Ror-gamma modulators and uses thereof

A compound of formula I,

• wherein:
• R1 is —S(O)mRa, —S(O)rNRbRc, —S(O)r(NRb)Ra, —NRaRb, —NRbCORc, —NRbS(O)mRa, —O—Rd or
• Ra is (C1-C8)-alkyl, (C3-C12)-cycloalkyl, (C6-C10)-aryl or heterocyclyl;
• Rb and Rc at each occurrence are independently selected from the group consisting of hydrogen, (C1-C8)-alkyl, (C3-C12)-cycloalkyl, (C6-C10)-aryl and heterocyclyl;
• or
• Rb and Rc can combine to form a saturated or unsaturated 5- or 6-membered ring, optionally containing 1 or 2 additional heteroatoms selected from the group consisting of N, S and O;
• wherein the ring can be unsubstituted or substituted with one or more groups independently selected from the group consisting of halogen, hydroxy, cyano, oxo, (C1-C8)-alkyl, (C1-C8)-alkoxy and halo(C1-C8)-alkyl;
• Rd is (C1-C8)-alkyl-O—(C1-C8)-alkyl or halo(C1-C8)-alkyl;
• Re is hydrogen, (C1-C8)-alkyl, (C1-C8)-alkoxy, halo(C1-C8)-alkyl, (C2-C8)-alkenyl or NRa1Ra2;
• X is O, NH, S(O)2 or S;
• m is 0, 1 or 2;
• n is O or 1;
• r is 1 or 2;
• R2 at each occurrence is independently selected from the group consisting of hydrogen, halogen, hydroxy, cyano, (C1-C8)-alkyl, (C1-C8)-alkoxy, (C3-C12)-cycloalkyl, halo(C1-C8)-alkyl, halo(C1-C8)-alkoxy, NRa1Ra2, CORa3, COORa3 and CONRa1Ra2;
• or
• R1 and R2 when present on adjacent carbon atoms of the phenyl can combine to form a saturated 5- or 6-membered ring containing S or SO2;
• which ring can be unsubstituted or substituted with one or more groups independently selected from the group consisting of halogen, cyano, oxo, (C1-C8)-alkyl, (C2-C8)-alkenyl, (C2-C8)-alkynyl, (C1-C8)-alkoxy and halo(C1-C8)-alkyl;
• R3 and R4 are independently selected from the group consisting of hydrogen, halogen, hydroxy, cyano, (C1-C8)-alkyl, (C2-C8)-alkenyl, (C1-C8)-alkoxy and halo(C1-C8)alkyl;
• a is 1 or 2;
• b is 1 or 2;
• L is —CO— or —SO2—;
• A is
• R5 is hydrogen, (C1-C8)-alkyl, halo(C1-C8)alkyl or (C3-C12)-cycloalkyl;
• R6 and R7 are independently selected from the group consisting of hydrogen, halogen, hydroxy, cyano, (C1-C8)-alkyl, (C2-C8)-alkenyl, (C1-C8)-alkoxy, halo(C1-C8)alkyl, (C3-C12)-cycloalkyl, (C6-C10)-aryl, CONRa1Ra2, CORa3 and COORa3;
• or
• R6 and R7 can combine to form saturated or unsaturated 3-6 membered cyclic ring optionally containing 1 or 2 heteroatoms selected from the group consisting of O, N and S;
• wherein the ring can be unsubstituted or substituted with one or more groups independently selected from the group consisting of oxo, hydroxy, cyano, halogen, (C1-C8)-alkyl, halo(C1-C8)-alkyl, CORa3, COORa3, CONRa2Ra3, (C1-C8)-alkoxy and halo(C1-C8)-alkoxy;
• R8 is hydrogen, halogen, hydroxy, cyano, (C1-C8)-alkyl, (C2-C8)-alkenyl, (C1-C8)-alkoxy, halo(C1-C8)alkyl, CONRa1Ra2, CORa3 or COORa3;
• T is CRt or N;
• Rt is hydrogen, cyano, halogen, (C1-C8)-alkyl, (C1-C8)-alkoxy, (C3-C12)-cycloalkyl, halo(C1-C8)-alkyl or halo(C1-C8)-alkoxy;
• c is 0, 1, 2 or 3;
• d is 1 or 2;
• Q is selected from the group consisting of,
• R9 is (CRfRj)fRb, (CRfRj)fORk, (CRfRj)fN(Rk)2, (CRfRj)fCN, (CRfRj)f-halogen, W—(C3-C12)-cycloalkyl, W—(C5-C10)-cycloalkenyl, W1—(C6-C10)-aryl, W1-heterocyclyl or W1-heteroaryl;
• R10 at each occurrence is independently selected from the group consisting of (CRfRj)fORk, oxo, W—(C3-C12)-cycloalkyl, (C6-C10)-aryl, W1—(C6-C10)-aryl and W1-heteroaryl;
• Rk is hydrogen, (C1-C8)-alkyl, (C3-C12)-cycloalkyl, (C5-C10)-cycloalkenyl, —(C1-C8)-alkylene-(C3-C12)-cycloalkyl, —(C1-C8)-alkylene-(C5-C10)-cycloalkenyl, (C6-C10)-aryl, —(C1-C8)-alkylene-(C6-C10)-aryl, heteroaryl, heterocyclyl, —(C1-C8)-alkylene-heteroaryl or —(C1-C8)-alkylene-heterocyclyl;
• Rx and Ry at each occurrence are independently selected from the group consisting of hydrogen, halogen, hydroxy, cyano, oxo, (C1-C8)-alkyl, (C1-C8)-alkoxy, (C3-C12)-cycloalkyl, halo(C1-C8)-alkyl, halo(C1-C8)-alkoxy, NRa1Ra2, CORa3, COORa3 and CONRa1Ra2;
• W is a bond, —O—, CO, NH, (CRfRg)f, (CRfRg)f—C≡C— or (C5-C10)-cycloalkenyl;
• W1 is (CRfRj)f, (CRfRg)f—C≡C— or (C5-C10)-cycloalkenyl;
• Rj is (C1-C8)alkyl, (C1-C8)alkoxy, halo(C1-C8)alkyl, COORa3 or heterocyclyl;
• Rf and Rg are independently selected from the group consisting of hydrogen, halogen, cyano, hydroxy, (C1-C8)alkyl and halo(C1-C8)alkyl;
• e is 1 or 2;
• f is 1, 2, 3 or 4;
• o is 0, 1, 2 or 3;
• R11 is hydrogen, (C1-C8)-alkyl, (C3-C12)-cycloalkyl, (C5-C10)-cycloalkenyl, (C6-C10)-aryl, (CRfRg)f—(C6-C10)-aryl, (CRfRg)f-heterocyclyl, COORa3 or CORa3;
• X1 is CR12R13, O, S or S(O)2;
• X2 is CR14R15 or C═R16;
• X3 is O or S;
• X4 is CR17 or N;
• X5 is CR18R19 or S;
• t is 0, 1 or 2;
• s is 1 or 2;
• R12, R13, R14, R15, R17, R18 and R19 are independently selected from the group consisting of hydrogen, halogen, hydroxy, cyano, (C1-C8)-alkyl, (C2-C8)-alkenyl, (C2-C8)-alkynyl, (C1-C8)-alkoxy, (C3-C12)-cycloalkyl, (C5-C10)-cycloalkenyl, halo(C1-C8)-alkyl, (C6-C10)-aryl, heteroaryl, heterocyclyl, NRa1Ra2, CORa3, COORa3, CONRa1Ra2, S(O)q(C1-C8)-alkyl and S(O)rNRa1Ra2;
• R16 is O, (C3-C12)-cycloalkyl, (C5-C10)-cycloalkenyl or heterocyclyl;
• Ra1, Ra2 and Ra3 at each occurrence are independently selected from the group consisting of hydrogen, (C1-C8)-alkyl and (C3-C12)-cycloalkyl;
• q is 0, 1 or 2;
• wherein:
• each of the (C1-C8)-alkyl, (C1-C8)-alkylene, (C2-C8)-alkenyl and (C1-C8)-alkoxy can be unsubstituted or substituted with one or more groups independently selected from the group consisting of halogen, hydroxy, oxo, cyano, (C1-C8)-alkynyl, (C1-C8)-alkoxy, (C3-C12)-cycloalkyl, (C6-C10)-aryl, heterocyclyl, heteroaryl, halo(C1-C8)alkoxy, C(O)Rh, OC(O)Rh, COORh, C(O)NRhRi, O—Ri, OC(O)NRhRi, NRhRi, NRhC(O)Ri, NRhC(O)NRhRi, S(O)q(C1-C8)-alkyl, S(O)rNRhRi and NRhS(O)qRi;
• each of the (C3-C12)-cycloalkyl, (C5-C10)-cycloalkenyl and (C6-C10)-aryl can be unsubstituted or substituted with one or more groups independently selected from the group consisting of halogen, hydroxy, oxo, cyano, (C1-C8)-alkyl, (C1-C8)-alkoxy, (C3-C12)-cycloalkyl, (C6-C10)-aryl, heterocyclyl, heteroaryl, halo(C1-C8)alkyl, halo(C1-C8)alkoxy, C(O)Rh, COORh, C(O)NRhRi, O—Ri, OC(O)Rh, OC(O)NRhRi, NRhRi, NRhC(O)Ri, NRhC(O)NRhRi, S(O)q(C1-C8)-alkyl, S(O)rNRhRi and NRhS(O)qRi;
• heterocyclyl is a 3- to 10-membered ring containing 1, 2, 3 or 4 heteroatoms independently selected from the group consisting of N, S and O, wherein said heterocyclyl is unsubstituted or substituted with one or more groups independently selected from the group consisting of halogen, hydroxy, oxo, cyano, (C1-C8)-alkyl, (C1-C8)-alkoxy, (C3-C12)-cycloalkyl, (C6-C10)-aryl, heterocyclyl, heteroaryl, halo(C1-C8)alkyl, halo(C1-C8)alkoxy, C(O)Rh, COORh, C(O)NRhRi, O—Ri, OC(O)Rh, OC(O)NRhRi, NRhRi, NRhC(O)Ri, NRhC(O)NRhRi, S(O)q(C1-C8)-alkyl, S(O)rNRhRi and NRhS(O)qRi;
• heteroaryl is a 5- to 10-membered ring containing 1, 2, 3 or 4 heteroatoms independently selected from the group consisting of N, S and O, wherein said heteroaryl is unsubstituted or substituted with one or more groups independently selected from the group consisting of halogen, hydroxy, oxo, cyano, (C1-C8)-alkyl, (C1-C8)-alkoxy, (C3-C12)-cycloalkyl, (C6-C10)-aryl, heterocyclyl, heteroaryl, halo(C1-C8)alkyl, halo(C1-C8)alkoxy, C(O)Rh, COORh, C(O)NRhRi, O—Ri, OC(O)Rh, OC(O)NRhRi, NRhRi, NRhC(O)Ri, NRhC(O)NRhRi, S(O)q(C1-C8)-alkyl, S(O)rNRhRi and NRhS(O)qRi;
• and
• Rh and R1 are independently selected from the group consisting of hydrogen, (C1-C8)-alkyl, (C2-C8)-alkenyl, halo(C1-C8)alkyl, (C3-C12)-cycloalkyl, (C6-C10)-aryl, (C6-C10)-aryl-(C1-C8)-alkyl, heteroaryl and heterocyclyl;
• provided that,
• (i) when R1 is —S(O)rNRbRc, wherein Rb and Rc can combine to form a saturated or unsaturated 5- or 6-membered ring, then Q is
• is
• (ii) when R1 is NRbCORc, wherein Rb is hydrogen and R is (C1-C8)-alkyl, then Q is
• or an isotopic form, a stereoisomer or tautomer thereof;
• or a pharmaceutically acceptable salt, a solvate, a polymorph, a prodrug, S-oxide or N-oxide thereof.