Aryl sultam derivatives as RORc modulators

A compound of formula I:

• or a pharmaceutically acceptable salt thereof,
• wherein:
• m is 0 or 1;
• n is 0 or 1;
• p is from 0 to 3;
• q is 0, 1 or 2;
• r is from 1 to 3;
• A is:
• a bond;
• —(CRjRk)t—;
• —C(O)—(CRjRk)t—;
• —(CRjRk)t—C(O)—;
• —NRa—(CRjRk)t—;
• —(CRjRk)t—NRa—;
• —C(O)NRa—(CRjRk)t;
• —(CRjRk)t—NRaC(O)—;
• —O—(CRjRk)t—;
• —(CRjRk)t—O—;
• —S—(CRjRk)t;
• —(CRjRk)t—S—;
• —SO2—(CRjRk)t;
• or —(CRjRk)t—SO2—;
• t is from 0 to 4;
• W is:
• —CRbRc—;
• —O—;
• —S—;
• —SO2—;
• or —NRd—;
• one of X1, X2, X3 and X4 is N and the others are CRe;
• or two of X1, X2, X3 and X4 are N and the others are CRe;
• or three of X1, X2, X3 and X4 are N and the other is CRe;
• or each of X1, X2, X3 and X4 is CRe;
• Y is:
• —O—;
• —S—;
• SO2—;
• —CRfRg—;
• or —NRh—;
• Z is:
• CH;
• or N;
• R1, R2, R3, R4, R5, R6, R7 and R8 each independently is:
• hydrogen;
• or C1-6alkyl which may be unsubstituted or substituted one or more times with halo;
• or R3 and R4 together with the atom to which they are attached may form an ethylene group;
• or R3 and R4 together with the atoms to which they are attached may form a three, four, five, six or seven membered saturated or partially saturated ring that may optionally include one or two heteroatoms selected from —O—, —NRa- or —S—, and which may be optionally substituted one or more times with R′;
• or R5 and R6 together with the atoms to which they are attached may form a three, four, five, six or seven membered saturated or partially saturated ring that may optionally include one or two heteroatoms selected from —O—, —NRa- or —S—, and which may be optionally substituted one or more times with R′;
• or R7 and R8 together with the atoms to which they are attached may form a three, four, five, six or seven membered saturated or partially saturated ring that may optionally include one or two heteroatoms selected from —O—, —NRa- or —S—, and which may be optionally substituted one or more times with Ri;
• or one of R3 and R4 together with one of R5 and R6 and the atoms to which they are attached may form a three, four, five, six or seven membered saturated or partially saturated ring that may optionally include one or two heteroatoms selected from —O—, —NRa- or —S—, and which may be optionally substituted one or more times with Ri;
• or one of R5 and R6 together with one of R7 and R8 and the atoms to which they are attached may form a three, four, five, six or seven membered saturated or partially saturated ring that may optionally include one or two heteroatoms selected from —O—, —NRa- or —S—, and which may be optionally substituted one or more times with Ri;
• each R9 is independently:
• C1-6alkyl;
• halo;
• C1-6alkoxy;
• or cyano;
• wherein the C1-6alkyl moieties may be unsubstituted or substituted one or more times with halo;
• R10 is:
• hydrogen;
• carboxy;
• C1-6alkyl-carbonyl;
• C1-6alkoxy-carbonyl;
• oxo;
• hydroxy;
• aminocarbonyl;
• N—C1-6alkyl-aminocarbonyl;
• N,N-di-C1-6alkyl-aminocarbonyl;
• cyano;
• hydroxy-C16alkyl;
• N—C1-6alkoxy-C1-6alkyl-aminocarbonyl;
• N-hydroxy-C1-6alkyl-aminocarbonyl;
• N—C1-6alkoxy-aminocarbonyl;
• halo;
• or C1-6alkyl which may be unsubstituted or substituted one or more times with halo or oxo;
• R11 is:
• hydrogen;
• halo;
• carboxy;
• C1-6alkyl-carbonyl;
• C1-6alkoxy-carbonyl;
• oxo;
• hydroxy;
• aminocarbonyl;
• N—C1-6alkyl-aminocarbonyl;
• N,N-di-C1-6alkyl-aminocarbonyl;
• C1-6alkyl-sulfonylamino;
• C1-6alkyl-sulfonylamino-C1-6alkyl;
• cyano;
• hydroxy-C16alkyl;
• N—C1-6alkoxy-C1-6alkyl-aminocarbonyl;
• N-hydroxy-C1-6alkyl-aminocarbonyl;
• N—C1-6alkoxy-aminocarbonyl;
• or C1-6alkyl which may be unsubstituted or substituted one or more times with halo or oxo;
• R12 is:
• hydrogen;
• halo;
• carboxy;
• C1-6alkyl-carbonyl;
• C1-6alkoxy-carbonyl;
• oxo;
• hydroxy;
• aminocarbonyl;
• N—C1-6alkyl-aminocarbonyl;
• N,N-di-C1-6alkyl-aminocarbonyl;
• cyano;
• hydroxy-C16alkyl;
• N—C1-6alkoxy-C1-6alkyl-aminocarbonyl;
• N-hydroxy-C1-6alkyl-aminocarbonyl;
• N—C1-6alkoxy-aminocarbonyl;
• or C1-6alkyl which may be unsubstituted or substituted one or more times with halo or oxo;
• Ra, Rb, Rc and Rd each independent is:
• hydrogen;
• or C1-6alkyl which may be unsubstituted or substituted one or more times with halo;
• or Rb and Rc together with the atoms to which they are attached may form a three, four, five, six or seven membered saturated or partially saturated ring that may optionally include one or two heteroatoms selected from —O—, —NRa- or —S—, and which may be optionally substituted one or more times with Ri;
• or one of Rb and Rc together with one of R7 and R8 and the atoms to which they are attached may form a three, four, five, six or seven membered saturated or partially saturated ring that may optionally include one or two heteroatoms selected from —O—, —NRa- or —S—, and which may be optionally substituted one or more times with Ri;
• or one of Rb and Rc together with one of R5 and R6 and the atoms to which they are attached may form a three, four, five, six or seven membered saturated or partially saturated ring that may optionally include one or two heteroatoms selected from —O—, —NRa- or —S—, and which may be optionally substituted one or more times with Ri;
• each Re is independently:
• hydrogen;
• C1-6alkyl;
• halo;
• C1-6alkoxy;
• or cyano;
• wherein the C1-6alkyl moieties may be unsubstituted or substituted one or more times with halo;
• Rf is:
• hydrogen;
• halo;
• or C1-6alkyl which may be unsubstituted or substituted one or more times with halo;
• Rg is:
• hydrogen;
• C1-6alkyl;
• C3-6cycloalkyl;
• C3-6cycloalkenyl;
• C3-6cycloalkyl-C1-6alkyl;
• halo;
• C1-6alkyl-carbonyl;
• C3-6cycloalkyl-carbonyl;
• C3-6cycloalkyl-C1-6alkyl-carbonyl;
• cyano-C1-6alkyl-carbonyl;
• hydroxy-C1-6alkyl-carbonyl;
• C1-6alkoxy-C1-6alkyl-carbonyl;
• carboxy;
• N-cyano-aminocarbonyl;
• N-cyano-N—C1-6alkyl-aminocarbonyl;
• N—C1-6alkyl-acetimidamidyl;
• N,N′-di-C1-6alkyl-acetimidamidyl;
• N′-cyano-N—C1-6alkyl-acetimidamidyl;
• N′-hydroxy-acetimidamidyl;
• N′—C1-6alkoxy-acetimidamidyl;
• N′-hydroxy-N—C1-6alkyl-acetimidamidyl;
• N′—C1-6alkoxy-N—C1-6alkyl-acetimidamidyl;
• 2-nitro-1-N—C1-6alkylamino-vinyl;
• formyl;
• C1-6alkyl-sulfonyl;
• C3-6cycloalkyl-sulfonyl;
• C3-6cycloalkyl-C1-6alkyl-sulfonyl;
• C1-6alkyl-sulfonyl-C1-6alkyl;
• aminocarbonyl;
• N-hydroxy-aminocarbonyl;
• N—C1-6alkoxy-aminocarbonyl;
• N—C1-6alkyl-aminocarbonyl;
• aminocarbonyl-C1-6alkyl;
• N—C1-6alkyl-aminocarbonyl-C1-6alkyl;
• N,N-di-C1-6alkyl-aminocarbonyl-C1-6alkyl;
• C1-6alkoxy-carbonyl;
• N-hydroxy-N—C1-6alkyl-aminocarbonyl;
• N—C1-6alkoxy-N—C1-6alkyl-aminocarbonyl;
• N,N-di-C1-6alkyl-aminocarbonyl;
• aminosulfonyl;
• N—C1-6alkyl-aminosulfonyl;
• N,N-di-C1-6alkyl-aminosulfonyl;
• cyano;
• C1-6alkoxy;
• C1-6alkyl-sulfonylamino;
• N—C1-6alkyl-sulfonylaminocarbonyl;
• N—(C1-6alkyl-sulfonyl)-N—C1-6alkyl-aminocarbonyl;
• N—(C1-6alkyl-sulfonyl)-amino-C1-6alkyl;
• amino;
• N—C1-6alkyl-amino;
• N,N-di-C1-6alkyl-amino;
• halo-C1-6alkyl;
• heterocyclyl;
• heteroaryl;
• or hydroxyl;
• wherein the C1-6alkyl moieties may be unsubstituted or substituted one or more times with halo;
• and wherein the heterocyclyl, heteroaryl, C3-6cycloalkyl, C3-6cycloalkenyl and C3-6cycloalkyl-C1-6alkyl moieties may be unsubstituted or substituted one or more times with Ri;
• or Rf and Rg together with the atoms to which they are attached may form a four, five, six or seven membered saturated or partially saturated ring that may optionally include one or two heteroatoms selected from —O—, —NRa- or —S—, and which may be optionally substituted one or more times with R′;
• Rh is:
• hydrogen;
• C1-6alkyl;
• C3-6cycloalkyl;
• C3-6cycloalkenyl;
• C3-6cycloalkyl-Ci-6alkyl;
• C1-6alkyl-carbonyl;
• C3-6cycloalkyl-carbonyl;
• C3-6cycloalkyl-C1-6alkyl-carbonyl;
• cyano-C1-6alkyl-carbonyl;
• hydroxy-C1-6alkyl-carbonyl;
• C1-6alkoxy-C1-6alkyl-carbonyl;
• N-cyano-aminocarbonyl;
• N-cyano-N—C1-6alkyl-aminocarbonyl;
• N—C1-6alkyl-acetimidamidyl;
• N,N′-di-C1-6alkyl-acetimidamidyl;
• N′-cyano-N—C1-6alkyl-acetimidamidyl;
• N′-hydroxy-acetimidamidyl;
• N′—C1-6alkoxy-acetimidamidyl;
• N′-hydroxy-N—C1-6alkyl-acetimidamidyl;
• N′—C1-6alkoxy-N—C1-6alkyl-acetimidamidyl;
• 2-nitro-1-N—C1-6alkylamino-vinyl;
• formyl;
• C1-6alkyl-sulfonyl;
• C3-6cycloalkyl-sulfonyl;
• C3-6cycloalkyl-C1-6alkyl-sulfonyl;
• C1-6alkyl-sulfonyl-C1-6alkyl;
• aminocarbonyl;
• N-hydroxy-aminocarbonyl;
• N—C1-6alkoxy-aminocarbonyl;
• N—C1-6alkyl-aminocarbonyl;
• N-hydroxy-N—C1-6alkyl-aminocarbonyl;
• N— C1-6alkoxy-N—C1-6alkyl-aminocarbonyl;
• N,N-di-C1-6alkyl-aminocarbonyl;
• aminosulfonyl;
• N—C1-6alkyl-aminosulfonyl;
• N,N-di-C1-6alkyl-aminosulfonyl;
• cyano;
• C1-6alkyl-sulfonylamino;
• sulfonylamino-C1-6alkyl;
• N—(C1-6alkyl-sulfonyl)aminocarbonyl;
• N—(C1-6alkyl-sulfonyl)-N—C1-6alkyl-aminocarbonyl;
• N—(C1-6alkyl-sulfonyl)-amino-C1-6alkyl;
• aminocarbonyl-C1-6alkyl;
• N—C1-6alkyl-aminocarbonyl-C1-6alkyl;
• N,N-di-C1-6alkyl-aminocarbonyl-C1-6alkyl;
• C1-6alkoxy-carbonyl;
• halo-C1-6alkyl;
• heterocyclyl;
• or heteroaryl;
• wherein the C1-6alkyl moieties may be unsubstituted or substituted one or more times with halo;
• and wherein the heterocyclyl, heteroaryl, C3-6cycloalkyl, C3-6cycloalkenyl and C3-6cycloalkyl-C1-6alkyl moieties may be unsubstituted or substituted one or more times with Ri;
• or Rh and one of R10 and R11 together with the atoms to which they are attached may form a four, five, six or seven membered aromatic, partially saturated or unsaturated ring that may optionally include one or two additional heteroatom selected from —O—, —NRa- or —S—, and which may be optionally substituted one or more times with Ri—;
• Ri is:
• C1-6alkyl;
• halo;
• oxo;
• hydroxy;
• acetyl;
• C1-6alkyl-carbonyl;
• amino-carbonyl;
• hydroxy-C1-6alkyl;
• cyano;
• heteroaryl;
• or C1-6alkoxy;
• wherein the C1-6alkyl moieties may be unsubstituted or substituted one or more times with halo;
• and
• Rj and Rk each independent is:
• hydrogen;
• or C1-6alkyl which may be unsubstituted or substituted one or more times with halo.