Antibiotic compounds

A compound of formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, isomer, tautomer, N-oxide, ester, isotope or protected form thereof:

• wherein R1 is selected from hydrogen and C1-4alkyl;
• Ar1 is selected from any one of the following ring systems:
• wherein R2 is present, and is one or more substituents each independently selected from halogen, cyano, hydroxyl, hydroxylC1-4alkyl, C1-4alkyl, haloC1-4alkyl, C1-4alkoxy, haloC1-4alkyloxy, —C1-4alkylC1-4alkoxy, C1-4alkoxyC1-4alkoxy, NR4AR4B, NO2, —CONR4AR4B, —C1-4alkylNR4AR4B, —C1-4alkoxyNR4AR4B, C3-7cycloalkyl, morpholinyl, C2-4alkynyl and —CO2R4 wherein
• R3 is hydrogen or C1-4alkyl,
• R4 is hydrogen or C1-4alkyl,
• R4A and R4B are each independently selected from hydrogen, C1-4alkyl, —C1-4alkylC1-4 alkoxy, and COR4, or
• R4A and R4B, together with the nitrogen atom to which they are attached, join together to form a cyclic amino group, wherein the cyclic amino group is optionally substituted with oxo;
• Ar2 is a ring system selected from Groups (i), and (ii), wherein:
• Group (i) is a 5-membered heteroaryl ring system selected from any one of (IIa) to (IIm):
• wherein X6, X7, X8, and X9 are each independently selected from O, S, and NH, and
• R5 is one or more optional substituents each independently selected from halogen, cyano, C1-4alkyl, haloC1-4alkyl, C1-4alkoxy, —C1-4alkylC1-4alkoxy, —CO2R6, and -L-Q wherein:
• L is a linker group selected from a direct bond, C1-3alkylene and —CO—;
• and
• Q is a group selected from NR5AR5B, C3cycloalkyl and 4-7 membered heterocyclyl, wherein the 4-7 membered heterocyclyl ring is optionally substituted with one or more substituents selected from halogen, cyano, C1-4alkyl, C1-4alkoxy and CO2R6;
• R5A and R5B are each independently selected from hydrogen, C1-4alkyl, C3-7cycloalkyl, COR7, —C1-4alkyl-NR8R9, —C1-4alkylC1-4alkoxy, phenyl and 5 or 6-membered heteroaryl wherein the phenyl or 5 or 6-membered heteroaryl rings are optionally substituted with one or more substituents selected from halogen and C1-4alkyl;
• or
• R5A and R5B, together with the nitrogen atom to which they are attached, join together to form a cyclic amino group, which cyclic amino group is optionally substituted with one or more groups selected from halogen, C1-4alkyl, C1-4alkoxy, cyano, and CO2R6,
• R6 is hydrogen, C1-4alkyl or an alkali metal;
• R7 is C1-4alkyl
• R8 and R9 are each independently selected from hydrogen and C1-4alkyl;
• Group (ii) is a 5,6-fused bicyclic heteroaryl ring system having the formula (III):
• wherein Y2 is selected from O and NR5C;
• R5C is hydrogen or C1-4alkyl,
• X10, X11, X12, and X13 are each independently selected from N and CH;
• R10 is one or more optional substituents each independently selected from halogen, cyano, C1-4alkyl, haloC1-4alkyl, C1-4alkoxy, and —CO2R4;
• PROVIDED THAT the compound of formula (I) is other than:

A compound of formula (I), or a pharmaceutically acceptable salt, hydrate, solvate, isomer, tautomer, N-oxide, ester, isotope or protected form thereof for use in the treatment of infection with, or disease caused by a bacterium selected from Moraxella catarrhalis, Acinetobacter junii, Helicobacter pylori, Borelia burgdorferi, Legionella pneumophilia, Neisseria gonorrhoeae, Neisseria meningitidis, Listeria monocytogenes, Streptococcus pyogenes (Group A Streptococcus), Streptococcus agalactiae (Group B Streptococcus), Streptococcus viridans, Streptococcus faecalis, Streptococcus bovis, any anaerobic species of the genus Streptococcus, Streptococcus pneumoniae, Campylobacter spp., Enterococcus spp., Haemophilus influenzae, Bacillus anthracis, Corynebacterium spp. (including C. diphtheriae), Erysipelothrix rhusiopathiae, Clostridium perfringens, Clostridium tetani, Clostridium difficile, Clostridium innocuum, Peptostreptococcus anaerobius, Bacteroides fragilis, Enterobacter aerogenes, Klebsiella spp (including K. pneumoniae), Pasteurella multocida, Bacteroides spp., Fusobacterium nucleatum, Streptobacillus monilijormis, Treponema pallidium, Treponema pertenue, Leptospira spp., Rickettsia spp. and Actinomyces spp. (including A. israelii), Acinetobater baumannii, and Pseudomonas aeruginosa:

• wherein R1 is selected from hydrogen and C1-4alkyl;
• Ar1 is selected from any one of the following ring systems:
• wherein R2 is one or more optional substituents each independently selected from halogen, cyano, hydroxyl, hydroxylC1-4alkyl, C1-4alkyl, haloC1-4alkyl, C1-4alkoxy, haloC1-4 alkyloxy, —C1-4alkylC1-4alkoxy, C1-4alkoxyC1-4alkoxy, NR4AR4B, NO2, —CONR4AR4B, —C1-4 alkylNR4AR4B, —C1-4alkoxyNR4AR4B, C3-7cycloalkyl, morpholinyl, C2-4alkynyl and —CO2R4 wherein
• R3 is hydrogen or C1-4alkyl,
• R4 is hydrogen or C1-4alkyl,
• R4A and R4B are each independently selected from hydrogen, C1-4alkyl, —C1-4alkylC1-4 alkoxy, and COR4, or
• R4A and R4B, together with the nitrogen atom to which they are attached, join together to form a cyclic amino group, wherein the cyclic amino group is optionally substituted with oxo;
• Ar2 is a ring system selected from Groups (i), and (ii), wherein:
• Group (i) is a 5-membered heteroaryl ring system selected from any one of (IIa) to (IIm):
• wherein X6, X7, X8, and X9 are each independently selected from O, S, and NH, and
• R5 is one or more optional substituents each independently selected from halogen, cyano, C1-4alkyl, haloC1-4alkyl, C1-4alkoxy, —C1-4alkylC1-4alkoxy, —CO2R6, and -L-Q wherein:
• L is a linker group selected from a direct bond, C1-3alkylene and —CO—;
• and
• Q is a group selected from NR5AR5B, C3cycloalkyl and 4-7 membered heterocyclyl, wherein the 4-7 membered heterocyclyl ring is optionally substituted with one or more substituents selected from halogen, cyano, C1-4alkyl, C1-4alkoxy and CO2R6;
• R5A and R5B are each independently selected from hydrogen, C1-4alkyl, C3-7cycloalkyl, COR7, —C1-4alkyl-NR8R9, —C1-4alkylC1-4alkoxy, phenyl and 5 or 6-membered heteroaryl wherein the phenyl or 5 or 6-membered heteroaryl rings are optionally substituted with one or more substituents selected from halogen and C1-4alkyl;
• or
• R5A and R5B, together with the nitrogen atom to which they are attached, join together to form a cyclic amino group, which cyclic amino group is optionally substituted with one or more groups selected from halogen, C1-4alkyl, C1-4alkoxy, cyano, and CO2R6,
• R6 is hydrogen, C1-4alkyl or an alkali metal;
• R7 is C1-4alkyl
• R8 and R9 are each independently selected from hydrogen and C1-4alkyl;
• Group (ii) is a 5,6-fused bicyclic heteroaryl ring system having the formula (III):
• wherein Y2 is selected from O and NR5C;
• R5C is hydrogen or C1-4alkyl,
• X10, X11, X12, and X13 are each independently selected from N and CH;
• R10 is one or more optional substituents each independently selected from halogen, cyano, C1-4alkyl, haloC1-4alkyl, C1-4alkoxy, and —CO2R4;
• PROVIDED THAT the compound of formula (I) is other than:
• and preferably wherein the compound of formula (I) is for use in the treatment of infection with, or disease caused by a bacterium selected from Enterococcus faecalis, Enterococcus faecium and the Neisseria genus;
• more preferably for use in the treatment of infection with, or disease caused by a bacterium selected from the Neisseria genus;
• and most preferably for use in the treatment of infection with, or disease caused by the bacterium Neisseria gonorrhoeae.