Antibacterial compounds

摘要

Disclosed are compounds of formula (I), which are of use in the treatment of bacterial diseases and infections, to compositions containing those compounds and to methods of treating bacterial diseases and infections using the compounds. In particular, the compounds are useful for the treatment of infection with, and diseases caused by, Clostridium difficile.;

主权项

1. A method of treating Clostridium difficile-associated disease (CDAD) in a subject in need thereof, the CDAD selected from the group consisting of diarrhoea caused by Clostridium difficile, bloating caused by Clostridium difficile, flu-like symptoms caused by Clostridium difficile, fever caused by Clostridium difficile, appetite loss caused by Clostridium difficile, abdominal pain caused by Clostridium difficile, nausea caused by Clostridium difficile, dehydration caused by Clostridium difficile, colitis caused by Clostridium difficile and pseudomembraneous colitis caused by Clostridium difficile, which method comprises
a) detecting infection and/or intoxication of the subject with one or more strains of Clostridium difficile; b) administering to the subject an effective amount of a compound of formula (I):wherein:
L1 is a direct bond or a linker group; R1 and R2 are each independently selected from H and optionally substituted C1-6 alkyl, aryl, heteroaryl, carbocyclyl and heterocyclyl, the optional substitution being with one or more substituents selected from halo, CN, NO2, R6, OR6, N(R6)2, COR6, CO2R6, SO2R6, NR7COR6, NR7CO2R6, NR7SO2R6, NR7CONR6R7, CONR6R7 and SO2NR6R7, provided that at least one of R1 and R2 is cyclic; each R5 is independently selected from H, halo, C1-6 alkyl, OR7, N(R7)2, CN and NO2; X1 and X2 are each independently selected from N and CR3; X3 is selected from NR4, O and S; X4 is NH; and R3 is selected from H, halo and C1-6 alkyl; R4 is selected from H and C1-6 alkyl; R6 is selected from H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C4-C7 carbocyclyl, C4-C7 heterocyclyl and 5- or 6-membered aryl or heteroaryl, any of which may be optionally substituted with one or more halo atoms; and R7 is selected from hydrogen and C1-C4 alkyl, each of which C1-C4 alkyl is optionally substituted with one or more halo atoms;or a pharmaceutically acceptable N-oxide, salt, hydrate, solvate; and
c) preventing or reducing the rate of bacterial growth, and/or mediating the cellular destruction of bacterial cells, of the one or more strains of Clostridium difficile.