Antibiotic ammonium compounds and methods for the treatment of bacterial infections

A compound according to Formula I:

• wherein
• A is a pharmaceutically acceptable anion;
• Y is selected from the group consisting of —NR7SO2—, —OC(O)—, and —NR7C(O)—;
• Z is C1-6 alkylene;
• R1 is selected from the group consisting of C1-18 alkyl, C3-8 cycloalkyl, C6-10 aryl, 3- to 10-membered heterocyclyl, 5- to 10-membered heteroaryl, and -L1-R1a;
• L1 is C1-6 alkylene;
• R1a is selected from the group consisting of C3-8 cycloalkyl, C6-10 aryl, 3- to 10-membered heterocyclyl, and 5- to 10-membered heteroaryl;
• R2 is selected from the group consisting of H, C1-18 alkyl, C3-8 cycloalkyl, C6-10 aryl, 3- to 10-membered heterocyclyl, 5- to 10-membered heteroaryl, and -L2-R2a;
• R3 is selected from the group consisting of H, C1-18 alkyl, C3-8 cycloalkyl, C6-10 aryl, 3- to 10-membered heterocyclyl, 5- to 10-membered heteroaryl, and -L2-R2a;
• L2 is C1-6 alkylene;
• R2a is selected from the group consisting of C3-8 cycloalkyl, C6-10 aryl, 3- to 10-membered heterocyclyl, and 5- to 10-membered heteroaryl;
• R2 and R3 are optionally taken together with the nitrogen to which they are attached to form 3- to 10-membered heterocyclyl;
• one of R2 and R3 is optionally taken together with the nitrogen to which it is attached and Y or Z to form 3- to 10-membered heterocyclyl;
• R4a is selected from the group consisting of H, C1-18 alkoxy, C1-18 alkyl, C1-18 haloalkyl, C1-18 alkenyl, halogen, —OH, —COOH, —N(R7)2, —NO2, —SO3, —SO2N(R7)2, and -L4-R4x;
• R4c is selected from the group consisting of halogen, H, C1-18 alkoxy, C1-18 alkyl, C1-18 haloalkyl, C1-18 alkenyl, —OH, —COOH, —N(R7)2, —NO2, —SO3, —SO2N(R7)2, and -L4-R4x;
• R4b, R4d, and R4c are independently selected from the group consisting of H, C1-18 alkoxy, C1-18 alkyl, C1-18 haloalkyl, C1-18 alkenyl, halogen, —OH, —COOH, —N(R7)2, —NO2, —SO3, —SO2N(R7)2, and -L4-R4x;
• L4 is selected from the group consisting of C1-6 alkylene, 2- to 6-membered heteroalkylene, and —O—;
• R4x is selected from the group consisting of C3-8 cycloalkyl, C6-10 aryl, 3- to 10-membered heterocyclyl, and 5- to 10-membered heteroaryl;
• R5a and R5b are independently selected from the group consisting of H, C1-18 alkoxy, C1-18 alkyl, C1-18 haloalkyl, C1-18 alkenyl, halogen, —OH, —COOH, —N(R7)2, —NO2, —SO3, —SO2N(R7)2, and -L5-R5x;
• L5 is selected from the group consisting of C1-6 alkylene, 2- to 6-membered heteroalkylene, and —O—;
• R5x is selected from the group consisting of C3-8 cycloalkyl, C6-10 aryl, 3- to 10-membered heterocyclyl, and 5- to 10-membered heteroaryl;
• R6 is selected from the group consisting of H, C1-6 alkyl, and C2-7 acyl;
• R6 is optionally taken together with R4a or R4c to form a 5-to- 8-membered ring;
• each R7 is independently selected from the group consisting of H, C1-6 alkyl, and C2-7 acyl;
• each C3-8 cycloalkyl, C6-10 aryl, 3- to 10-membered heterocyclyl, and 5- to 10-membered heteroaryl is optionally and independently substituted with one or more substituents selected from the group consisting of C1-18 alkyl, C1-18 haloalkyl, C1-18 alkenyl, C1-18 alkoxy, halogen, —OH, —C(O)R8, —C(O)N(R7)2, —N(R7)2, —NO2, —SO3, and —SO2N(R7)2;
• and
• each R8 is independently selected from the group consisting of C1-6 alkyl, C1-6 alkoxy, and —OH;
• provided that at least one of R4a, R4b, R4c, R4d, and R4c is C7-18 alkoxy or C4-6 alkoxy;
• provided that if Y is —OC(O)—, Z is ethylene (—(CH2)2—), R1 is methyl, and R2 and R3 are ethyl, then at least two of R4a, R4b, R4c, R4d, and R4c are other than H;
• and
• provided that the compound is other than:
• an N,N-diethyl-N-methyl-2-(4-(2-(octyloxy)benzamido)benzamido)ethan-1-aminium species,
• an N,N,N-trimethyl-2-((4-(2-(octyloxy)benzamido)benzoyl)oxy)ethan-1-aminium species,
• an N,N,N-trimethyl-2-((4-(4-(isopentyloxy)benzamido)benzoyl)oxy)ethan-1-aminium species,
• an N,N,N-trimethyl-2-((4-(4-(isopentyloxy)benzamido)benzoyl)oxy)propan-1-aminium species,
• an 1-methyl-1-(2-4-(2-(octyloxy)benzamido)benzoyl)oxy)ethyl)piperidin-1-ium species, or
• 4-methyl-4-(2-((4-(2-(octyloxy)benzamido)benzoyl)oxy)ethyl)morpholin-4-ium bromide.