Indoles Useful in the Treatment of Inflammation

A compound of formula I,

• wherein
• X represents a single bond, —C(O)— or —S(O)2—;
• R1 represents an aryl group or a heteroaryl group, both of which groups are optionally substituted by one or more substituents selected from A;
• one of the groups R2, R3, R4 and R5 represents an aryl group or a heteroaryl group (both of which are optionally substituted by one or more substituents selected from A) and:
• a) the other groups are independently selected from hydrogen, G1, an aryl group, a heteroaryl group (which latter two groups are optionally substituted by one or more substituents selected from A), C1-8 alkyl and a heterocycloalkyl group (which latter two groups are optionally substituted by one or more substituents selected from G1 and/or Z1);
• and/or
• b) any two other groups which are adjacent to each other are optionally linked to form, along with two atoms of the essential benzene ring in the compound of formula I, a 3- to 8-membered ring, optionally containing 1 to 3 heteroatoms and/or 4 1 to 3 double bonds, which ring is itself optionally substituted by one or more substituents selected from halo, —R8, —OR8 and ═O;
• R6, R7 and R8 independently represent, on each occasion when used above:
• I) hydrogen;
• II) an aryl group or a heteroaryl group, both of which are optionally substituted by one or more substituents selected from B;
• III) C1-8 alkyl or a heterocycloalkyl group, both of which are optionally substituted by one or more substituents selected from G1 and/or Z1;
• or
• R6 and R7 may be linked together to form along with the N atom and X group to which R6 and R7 are respectively attached, a 3- to 8-membered ring, optionally containing 1 to 3 heteroatoms and/or 1 to 3 double bonds, which ring is optionally substituted by one or more substituents selected from G1 and/or Z1;
• A represents, on each occasion when mentioned above:
• I) an aryl group or a heteroaryl group, both of which are optionally substituted by one or more substituents selected from B;
• II) C1-8 alkyl or a heterocycloalkyl group, both of which are optionally 20 substituted by one or more substituents selected from G1 and/or Z1;
• III) a G1 group;
• or
• IV) two A substituents may be linked together to form, along with at least two (e.g. adjacent) atoms of the aryl or heteroaryl group to which the two A substituents are attached, a further 3- to 5-membered ring, which ring optionally contains 1 to 3 hetereoatoms and/or 1 to 2 double bonds, and which is optionally substituted by halo or C1-8 alkyl, which latter group is optionally substituted by halo;
• G1 represents, on each occasion when mentioned above, halo, cyano, —N3, —NO2, —ONO2 or -A1-R9;
• wherein A1 represents a single bond or a spacer group selected from —C(O)A2-, —S(O)nA3-, —N(R10)A4- or —OA5-, in which:
• A2 and A3 independently represent a single bond, —O—, —N(R10)— or —C(O)—;
• A4 and A5 independently represent a single bond, —C(O)—, —C(O)N(R10)—, —C(O)O—, —S(O)n— or —S(O)nN(R10)—;
• Z1 represents, on each occasion when mentioned above, ═O, ═S, ═NOR9, ═NS(O)nN(R10)(R9), ═NCN or ═C(H)NO2;
• B represents, on each occasion when mentioned above:
• I) an aryl group or a heteroaryl group, both of which are optionally substituted by one or more substituents selected from G2, methylenedioxy, difluoromethylenedioxy and/or dimethylmethylenedioxy;
• II) C1-8 alkyl or a heterocycloalkyl group, both of which are optionally substituted by one or more substituents selected from G2 and/or Z2;
• III) a G2 group;
• or
• IV) methylenedioxy, difluoromethylenedioxy or dimethylmethylenedioxy;
• G2 represents, on each occasion when mentioned above, halo, cyano, —N3, —NO2, —ONO2 or -A6-R11;
• wherein A6 represents a single bond or a spacer group selected from —C(O)A7-, —S(O)nA8-, —N(R12)A9- or —OA10-, in which:
• A7 and A8 independently represent a single bond, —O—, —N(R12)— or —C(O)—;
• A9 and A10 independently represent a single bond, —C(O)—, —C(O)N(R12)—, —C(O)O—, —S(O)n— or —S(O)nN(R12)—;
• Z2 represents, on each occasion used above ═O, ═S, ═NOR11, when ═NS(O)nN(R12)(R11), ═NCN or —C(H)NO2;
• R9, R10, R11 and R12 are independently selected from:
• i) hydrogen;
• ii) an aryl group or a heteroaryl group, both of which are optionally substituted by one or more substituents selected from G3, methylenedioxy, difluoromethylenedioxy and/or dimethylmethylenedioxy;
• iii) C1-8 alkyl or a heterocycloalkyl group, both of which are optionally substituted by G3 and/or Z3;
• or
• any pair of R9 and R10, or R11 and R12, may, for example when present on the same or on adjacent atoms, be linked together to form with those, or other relevant, atoms a further 3- to 8-membered ring, optionally containing 1 to 3 heteroatoms and/or 1 to 3 double bonds, which ring is optionally substituted by one or more substituents selected from G3 and/or Z3;
• G3 represents, on each occasion when mentioned above, halo, cyano, —N3, —NO2, —ONO2 or -A11-R13;
• wherein A11 represents a single bond or a spacer group selected from —C(O)A12-, —S(O)nA13-, —N(R14)A14- or —OA15-, in which:
• A12 and A13 independently represent a single bond, —O—, —N(R14)— or —C(O)—;
• A14 and A15 independently represent a single bond, —C(O) . . . ;
• —C(O)N(R14)—, —C(O)O—, —S(O)n— or —S(O)nN(R14)—;
• Z3 represents, on each occasion when mentioned above, ═O, ═S, ═NOR13, ═NS(O)nN(R14)(R13), ═NCN or ═C(H)N02;
• n represents, on each occasion when mentioned above, 1 or 2;
• R13 and R14 are independently selected from:
• i) hydrogen;
• ii) C1-6 alkyl or a heterocycloalkyl group, both of which groups are optionally substituted by one or more substituents selected from halo, C1-4 alkyl, —N(R15)(R16), —O(R15) and ═O;
• and
• iii) an aryl or heteroaryl group, both of which are optionally substituted by one or more substituents selected from halo, C1-4 alkyl, —N(R15)(R16) and —O(R15);
• or
• any pair R13 and R14 may, for example when present on the same or on adjacent atoms, be linked together to form with those, or other relevant, atoms a further 3- to 8-membered ring, optionally containing 1 to 3 heteroatoms and/or 1 to 3 double bonds, which ring is optionally substituted by one or more substituents selected from halo, C1-4 alkyl, —N(R15)(R16), —O(R15) and ═O;
• R15 and R16 are independently selected from hydrogen and C1-4 alkyl, which latter group is optionally substituted by one or more halo groups;
• or a pharmaceutically-acceptable salt thereof.