Piperidinones Useful in the Treatment of Inflammation

A compound of formula (I),

• wherein:
• m and q each independently represent 0, 1, 2, 3, 4 or 5;
• n represents 0, 1, 2 or 3;
• r represents 1, 2, 3, 4, 5 or 6;
• R1 represents C1-12 alkyl, C2-12 alkenyl, C2-12 alkynyl, halo, -A1-B1, —R12—CN, —R12—NO2, —R12—N(R10)R11, —R12—OR10, —R12—OC(O)R10, —R12—C(O)R13, —R12—C(O)OR10, —R12—C(O)N(R10)R11, —R12—N(R10)C(O)N(R10)R11, —R12—O—R9—C(O)OR10, —R12—O—R9—C(O)N(R10)R11, —R12—S(O)pxR10, —R12—OS(O)2R10, —R12—S(O)txN(R10)R11, —R12—N(R10)S(O)txN(R10)R11, —R12—C(═NR10)N(R10)R11, —R12—C(═NOH)N(R10)R11, —R12—B(OR10)2, —R12—P(R10)R11, —R12—P(O)(OR10)2 or —R12—OP(O)(OR10)2, wherein C1-12 alkyl, C2-12 alkenyl, C2-12 alkynyl are optionally substituted by one or more substituents selected from X1;
• tx represents 1 or 2;
• px represents 0, 1, 2 or 3;
• R2 represents hydrogen, —OR4, C1-12 alkyl, C2-12 alkenyl, C2-12 alkynyl or -A2-B2, wherein C1-12 alkyl, C2-12 alkenyl, C2-12 alkynyl are optionally substituted by one or more substituents selected from X2;
• R3 represents hydrogen, —OR4, —R12—O—R9—C(O)OR10, —R12—O—R9—C(O)N(R10)R11, C1-12 alkyl, C2-12 alkenyl, C2-12 alkynyl or -A3-B3, wherein C1-12 alkyl, C2-12 alkenyl, C2-12 alkynyl are optionally substituted by one or more substituents selected from X2;
• provided that when r represents 1 and q is other than 0, then either:
• R1 represents -A1-B1, —R12—CN, —R12—NO2, —R12—N(R10)R11, —R12—OC(O)R10, —R12—C(O)R13, —R12—C(O)OR10, —R12—C(O)N(R10)R11, —R12—N(R10)C(O)N(R10)R11, —R12—O—R9—C(O)OR10, —R12—O—R9—C(O)N(R10)R11, —R12—S(O)pxR10, —R12—OS(O)2R10, —R12—S(O)txN(R10)R11, —R12—N(R10)S(O)txN(R10)R11, —R12—C(═NR10)N(R10)R11, —R12—C(═NOH)N(R10)R11, —R12—B(OR10)2, —R12—P(R10)R11, —R12—P(O)(OR10)2 or —R12—OP(O)(OR10)2;
• or
• R3 represents —R12—O—R9—C(O)OR10 or —R12—O—R9—C(O)N(R10)R11;
• R4 represents hydrogen, —R9—OR10, —R9—C(O)OR10, C1-12 alkyl, C2-12 alkenyl, C2-12 alkynyl (which latter three groups are optionally substituted by one or more substituents selected from X3) or -A4-B4;
• R5 represents hydrogen, -A5-B5, —R12—C(O)R10, —R12—C(O)OR10, —R12—C(O)N(R10)R11, C1-12 alkyl, C2-12 alkenyl or C2-12 alkynyl, which latter three groups are optionally substituted by one or more substituents selected from X4;
• each R6 independently represents halo, —R12—OR10, —R12—CN, —R12—NO2, —R12—C(O)OR10, —R12—N(R10)R11, —R12—C(O)N(R10)R11, —R12—N(Rw3)C(O)R10, —R12—N(Rw3)C(O)N(R10)R11, —R12—N(Rw3)S(O)tR10x, —R12—N(Rw3)S(O)tOR10x, —R12—OC(O)R10, —R12—OC(O)N(R10)R11, —R12—OS(O)tR10x, —R12—S(O)pR10, —R12—S(O)tN(Rw3)R10, —R12—S(O)tOR10;
• —R12—Si(R16)3, C1-12 alkyl, C1-12 alkenyl, C1-12 alkynyl, C3-15 cycloalkyl and/or heterocyclyl which latter five groups are optionally substituted by one or more substituents selected from X5;
• or
• any two R6 groups, or R2 and any R6 group, may be linked together to form a further ring, which is formed either by the two relevant groups being linked together by a direct bond or C1-5 alkylene;
• R7 represents halo, —R12—OR10, —R12—CN, —R12—NO2, —R12—C(O)OR10, —R12—N(R10)R11, —R12—C(O)N(R10)R11, —R12—N(Rw3)C(O)R10, —R12—N(Rw3)C(O)N(R10)R11, —R12—N(Rw3)S(O)tR10x, —R12—N(Rw3)S(O)tOR10x, —R12—OC(O)R10, —R12—OC(O)N(R10)R11, —R12—OS(O)tR10x, —R12—S(O)pR10, —R12—S(O)tN(Rw3)R10, —R12—S(O)tOR10;
• —R12—Si(R16)3, C1-12 alkyl, C1-12 alkenyl, C1-12 alkynyl, C3-15 cycloalkyl or heterocyclyl which latter five groups are optionally substituted by one or more substituents selected from X6;
• R8 represents hydrogen, —R12—O—R10, -A6-B6, C1-12 alkyl, C2-12 alkenyl or C2-12 alkynyl, which latter three groups are optionally substituted by one or more substituents selected from X7;
• R10x represents C1-12 alkyl, C2-12 alkenyl, C2-12 alkynyl, -A7-O-A8 or -A9-B9, wherein C1-12 alkyl, C2-12 alkenyl, C2-12 alkynyl are optionally substituted by one or more substituents selected from X8;
• Rw3, R10 and R11 each independently represent hydrogen, C1-12 alkyl, C2-12 alkenyl, C2-12 alkynyl, -A7-O-A8 and/or -A9-B9, wherein C1-12 alkyl, C2-12 alkenyl, C2-12 alkynyl are optionally substituted by one or more substituents selected from X8;
• or R10 and R11, together with the nitrogen atom to which they are both attached, may be linked together to form a heterocyclyl group optionally substituted by one or more substituents selected from Z2a or a heteroaryl group optionally substituted by one or more substituents selected from Z1a;
• or
• in the case of —R12—B(OR10)2, the two R10 groups may be linked together to form, along with the relevant boron and oxygen atoms, a heterocyclyl group;
• R12 represents a direct bond or R9;
• R13 represents hydrogen, halo, C1-12 alkyl, C2-12 alkenyl, C2-12 alkynyl (which latter three groups are optionally substituted by one or more substituents selected from X9), -A10-O-A11 or -A12-B12;
• R9 represents C1-12 alkylene, C2-12 alkenylene or C2-12 alkynylene, all of which are optionally substituted by one or more substituents selected from X10;
• A1, A3, A4, A9 and A12 each independently represent a direct bond, C1-12 alkylene, C2-12 alkenylene or C2-12 alkynylene, which latter three groups are optionally substituted by one or more substituents selected from X11;
• A2, A5, A6, A7 and A10 each independently represent C1-12 alkylene, C2-12 alkenylene or C2-12 alkynylene, all of which are optionally substituted by one or more substituents selected from X12;
• A8 and A11 each independently represent C1-12 alkyl, C2-12 alkenyl or C2-12 alkynyl, all of which are optionally substituted by one or more substituents selected from X13;
• B1, B3, B4, B9 and B12 each independently represent aryl optionally substituted by one or more substituents selected from Y1, heteroaryl optionally substituted by one or more substituents selected from Z1, heterocyclyl optionally substituted by one or more substituents selected from Z2 or cycloalkyl optionally substituted by one or more substituents selected from Z3;
• B2, B5 and B6 each independently represent aryl optionally substituted by one or more substituents selected from Y2;
• X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12 and X13 each independently represent G1, aryl optionally substituted by one or more T1 substituents, C3-15 cycloalkyl optionally substituted by one or more T2 substituents, heterocyclyl optionally substituted by one or more T3 substituents, heteroaryl optionally substituted by one or more T4 substituents, ═O, —Si(R16)3, —OR14, —OC(O)—R14, —N(R14)2, —C(O)R14, —C(O)OR14, —C(O)N(R14)2, —N(R14)C(O)OR16, —N(R14)C(O)R16, —N(R14)S(O)tR16, —S(O)tOR16, —S(O)pR16, —S(O)tN(R14)2, —N(R14)C(O)N(R14)2, —N(R14)S(O)tOR16, —OC(O)N(R14)2 or —OS(O)tR9x;
• Y1 and Y2 each independently represent -Ax-By, G1, G2, —R15—OR17—N(R14)2 or —R15—O—R17—N(R14)S(O)tR16;
• Z1a, Z1, Z2a, Z2 and Z3 each independently represent G1, ═O, ═S, -Ax-By or G2;
• G1 represents C1-12 alkyl optionally substituted by one or more substituents selected from T5 or C2-12 alkenyl optionally substituted by one or more substituents selected from T6, halo, —CN, —NO2 or ═O;
• G2 represents -Ax-Bx, —R15—OR14, —R15—OC(O)—R14, —R15—N(R14)2, —R15—C(O)R14, —R15—C(O)OR14, —R15—C(O)N(R14)2, —R15—N(R14)C(O)OR16, —R15—N(R14)C(O)R16, —R15—N(R14)S(O)tR16, —R15—S(O)tOR16, —R15—S(O)pR16 or —R15—S(O)tN(R14)2;
• Ax represents a direct bond or C1-12 alkylene optionally substituted by one or more halo or ═O substituents;
• Bx represents aryl or heteroaryl, which groups are optionally substituted by one or more substituents selected from T7 and T8, respectively;
• By represents cycloalkyl or heterocyclyl, both of which are optionally substituted by one or more substituents selected from halo, C1-6 alkyl, —OCH3, —OCHF2, —OCF3 and/or ═O, wherein C1-12 alkyl, is optionally substituted by one or more halo substituents;
• T1, T4, T5, T6, T7 and T8 each independently represent halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl which latter three groups are optionally substituted by one or more substituents selected from Qx1, —OH, —O—C1-6 alkyl, —OC2-6 alkenyl, —OC2-6 alkynyl which latter three groups are optionally substituted by one or more substituents selected from Qx2, —N(Rw)2, —NO2 and/or —CN;
• or
• T5 and T6 may alternatively or additionally represent ═O;
• T2 and T3 each independently represent halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, —OCH3, —OCHF2, —OCF3 and/or ═O, wherein C1-12 alkyl, C2-12 alkenyl, C2-12 alkynyl are optionally substituted by halo;
• Qx1 and Qx2 each independently represent halo, —OCH3, —OCHF2, —OCF3, —N(Rw)2 or ═O;
• Rw represents hydrogen, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, which latter three groups are optionally substituted by one or more substituents selected from halo, —OCH3, —OCHF2, —OCF3 or ═O;
• or
• two Rw groups, when attached to the same nitrogen atom, may be linked together to form, together with the nitrogen atom to which they are necessarily attached, a 5- or 6-membered ring, optionally containing a further heteroatom and optionally substituted by one or more substituents selected from fluoro, —CH3 or ═O;
• t represents 1 to 2;
• p represents 0, 1 or 2;
• R14 represents hydrogen, -Ax1-Bx1, C1-12 alkyl, C2-6 alkenyl or C2-6 alkynyl, which latter three groups are optionally substituted by one or more substituents selected from E1;
• R15 represents a direct bond, C1-12 alkylene or C2-12 alkenylene, which latter two groups are optionally substituted by one or more substituents selected from halo, —OCH3, —OCHF2, —OCF3 or ═O;
• R16 represents C1-12 alkyl, C2-6 alkenyl, C2-6 alkynyl or -Ay1-By1, wherein C1-12 alkyl, C2-12 alkenyl, C2-12 alkynyl are optionally substituted by one or more halo and/or ═O groups;
• R17 represents C1-12 alkylene or C2-12 alkenylene, both of which are optionally substituted by one or more substituents selected from halo and ═O;
• Ax1 and Ay1 each independently represent a direct bond or C1-12 alkylene optionally substituted by one or more halo or ═O groups;
• Bx1 and By1 each independently represent cycloalkyl optionally substituted by one or more substituents selected from halo and ═O, heterocyclyl optionally substituted by one or more substituents selected from halo and ═O, aryl optionally substituted by one or more halo atoms or heteroaryl optionally substituted by one or more halo atoms;
• E1 represents halo, —CN, —NO2, ═O, —OR18, —OC(O)—R18, —N(R18)2, —C(O)R18, —C(O)OR18, —C(O)N(R18)2, —N(R18)C(O)OR19, —N(R18)C(O)R19, —N(R18)S(O)t1R19, —S(O)t1OR19, —S(O)p1R19, —S(O)t1N(R18)2, —N(R18)C(O)N(R18)2, —N(R18)S(O)t1OR19x, —OC(O)N(R18)2, —OS(O)t1R19x or —Si(R19x)3;
• R18 and R19 each independently represents hydrogen, C1-3 alkyl, C2-3 alkenyl or C2-3 alkynyl, which latter three groups are optionally substituted by one or more halo atoms;
• R19x represents C1-3 alkyl, C2-3 alkenyl or C2-3 alkynyl, which latter three groups are optionally substituted by one or more halo atoms;
• t1 represents 1 or 2;
• p1 represents 0, 1 or 2,
• or a pharmaceutically acceptable salt, solvate, prodrug or polymorph thereof.