —O—; Z is N(R14), S, O, C(O) or —CH(R3)—; R1 is hydrogen, halogen, hydroxyl, oxo, cyano, nitro, C1-8alkyl, hydroxyl-C1-8alkyl, halo-C1-8alkyl, C1-8alkoxy, halo-C1-8alkoxy, C1-8alkyl-thio, carboxyl, C1-8alkyl-carbonyl, C1-8alkoxy-carbonyl, amino-carbonyl, amino, C1-8alkyl-amino, (C1-8alkyl)2-amino, C2-8alkenyl-amino, (C2-8alkenyl)2-amino, C2-8alkynyl-amino, (C2-8alkynyl)2-amino, amino-C1-8alkyl, C1-10alkyl-amino-C1-8alkyl, (C1-8alkyl)2-amino-C1-8alkyl, C2-8alkenyl-amino-C1-8alkyl, (C2-8alkenyl)2-amino-C1-8alkyl, C2-8alkynyl-amino-C1-8alkyl, (C2-8alkynyl)2-amino-C1-8alkyl, halo-C1-8alkyl-amino, (halo-C1-8alkyl)2-amino, halo-C1-8alkyl-amino-C1-8alkyl, (halo-C1-8alkyl)2-amino-C1-8alkyl, C1-8alkoxy-C1-8alkyl-amino, (C1-8alkoxy-C1-8alkyl, C1-8alkyl)-amino, (C1-8alkoxy-C1-8alkyl)2-amino, C1-8alkoxy-C1-8alkyl-amino-C1-8alkyl, (C1-8alkoxy-C1-8alkyl, C1-8alkyl)-amino-C1-8alkyl, (C1-8alkoxy-C1-8alkyl)2-amino-C1-8alkyl, amino-C1-8alkyl-amino, (amino-C1-8alkyl, C1-8alkyl)amino, C1-8alkyl-amino-C1-8alkyl-amino, (C1-8alkyl-amino-C1-8alkyl, C1-8alkyl)amino, (C1-8alkyl)2-amino-C1-8alkyl-amino, [(C1-8alkyl)2-amino-C1-8alkyl, C1-8alkyl]amino, amino-C1-8alkyl-amino-C1-8alkyl, (amino-C1-8alkyl, C1-18alkyl)amino-C1-8alkyl, C1-8alkyl-amino-C1-8alkyl-amino-C1-8alkyl, (C1-8alkyl-amino-C1-8alkyl, C1-8alkyl)amino-C1-8alkyl, (C1-8alkyl)2-amino-C1-8alkyl-amino-C1-8alkyl, [(C1-8alkyl)2-amino-C1-8alkyl, C1-8-alkyl]amino-C1-8alkyl, hydroxyl-amino, hydroxyl-C1-8alkyl-amino, (hydroxyl-C1-8alkyl, C1-8alkyl)amino, (hydroxyl-C1-8alkyl)2-amino, hydroxyl-C1-8alkyl-amino-C1-8alkyl, (hydroxyl-C1-8alkyl, C1-8alkyl)amino-C1-8alkyl, hydroxyl-C1-8alkyl-amino-C1-8alkyl-amino, (hydroxyl-C1-8alkyl-amino-C1-8alkyl, C1-8alkyl)amino, (hydroxyl-C1-18alkyl, C1-8alkyl)amino-C1-8alkyl-amino, [(hydroxyl-C1-8alkyl, C1-8alkyl)amino-C1-8alkyl, C1-8alkyl]amino, (C1-8alkyl-carbonyl, C1-8alkyl)amino-C1-8alkyl, C1-8alkyl-amino-carbonyl, (C1-8alkyl)2-amino-carbonyl, (C1-8alkyl)2-amino-carbonyl-C1-8alkyl-amino-C1-8alkyl, C3-14cycloalkyl, C3-14cycloalkyl-C1-8alkyl, C3-14cycloalkyl-oxy, C3-14cycloalkyl-C1-8alkoxy, C3-14cycloalkyl-amino, C3-14cycloalkyl-amino-C1-8alkyl, (C3-14cycloalkyl, C1-8alkyl)amino-C1-8alkyl, (C3-14cycloalkyl)2-amino-C1-8alkyl, C3-14cycloalkyl-C1-8alkyl-amino-C1-8alkyl, (C3-14cycloalkyl-C1-8alkyl, C1-8alkyl)amino-C1-8alkyl, (C3-14cycloalkyl-C1-8alkyl)2-amino-C1-8alkyl, aryl, aryl-C1-8alkyl, aryl-amino, (aryl, C1-8alkyl)amino, (aryl)2-amino, aryl-amino-C1-8alkyl, (aryl, C1-8alkyl)amino-C1-8alkyl, (aryl)2-amino-C1-8alkyl, aryl-C1-8alkyl-amino, (aryl-C1-8alkyl, C1-8alkyl)amino, (aryl-C1-8alkyl)2-amino, aryl-C1-8alkyl-amino-C1-8alkyl, (aryl-C1-8alkyl, C1-8alkyl)amino-C1-8alkyl, (aryl-C1-8alkyl)2-amino-C1-8alkyl, heteroaryl, heteroaryl-C1-8alkyl, heteroaryl-amino, heteroaryl-C1-8alkyl-amino, (heteroaryl-C1-8alkyl, C1-8alkyl)amino, (heteroaryl-C1-8alkyl)2-amino, heteroaryl-C1-8alkyl-amino-C1-8alkyl, (heteroaryl-C1-8alkyl, C1-8alkyl)amino-C1-8alkyl, heterocyclyl, heterocyclyl-C1-8alkyl, heterocyclyl-oxy, heterocyclyl-C1-8alkoxy, heterocyclyl-amino, (heterocyclyl, C1-8alkyl)amino, (heterocyclyl)2-amino, heterocyclyl-amino-C1-8alkyl, (heterocyclyl, C1-8alkyl)amino-C1-8alkyl, (heterocyclyl)2-amino-C1-8alkyl, (heterocyclyl, C3-14cycloalkyl-C1-8alkyl)amino-C1-8alkyl, heterocyclyl-C1-8alkyl-amino-C1-8alkyl, (heterocyclyl-C1-8alkyl, C1-8alkyl)amino-C1-8alkyl, (heterocyclyl-C1-8alkyl)2-amino-C1-8alkyl, heterocyclyl-oxy-amino, (heterocyclyl-oxy, C1-8alkyl)amino, (heterocyclyl-oxy)2-amino, (heterocyclyl-oxy-C1-8alkyl, C1-8alkyl)amino, heterocyclyl-carbonyl or heterocyclyl-carbonyl-oxy; wherein each instance of C3-14cycloalkyl, aryl, heterocyclyl and heteroaryl is optionally substituted with one, two or three substituents each selected from R15; and, wherein each instance of aryl, heterocyclyl or heteroaryl is optionally substituted with one additional substituent selected from R16; R2 is hydrogen, halogen, hydroxyl, C1-8alkyl, amino, C1-8alkyl-amino or (C1-8alkyl)2-amino; R3 is hydrogen, halogen, hydroxyl, C1-8alkyl, amino, C1-8alkyl-amino or (C1-8alkyl)2-amino; R4 is hydrogen, hydroxyl, C1-8alkyl, aryl-C1-8alkyl, wherein aryl is optionally substituted with one additional substituent selected from C1-8alkyl, halo-C1-8alkyl, C1-8alkoxy or C1-8alkoxy-C1-8alkyl; R5 is hydrogen, halogen, hydroxyl, C1-8alkyl, C1-8alkoxy, carboxyl, amino, C1-8alkyl-amino, (C1-8alkyl)2-amino or C1-8alkyl-SO2-amino; R6 is hydrogen or C1-8alkyl; R7 is hydrogen, halogen, hydroxyl, C1-8alkyl, amino, C1-8alkyl-amino or (C1-8-alkyl)2-amino; R8 is hydrogen, halogen, hydroxyl, C1-8alkyl, amino, C1-8alkyl-amino or (C1-8alkyl)2-amino; R9 is hydrogen, halogen, hydroxyl, C1-8alkyl, amino, C1-8alkyl-amino or (C1-8alkyl)2-amino; R10 is hydrogen, halogen, hydroxyl, C1-8alkyl, amino, C1-8alkyl-amino or (C1-8alkyl)2-amino; R11 is hydrogen, halogen, hydroxyl, C1-8alkyl, amino, C1-8alkyl-amino or (C1-8alkyl)2-amino; R12 is hydrogen, C1-8alkyl, aryl or heteroaryl, wherein aryl and heteroaryl is optionally substituted with one additional substituent selected from C1-8alkyl, halo-C1-8alkyl, C1-8alkoxy or C1-8alkoxy-C1-8alkyl; R13 is hydrogen, cyano, halogen, hydroxyl or C1-8alkyl; R14 is hydrogen, C1-8alkyl, C1-8alkyl-carbonyl, C1-8alkoxy-carbonyl, aryl or heteroaryl, wherein aryl and heteroaryl is optionally substituted with one additional substituent selected from C1-8alkyl, halo-C1-8alkyl, C1-8alkoxy or C1-8alkoxy-C1-8alkyl; R15 is azido, halogen, hydroxyl, cyano, nitro, C1-8alkyl, halo-C1-8alkyl, hydroxyl-C1-8alkyl, C1-8alkoxy-C1-8alkyl, C1-8alkoxy, halo-C1-8alkoxy, hydroxyl-C1-8alkoxy, carboxyl, C1-8alkyl-carbonyl, C1-8alkoxy-carbonyl, amino, C1-8alkyl-amino, (C1-8alkyl)2-amino, halo-C1-8alkyl-amino, (halo-C1-8alkyl)2-amino, halo-C1-8alkyl-amino-C1-8alkyl, (halo-C1-8alkyl)2-amino-C1-8alkyl, amino-C1-8alkyl, C1-8alkyl-amino-C1-8alkyl, (C1-8alkyl)2-amino-C1-8alkyl, [(C1-8alkyl)2-amino-C1-8alkyl, C1-8alkyl]amino-C1-8alkyl C1-8alkyl-thio, amino-carbonyl, C1-8alkyl-amino-carbonyl, (C1-8alkyl)2-amino-carbonyl, C1-8alkyl-carbonyl-amino or (carboxyl-C1-8alkyl, C1-8alkyl)amino-carbonyl-amino; R16 is C3-14cycloalkyl, C3-14cycloalkyl-amino, aryl, aryl-C1-8alkyl, aryl-amino, (aryl, C1-8alkyl)amino, (aryl)2-amino, aryl-C1-8alkyl-amino, (aryl-C1-8alkyl, C1-8alkyl)amino, (aryl-C1-8alkyl)2-amino, aryl-C1-8alkyl-amino-C1-8alkyl, (aryl-C1-8alkyl, C1-8alkyl)amino-C1-8alkyl, (aryl-C1-8alkyl)2-amino-C1-8alkyl, aryl-amino-C1-8alkyl, (aryl, C1-8alkyl)amino-C1-8alkyl, (aryl)2-amino-C1-8alkyl, aryl-amino-carbonyl, aryl-C1-8alkoxy, aryl-C1-8alkoxy-carbonyl-amino, heteroaryl, heteroaryl-C1-8alkyl, heteroaryl-amino, (heteroaryl)2-amino, heteroaryl-C1-8alkyl-amino, (heteroaryl-C1-8alkyl, C1-8alkyl)amino, (heteroaryl-C1-8alkyl)2-amino, heteroaryl-C1-8alkyl-amino-C1-8alkyl, (heteroaryl-C1-8alkyl, C1-8alkyl)amino-C1-8alkyl, (heteroaryl-C1-8alkyl)2-amino-C1-8alkyl, heterocyclyl, heterocyclyl-C1-8alkyl, heterocyclyl-amino-C1-8alkyl or heterocyclyl-oxy; wherein each instance of C3-14cycloalkyl is optionally substituted with one substituent selected from R18; and, wherein each instance of aryl is optionally substituted with one substituent selected from R19; R17 is azido, halogen, hydroxyl, cyano, nitro, C1-8alkyl, halo-C1-8alkyl, C1-8alkoxy, C1-8alkoxy-C1-8alkyl, halo-C1-8alkoxy, carboxyl, C1-8alkoxy-carbonyl, amino, C1-8alkyl-amino, (C1-8alkyl)2-amino, C1-8alkyl-thio, aryl, aryl-C1-8alkoxy, heteroaryl, heterocyclyl, heterocyclyl-C1-8alkyl or heterocyclyl-oxy; R18 is amino, C1-8alkyl-amino, (C1-8alkyl)2-amino, amino-C1-8alkyl, C1-8alkyl-amino-C1-8alkyl, (C1-8alkyl)2-amino-C1-8alkyl or aryl-C1-8alkyl-amino; and, R19 is halogen.