Compounds for the treatment of <i>Clostridium difficile </i>associated disease

摘要

Disclosed are compounds of formula (I):;
and pharmaceutically acceptable N-oxides, salts, hydrates, solvates, complexes, bioisosteres, metabolites, and prodrugs thereof, which are of use in the treatment of infection with, and diseases caused by, Clostridium difficile.

主权项

1. A method of treating a Clostridium difficile infection or Clostridium difficile-associated disease in a subject comprising administering to the subject an effective amount of a compound of formula (I):or a pharmaceutically acceptable N-oxide, salt, hydrate, solvate, complex, bioisostere, or metabolite thereof;wherein:
R1 is selected from the group consisting of optionally substituted aryl, optionally substituted heteroaryl, optionally substituted carbocyclyl, and optionally substituted heterocyclyl, the optional substitution being with one or more substituents selected from the group consisting of halo, CN, NO2, R3, OR3, N(R3)2, COR3, CO2R3, C(═O)SR3, SR3, S(═O)R3, SO2R3, NR4C(═O)R3, NR4CO2R3, OC(═O)NR3R4, NR4SO2R3, C(═NR4)NR3R4, C(═S)NR3R4, NR4C(═NR4)NR3R4, NR4C(═S)NR3R4, NR4C(═O)NR3R4, CONR3R4 and SO2NR3R4; R2 is an optionally substituted aromatic 8-14 membered fused bicyclic ring system or an optionally substituted aromatic 8-14 membered fused tricyclic ring system, wherein one or more of the carbon atoms of the ring system may be replaced by N, O, S, SO or SO2 and the optional substitution being with one or more substituents selected from the group consisting of halo, CN, NO2, R3, OR3, N(R3)2, COR3, CO2R3, C(═O)SR3, SR3, S(═O)R3, SO2R3, NR4C(═O)R3, NR4CO2R3, OC(═O)NR3R4, NR4SO2R3, C(═NR4)NR3R4, C(═S)NR3R4, NR4C(═NR4)NR3R4, NR4C(═S)NR3R4, NR4C(═O)NR3R4, CONR3R4 and SO2NR3R4; R3 is selected from the group consisting of hydrogen, optionally substituted C1-C6 alkyl, optionally substituted C2-C6 alkenyl, optionally substituted C2-C6 alkynyl, optionally substituted C3-C7 carbocyclyl, optionally substituted C4-C7 heterocyclyl, optionally substituted 6-membered aryl, or optionally substituted 5- or 6-membered heteroaryl, the optional substitution being with one or more substituents selected from the group consisting of halo, CN, NO2, R4, OR4, N(R4)2, COR4, CO2R4, C(═O)SR4, SR4, S(═O)R4, SO2R4, NR4C(═O)R4, NR4CO2R4, OC(═O)NR4)2, NR4SO2R4, C(═NR4)N(R4)2, C(═S)N(R4)2, NR4C(═NR4)N(R4)2, NR4C(═S)N(R4)2, NR4C(═O)N(R4)2, CON(R4)2 and SO2N(R4)2; and R4 is selected from the group consisting of hydrogen, optionally substituted C1-C6 alkyl, and optionally substituted C3-C7 carbocyclyl, the optional substitution being with one or more halo atoms.