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1. (WO2015104354) ARYL SULTAM DERIVATIVES AS RORc MODULATORS
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CLAIMS

What is claimed is:

1. A compound


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 ;

-C(0)-(CRjRk)r;

-(CRjRk)rC(0)-;

-NRa-(CRjRk)r;

-(CRjRk)t-NRa-;

-C(0)NRa-(CRjRk)t-;

-(CRjRk)rNRaC(0)-;

-0-(CRjRk)r;

-(CRjRk)rO-;

-S-(CRjRk)r;

-(CRjRk -S-;

-SOHCRjRk -;

-(CRjRk)rS02-; or

t is from 0 to 4;

W is:

-CRbRc-;

-0-;

-S-;

-S02-; 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:

-0-;

-S-;

-S02-;

-CRfRg-; or

-NRh-;

Z is: CRm;

R1, R2, R3, R4, R5, R6, R7 and R8 each independently is:

hydrogen; or Ci_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 -0-, -NRa- or -S-, and which may be optionally substituted one or more times with R1; 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 -0-, -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 -0-, -NRa- or -S-, and which may be optionally substituted one or more times with R';

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 -0-, -NRa- or -S-, and which may be optionally substituted one or more times with R1;

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 -0-, -NRa- or -S-, and which may be optionally substituted one or more times with R1;

each R9 is independently:

C!.6alkyl;

halo;

C^alkoxy; or

cyano;

wherein the Ci_6aikyl moieties may be unsubstituted or substituted one or more times with halo;

R10 is:

hydrogen;

carboxy;

Ci_6alkyl-carbonyl;

Ci_6aikoxy-carbonyl;

oxo;

hydroxy;

aminocarbonyl;

N-C ^alkyl-aminocarbonyl ;

N^-di-C!^alkyl-aminocarbonyl;

cyano;

hydroxy-C i .6alkyl ;

N-C !.6alkoxy-C !^alkyl-aminocarbonyl ;

N-hydroxy-C!^alkyl-aminocarbonyl;

N-C ^alkoxy-aminocarbonyl ;

halo; or

Ci_6alkyl which may be unsubstituted or substituted one or more times with halo or oxo;

R11 is:

hydrogen;

halo;

carboxy;

Ci_6alkyl-carbonyl;

C !^alkoxy-carbonyl ;

oxo;

hydroxy;

aminocarbonyl;

N-C !^alkyl-aminocarbonyl ;

N,N-di-Ci_6alkyl-aminocarbonyl;

C^alkyl-sulfonylamino;

C!^alkyl-sulfonylamino-C!^alkyl;

cyano;

hydroxy-C i .6alkyl ;

N-C i_6alkoxy-C i.6alkyl-aminocarbonyl ;

N-hydroxy-Ci.6alkyl-aminocarbonyl;

N-Ci_6alkoxy-aminocarbonyl; or

Ci_6alkyl which may be unsubstituted or substituted one or more times with halo or oxo; or R10 and R11 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 -0-, -NRa- or -S-, and which may be optionally substituted one or more times with R';

or R10 and R11 together with the atoms to which they are attached may form a double bond; R12 is:

hydrogen;

halo;

carboxy;

Ci_6alkyl-carbonyl;

C^alkoxy-carbonyl;

oxo;

hydroxy;

aminocarbonyl;

N-C !^alkyl-aminocarbonyl ;

N,N-di-Ci.6alkyl-aminocarbonyl;

cyano;

hydroxy-C i _6alkyl ;

N-C i_6alkoxy-C i_6alkyl-aminocarbonyl ;

N-hydroxy-Ci_6alkyl-aminocarbonyl;

N-Ci_6alkoxy-aminocarbonyl; or

which may be unsubstituted or substituted one or more times with halo or oxo;

R13 is:

hydrogen; or

Ci_6alkyl which may be unsubstituted or substituted one or more times with halo;

Ra, Rb, Rc and Rd each independent is:

hydrogen; or


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 -0-, -NRa- or -S-, and which may be optionally substituted one or more times with R';

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 -0-, -NRa- or -S-, and which may be optionally substituted one or more times with R1;

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 -0-, -NRa- or -S-, and which may be optionally substituted one or more times with R1;

each Re is independently:

hydrogen;

d.ealkyl;

halo;

C!.6alkoxy; or

cyano;

wherein the C^ancyl moieties may be unsubstituted or substituted one or more times with halo, hydroxy or Ci_6aikoxy;

Rf is:

hydrogen;

halo;

C!.6alkoxy; or

Ci_6alkyl which may be unsubstituted or substituted one or more times with halo, hydroxy, or Ci_6alkoxy;

Rg is:

hydrogen;

Ci-6alkyl;

C3.6cycloalkyl;

C3.6cycloalkenyl;

Cs^cycloalkyl-C ealkyl;

halo;

C^alkyl-carbonyl;

C3_6cycloalkyl-carbonyl;

C3.6cycloalkyl-Ci_6alkyl-carbonyl;

cyano-Ci_6alkyl-carbonyl;

hydroxy-Ci_6alkyl-carbonyl;

Ci.6alkoxy-Ci_6alkyl-carbonyl;

carboxy;

N-cyano-aminocarbonyl ;

N-cyano-N-Ci_6alkyl-aminocarbonyl;

N-C !^alkyl-acetimidamidyl ;

N,N'-di-Ci.6alkyl-acetimidamidyl;

N'-cyano-N-Ci_6alkyl-acetimidamidyl;

N'-hydroxy-acetimidamidyl ;

N'- C!^alkoxy-acetimidamidyl;

N'-hydroxy-N-Ci.6alkyl-acetimidamidyl;

N'-C i_6alkoxy- N-C !^alkyl-acetimidamidyl;

2-nitro- 1 -N-C ^alkylamino-vinyl; formyl ;


C3.6cycloalkyl-sulfonyl ;

C3_6cycloalkyl-Ci.6alkyl-sulfonyl;

Ci.6alkyl-sulfonyl-Ci_6alkyl;

aminocarbonyl;

carbonylamino;

N-hydroxy-aminocarbonyl ;

N-C !^alkoxy-aminocarbonyl ;

N-C !^alkyl-aminocarbonyl ;

aminocarbonyl-Ci_6alkyl;

N-C!^alkyl-aminocarbonyl-C!^alkyl;

N^-di-C!^alkyl-aminocarbonyl-C!^alkyl;

C^alkoxy-carbonyl;

N-hydroxy-N-C ^alkyl-aminocarbonyl ;

N- Ci_6alkoxy-N-Ci_6alkyl-aniinocarbonyl;

N^-di-C!^alkyl-aminocarbonyl;

aminosulfonyl;

N-C ^alkyl-aminosulfonyl ;

N,N-di-Ci.6alkyl-aniinosulfonyl;

cyano;

Ci_6alkoxy;

Ci.6alkyl-sulfonylamino;

N-Ci.6alkyl-sulfonylaminocarbonyl;

N-(Ci_6alkyl-sulfonyl)-N-Ci_6alkyl-aniinocarbonyl;

N-(Ci.6alkyl-sulfonyl)-amino-Ci_6alkyl; amino;

N-C i.6alkyl-amino ;

N,N-di-Ci.6alkyl-amino;

halo-Ci_6alkyl;

phenyl;

heterocyclyl;

heteroaryl;

Ci_6alkyl-carbonylamino;

carbonylamino; or

hydroxy;

wherein the C^alkyl moieties may be unsubstituted or substituted one or more times with halo; and

wherein the phenyl, heterocyclyl, heteroaryl, C3.6cycloalkyl, C3.6cycloalkenyl and C3_ 6cycloalkyl-Ci_6alkyl moieties may be unsubstituted or substituted one or more times with R1; or Rf and Rs together may form oxo;

or Rf and Rs 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 -0-, -NRa- or -S-, and which may be optionally substituted one or more times with R1; hydrogen;

Ci-6alkyl;

C3.6cycloalkyl;

C3.6cycloalkenyl;

C3.6cycloalkyl-Ci_6alkyl;

Ci_6alkyl-carbonyl;

C3.6cycloalkyl-carbonyl;

C^ecycloalkyl-C!^alkyl-carbonyl;

cyano-C^alkyl-carbonyl;

hydroxy-Ci_6alkyl-carbonyl;

Ci.6alkoxy-Ci_6alkyl-carbonyl;

N-cyano-aminocarbonyl ;

N-cyano-N-Ci.6alkyl-aminocarbonyl;

N-C !^alkyl-acetimidamidyl ;

N,N'-di-Ci_6alkyl-acetimidamidyl;

N'-cyano-N-Ci_6alkyl-acetimidamidyl;

N'-hydroxy-acetimidamidyl ;

N'- Ci_6alkoxy-acetimidamidyl;

N'-hydroxy-N-C i.6alkyl-acetimidamidyl ;

N'-C i_6alkoxy- N-C !^alkyl-acetimidamidyl;

2-nitro- 1 -N-C ^alkylamino-vinyl;

formyl;

Ci_6alkyl-sulfonyl;

C3.6cycloalkyl-sulfonyl ;

Cs^cycloalkyl-C!^alkyl-sulfonyl;

C!^alkyl-sulfonyl-C!^alkyl;

aminocarbonyl;

N-hydroxy-aminocarbonyl ;

N-C !^alkoxy-aminocarbonyl ;

N-C !^alkyl-aminocarbonyl ;

N-hydroxy-N-C ^alkyl-aminocarbonyl ;

N- C!^alkoxy-N-C!^alkyl-aminocarbonyl;

N,N-di-Ci_6alkyl-aniinocarbonyl;

aminosulfonyl;

N-C !^alkyl-aminosulfonyl ;

N^-di-C!^alkyl-aminosulfonyl;

cyano;

C!^alkyl-sulfonylamino;

Ci_6alkyl-sulfonylamino-Ci_6alkyl;

N-(Ci.6alkyl-sulfonyl)aniinocarbonyl;

N-(C1.6alkyl-sulfonyl)-N-C1.6alkyl-aminocarbonyl;

N^C!^alkyl-sulfony^-amino-C!^alkyl;

aminocarbonyl-C!^alkyl;

N-Ci_6alkyl-aniinocarbonyl-Ci_6alkyl;

N,N-di-Ci_6alkyl-aniinocarbonyl-Ci_6alkyl;

Ci_6alkoxy-carbonyl;

phenyl;

heterocyclyl; or

heteroaryl;

wherein the Ci_6alkyl moieties may be unsubstituted or substituted one or more times with halo; and

wherein the phenyl, heterocyclyl, heteroaryl, C3.6cycloalkyl, C3.6cycloalkenyl and C3_

6cycloalkyl-Ci_6alkyl moieties may be unsubstituted or substituted one or more times with R1; 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 -0-, -NRa- or -S-, and which may be optionally substituted one or more times with R1 -;

or one of Rf and Rs and one of R10 and R11 together with the atoms to which they are attached may form a three, four, five, six or seven membered aromatic, partially saturated or unsaturated ring that may optionally include an additional heteroatom selected from -0-, -NRa- or -S-, and which may be optionally substituted one or more times with R1;

R' is:

d.ealkyl;

halo-Ci_6aikyl;

C3.6cycloalkyl;

halo;

oxo;

hydroxy;

acetyl;

C^alkyl-carbonyl;

amino-carbonyl;

hydroxy-C i _6alkyl ;

cyano;

cyano-Ci_6alkyl;


carboxy; or

C^alkoxy;

Rj and Rk each independent is:

hydrogen; or

Ci_6alkyl which may be unsubstituted or substituted one or more times with halo; and Rm is: d_6alkyl;

hydroxy;

halo;

hydroxy-C i _6alkyl ;

Ci.6alkylsulfonyl-Ci_6alkyl;

cyano;

Ci_6alkylsulfonyl-amino- Ci_6alkylsulfinyl-amino- cyano-C^alkyl;

cyano-C2_6alkenyl ;

amino-Ci_6alkyl;

Ci.6alkoxy-Ci.6alkyl;

C!^alkoxy-C!^alkoxy-C!^alkyl;

hydroxy-C i _6alkoxy ;

hydroxy-C!^alkoxy-C!^alkyl;

hydroxy-Ci_6alkyl-amino;

Ci_6alkoxy-Ci_6alkyl-amino;

N-hydroxy-carboxamidinyl ;

Ci.6alkoxy-carbonyl-C2-6alkenyl;

amino;

N-Ci_6alkylamino;

N,N-di-Ci-6alkylamino;

-(CHRl)u-C(0)-NRpRq;

-(CHRs)u-0-(CHRs)v-C(0)-NRpRq;

-(CHRs)u-NRn-(CHRs)v-C(0)- NRpRq

-(CHR')u-C(0)-Ru;

-(CHRs)u-0-(CHRs)v-C(0)-Ru; or

-(CHRs)u-NRn-(CHRs)v-C(0)- Ru;

u is from 0 to 2;

v is from 0 to 2;

each Rn is independently:

hydrogen; or

Ci_6alkyl;

Rp is:

hydrogen; or

Ci-ealkyl;

Rq is:

hydrogen;

C1-6alkyl;

hydroxy-Ci _6alkyl ;

N-(Ci_6alkylcarbonyl)-arrdno-Ci_6alkyl; Ci.6alkylsulfonyl-Ci.6alkyl;

amino-d^alkyl;


N,N-di-C ^alkylamino-C i_6alkyl ;

N,N-di-Ci-6alkylaminocarbonyl-Ci.6alkyl; cyano-Ci_6alkyl;

carboxy-C !^alkyl ;

aminocarbonyl-C!^alkyl;

N-Ci.6alkylaminocarbonyl-Ci.6alkyl; N,N-di-C i-6 lkyl aminocarbonyl-Ci_6alkyl; C i.6alkylsulfonyl-C i_6alkyl ; or

Ci.6alkoxy-Ci_6alkyl;

each Rs is independently:

hydrogen; or

Ci-6alkyl;

each Rl is independently:

hydrogen;

Ci-6alkyl;

halo; or

hydroxy; and

Ru is: d_6alkyl;

C!.6alkoxy;

hydroxy;

hydroxy-C i _6alkyl .

2. The compound of claim 1, wherein R1, R2, R4, R5, R6, R7, R8, R13, Ra, Rb and Rc are hydrogen.

3. The compound of claim 1 or 2, wherein X1, X2, X3 and X4 are CRe.

4. The compound of any of claims 1 to3, wherein p is 0.

5. The compound of any of claims lto 4, wherein m is 1.

6. The compound of any of claims lto 5 wherein n is 0.

7. The compound of any of claims lto 6 wherein A is: a bond; or -(CRjRkX-O-.

8. The compound of any of claims lto 7 wherein W is -CRbRc-.

9. The compound of any of claims lto 8 wherein Y is -0-, -CRfRs- or -NRh-.

10. The compound of any of claims lto 9, wherein R9 is halo.

11. The compound of any of claims lto 10, wherein R10 is: hydrogen; halo; or Ci_6alkyl which may be unsubstituted or substituted one or more times with halo or oxo.

12. The compound of any of claims lto 11, wherein R11 is: hydrogen; halo; or C^alkyl.

13. The compound of any of claims Ito 12, wherein, R is: hydrogen; or Ci_6alkyl.

14. The compound of any of claims Ito 13, wherein each Re is independently: hydrogen; or halo.

15. The compound of any of claims Ito 14, wherein Rm is selected from:

The compound of any of claims lto 15, wherein the compound is of formula II

The co formula VII


18. A composition comprising:

(a) a pharmaceutically acceptable carrier; and

(b) a compound of any of claims claim lto 18.

19. A method for treating psoriasis, said method comprising administering to a subject in need thereof an effective amount of a compound of any of claims claim lto 18.

20. A compound of claim of anyone of claims 1 to 18 for the treatment of arthritis, asthma,

COPD,psoriasis, lupus (Lupus erythematosus), Sjogren's disesase, irritable bowel disease, idiopathic pulmonary fibrosis or muscular sclerosis.

21. The use of a compound of anyone of claims 1 to 18 for treating arthritis, asthma, COPD,psoriasis, lupus (Lupus erythematosus), Sjogren's disesase, irritable bowel disease, idiopathic pulmonary fibrosis or muscular sclerosis.

22. The use of a compound of anyone of claims 1 to 18 for the preparation of a medicament for treating arthritis, asthma, COPD,psoriasis, lupus (Lupus erythematosus), Sjogren's disesase, irritable bowel disease, idiopathic pulmonary fibrosis or muscular sclerosis.

The invention as hereinbefore described.