Heterocyclic compounds, in particular 2-oxo-4,4,5,5,6,6,7,7-octahydrobenzoxazole derivatives, and their use as antibacterial compounds

A method of treating a bacterial infection or a mycobacterial infection comprising administering to a patient in need thereof a therapeutic amount of a compound of formula (I), or a pharmaceutically acceptable salt or N-oxide thereof:

• wherein is a double bond or a single bond;
• Y1 is independently selected from the group consisting of NR4, O and S;
• Y2 is independently selected from the group consisting of O and S;
• Y3 is independently selected from the group consisting of O and S;
• Y4 is (CH2)m;
• Y5 is (CH2)p;
• R1 is independently selected from the group consisting of -L1-Ar1—Ar2 and
• Ar1 and Ar2 are each independently a phenyl or monocyclic heteroaryl group;
• -L1- is —C1-C3-alkylene-;
• X1 is independently selected from the group consisting of N and CR5;
• and X2 is independently selected from the group consisting of N and CR6;
• or
• X1 and X2 together form a 5-membered heteroaryl ring;
• -L2- is —C2-C3-alkylene-;
• Ring B is independently selected from the group consisting of phenyl, monocyclic 6-membered heteroaryl and pyridinone, optionally substituted with a single —Y6—R7 group;
• wherein Y6 is absent or is independently selected from the group consisting of NR8, O and S;
• where Ring B is a pyridinone ring, the nitrogen of the Ring B pyridinone may be attached to the proximal end of a —C1-C3-alkylene- group that is attached at its distal end to the group -L2-;
• R2 is independently at each occurrence selected from the group consisting of halo, nitro, cyano, NR9R10, NR9S(O)2R9, NR9CONR9R9, NR9C(O)R9, NR9CO2R9, OR9, SR9, SOR9, SO3R9, SO2R9, SO2NR9R9, CO2R9, C(O)R9, CONR9R9, C1-C4-alkyl, C2-C4-alkenyl, C2-C4-alkynyl, C1-C4-haloalkyl and O—C1-C4-haloalkyl;
• R3 is a bicyclic carbocyclic or a bicyclic heterocyclic ring system in which at least one of the two rings is aryl or heteroaryl;
• or R3 is -L3-phenyl;
• wherein -L3- is selected from the group consisting of —CR11═CR11— and —C4-cycloalkyl-;
• R4 is independently selected from the group consisting of H, C1-C4-alkyl, C(O)—C1-C4-alkyl and C1-C3-alkylene-R12;
• wherein R12 is independently phenyl or monocyclic heteroaryl;
• or wherein R4 and either -L1- or -L2- and the nitrogen to which they are attached together form a 4- to 7-membered heterocycloalkyl ring;
• R5 and R6 are each independently selected from the group consisting of H, halo, cyano, C1-C4-alkyl and O—C1-C4-alkyl;
• R7 is independently selected from the group consisting of H, C1-C4-alkyl, C2-C4-alkenyl, C2-C4-alkynyl, C1-C4-haloalkyl, C3-C8-cycloalkyl, 4-7-heterocycloalkyl, phenyl, monocyclic heteroaryl and C1-C3-alkylene-R7a;
• wherein R7a is independently selected from the group consisting of C3-C8-cycloalkyl, 4-7-heterocycloalkyl, phenyl and monocyclic heteroaryl;
• R8 is independently selected from the group consisting of H and C1-C4-alkyl;
• or R7 and R8 together with the nitrogen to which they are attached form a 4- to 7-membered heterocycloalkyl ring;
• R9 is independently at each occurrence selected from the group consisting of H and C1-C4-alkyl;
• R10 is independently selected from the group consisting of H, C1-C4-alkyl, C1-C4-haloalkyl, S(O)2—C1-C4-alkyl and C(O)—C1-C4-alkyl;
• R11 is independently at each occurrence selected from the group consisting of H and C1-C4-alkyl;
• a is an integer from 0 to 4;
• n is an integer selected from the group consisting of 0, 1 and 2;
• m and p are each an integer selected from the group consisting of 0 and 1;
• wherein any of the aforementioned alkyl, alkylene, alkenyl, alkynyl, haloalkyl, cycloalkyl, carbocyclic, heterocyclic, heterocycloalkyl, aryl, phenyl and heteroaryl groups is optionally substituted, where chemically possible, by 1 to 5 substituents which are each independently at each occurrence selected from the group consisting of oxo, ═NRa, ═NORa, halo, nitro, cyano, NRaRa, NRaS(O)2Ra, NRaC(O)Ra, NRaCONRaRa, NRaCO2Ra, ORa, SRa, SORa, SO3Ra, SO2Ra, SO2NRaRa, CO2Ra, C(O)Ra, CONRaRa, CRaRaNRaRa, CRaRaORa, C1-C4-alkyl, C2-C4-alkenyl, C2-C4-alkynyl, C1-C4-haloalkyl and O—C1-C4-haloalkyl;
• wherein Ra is independently at each occurrence selected from the group consisting of H, C1-C4-alkyl.