Methods for treating arthritic disorders

1. A method of treatment of arthritic and rheumatic disorders in a mammal, the method comprising administering to a mammal in need thereof a pharmaceutically effective amount of a compound of the formula:

wherein:

R is selected from the formulae —(CH 2 ) n -A, —(CH 2 ) n —S-A, or —(CH 2 ) n —O-A, wherein A is selected from the moieties:

wherein

D is C 1 –C 6 lower alkyl, C 1 –C 6 lower alkoxy, C 3 –C 6 cylcoalkyl, —CF 3 or —(CH 2 ) 1-3 —CF 3 ;

B and C are independently selected from phenyl, pyridinyl, pyrimidinyl, furyl, thienyl or pyrrolyl groups, each optionally substituted by from 1 to 3, preferably 1 to 2, substituents selected independently from H, halogen, —CN, —CHO, —CF 3 , —OCF 3 , —OH, —C 1 –C 6 alkyl, C 1 –C 6 alkoxy, —NH 2 , —N(C 1 –C 6 ) 2 , —NH(C 1 –C 6 ), —N—C(O)—(C 1 –C 6 ), —NO 2 , or by a 5- or 6-membered heterocyclic or heteroaromatic ring containing 1 or 2 heteroatoms selected from O, N or S; or

n is an integer from 0 to 3;

n 1 is an integer from 1 to 3;

n 2 is an integer from 0 to 4;

n 3 is an integer from 0 to 3;

n 4 is an integer from 0 to 2;

X 1 is selected from a chemical bond, —S—, —O—, —S(O)—, —S(O) 2 —, —NH—, —NHC(O)—,

—C═C—,

R 1 is selected from C 1 –C 6 alkyl, C 1 –C 6 fluorinated alkyl, C 3 –C 6 cycloalkyl, tetrahydropyranyl, camphoryl, adamantyl, CN, —N(C 1 –C 6 alkyl) 2 , phenyl, pyridinyl, pyrimidinyl, furyl, thienyl, napthyl, morpholinyl, triazolyl, pyrazolyl, piperidinyl, pyrrolidinyl, imidazolyl, piperizinyl, thiazolidinyl, thiomorpholinyl, tetrazole, indole, benzoxazole, benzofuran, imidazolidine-2-thione, 7,7,dimethyl-bicyclo[2.2.1]heptan-2-one, Benzo[1,2,5]oxadiazole, 2-Oxa-5-aza-bicyclo[2.2.1]heptane, Piperazin-2-one or pyrrolyl groups, each optionally substituted by from 1 to 3, preferably 1 to 2, substituents independently selected from H, halogen, —CN, —CHO, —CF 3 , OCF 3 , —OH, —C 1 –C 6 alkyl, C 1 –C 6 alkoxy, —NH 2 , —N(C 1 –C 6 ) 2 , —NH(C 1 –C 6 ), —N—C(O)—(C 1 –C 6 ), —NO 2 , —SO 2 (C 1 –C 3 alkyl, —SO 2 NH 2 , —SO 2 NH(C 1 –C 3 alkyl), —SO 2 N(C 1 –C 3 alkyl) 2 , —COOH, —CH 2 —COOH, —CH 2 —N(C 1 –C 6 alkyl), —CH 2 —N(C 1 –C 6 alkyl) 2 , —CH 2 —NH 2 , pyridine, 2-Methyl-thiazole, morpholino, 1-Chloro-2-methyl-propyl, —C 1 –C 6 thioalkyl, phenyl (further optionally substituted with halogens), benzyloxy, (C 1 –C 3 alkyl)C(O)CH 3 , (C 1 –C 3 alkyl)OCH 3 , C(O)NH 2 , or

X 2 is selected from —O—, —CH 2 —, —S—, —SO—, —SO 2 —, —NH—, —C(O)—,

R 2 is a ring moiety selected from phenyl, pyridinyl, pyrimidinyl, furyl, thienyl or pyrrolyl groups, the ring moiety being substituted by a group of the formula —(CH 2 ) n4 —CO 2 H or a pharmaceutically acceptable acid mimic or mimetic; and also optionally substituted by 1 or 2 additional substituents independently selected from H, halogen, —CN, —CHO, —CF 3 , —OCF 3 , —OH, —C 1 –C 6 alkyl, C 1 –C 6 alkoxy, C 1 –C 6 thioalkyl, —NH 2 , —N(C 1 –C 6 ) 2 , —NH(C 1 –C 6 ), —N—C(O)—(C 1 –C 6 ), or —NO 2 ;

R 3 is selected from H, halogen, —CN, —CHO, —CF 3 , —OCF 3 , —OH, —C 1 –C 6 alkyl, C 1 –C 6 alkoxy, C 1 –C 6 thioalkyl, —NH 2 , —N(C 1 –C 6 ) 2 , —NH(C 1 –C 6 ), —N—C(O)—(C 1 –C 6 ), or —NO 2 ;

R 4 is selected from H, halogen, —CN, —CHO, —CF 3 , —OCF 3 , —OH, —C 1 –C 6 alkyl, C 1 –C 6 alkoxy, C 1 –C 6 thioalkyl, —NH 2 , —N(C 1 –C 6 ) 2 , —NH(C 1 –C 6 ), —N—C(O)—(C 1 –C 6 ), —NO 2 , —N—C(O)—N(C 1 –C 3 alkyl) 2 , —N—C(O)—NH(C 1 –C 3 alkyl), —N—C(O)—O—(C 1 –C 3 alkyl), —SO 2 —C 1 –C 6 alkyl, —S—C 3 –C 6 cycloalkyl, —S—CH 2 —C 3 –C 6 cycloalkyl, —SO 2 —C 3 –C 6 cycloalkyl, —SO 2 —CH 2 —C 3 –C 6 cycloalkyl, C 3 –C 6 cycloalkyl, —CH 2 —C 3 –C 6 cycloalkyl, —O—C 3 –C 6 cycloalkyl, —O—CH 2 —C 3 –C 6 cycloalkyl, phenyl, benzyl, benzyloxy, morpholino or other heterocycles such as pyrrolidino, piperidine, piperizine furan, thiophene, imidazole, tetrazole, pyrazine, pyrazolone, pyrazole, imidazole, oxazole or isoxazole, the rings of each of these R 4 groups each being optionally substituted by from 1 to 3 substituents selected from the group of H, halogen, —CN, —CHO, —CF 3 , —OH, —C 1 –C 6 alkyl, C 1 –C 6 alkoxy, —NH 2 , —N(C 1 –C 6 ) 2 , —NH(C 1 –C 6 ), —N—C(O)—(C 1 –C 6 ), —NO 2 , —SO 2 (C 1 –C 3 alkyl), —SO 2 NH(C 1 –C 3 alkyl), —SO 2 N(C 1 –C 3 alkyl) 2 , or OCF 3 ;

or a pharmaceutically acceptable salt form thereof.

2. A method of claim 1 wherein the pharmaceutically acceptable acid mimics or mimetics include those wherein R 2 is selected from the group consisting of:

wherein R a is selected from —CF 3 , —CH 3 , phenyl, or benzyl, with the phenyl or benzyl groups being optionally substituted by from 1 to 3 groups selected from C 1 –C 6 alkyl, C 1 –C 6 alkoxy, C 1 –C 6 thioalkyl, —CF 3 , halogen, —OH, or —COOH; R b is selected from —CF 3 , —CH 3 , —NH 2 , phenyl, or benzyl, with the phenyl or benzyl groups being optionally substituted by from 1 to 3 groups selected from C 1 –C 6 alkyl, C 1 –C 6 alkoxy, C 1 –C 6 thioalkyl, —CF 3 , halogen, —OH, or —COOH; and R c is selected from —CF 3 or C 1 –C 6 alkyl.

3. A method of claim 1 wherein A is the moiety:

and B, C, n, n1, n2, n3, n4, R, X 1 , X 2 , R 1 , R 2 , R 3 , and R 4 are as defined in claim 1 .

4. A method of claim 3 wherein B and C are unsubstituted phenyl, pyridinyl, pyrimidinyl, furyl, thienyl or pyrrolyl groups and R, n, n1, n2, n3, n4, R 1 , X 1 , X 2 , R 2 , R 3 , and R 4 are as defined in claim 1 .

5. A method of claim 1 wherein A is the moiety:

and n, n1, n2, n3, n4, R, X 1 , X 2 , R 1 , R 2 , R 3 , and R 4 are as defined in claim 1 .

6. A method of treatment of arthritic and rheumatic disorders in a mammal, the method comprising administering to a mammal in need thereof a pharmaceutically effective amount of a compound of formulae (II) or (III):

wherein n1, n2, n3, n4, X 1 , X 2 , R 1 , R 2 , R 3 , and R 4 are as defined in claim 1 , or a pharmaceutically acceptable salt thereof.

7. A method of claim 6 wherein n3=1, and n, n1, n2, n4, X 1 , X 2 , R 1 , R 2 , R 3 , and R 4 are as defined in claim 6 , or a pharmaceutically acceptable salt thereof.

8. A method of claim 6 wherein R 2 is phenyl substituted by a group of the formula —(CH 2 ) n4 —CO 2 H; and optionally substituted by 1 or 2 additional substituents independently selected from H, halogen, —CN, —CHO, —CF 3 , —OH, —C 1 –C 6 alkyl, C 1 –C 6 alkoxy, C 1 –C 6 thioalkyl, —NH 2 , —N(C 1 –C 6 ) 2 , —NH(C 1 –C 6 ), —N—C(O)—(C 1 –C 6 ), or —NO; and n1, n2, n4, R 1 , X 1 , X 2 , R 2 , R 3 , and R 4 are as defined in claim 6 , or a pharmaceutically acceptable salt thereof.

9. A method of treatment of arthritic and rheumatic disorders in a mammal, the method comprising administering to a mammal in need thereof a pharmaceutically effective amount of a compound of formulae (IV) or (V):

n 1 is an integer from 1 to 3;

n 2 is an integer from 1 to 3;

R 5 , R 6 and R 7 are independently selected from H, halogen, —CN, —CHO, —CF 3 , —OH, —C 1 –C 6 alkyl, C 1 –C 6 alkoxy, —NH 2 , —N(C 1 –C 6 ) 2 , —NH(C 1 –C 6 ), —N—C(O)—(C 1 –C 6 ), or —NO 2 ;

X 1 is selected from a chemical bond, —S—, —O—, —NH— or —N(C 1 –C 3 alkyl)-;

X 2 is selected from —O—, —SO 2 — or —CH 2 —;

R 2 is a moiety selected from the group of:

R 8 and R 9 are independently selected from H, halogen, —CN, —CHO, —CF 3 , —OH, —C 1 –C 6 alkyl, C 1 –C 6 alkoxy, —NH 2 , —N(C 1 –C 6 ) 2 , —NH(C 1 –C 6 ), —N—C(O)—(C 1 –C 6 ), or —NO 2 ;

n 4 is an integer from 0 to 2;

R 3 is selected from H, halogen, —CN, —CHO, —CF 3 , —OH, —C 1 –C 6 alkyl, C 1 –C 6 alkoxy, C 1 –C 6 thioalkyl, —NH 2 , —N(C 1 –C 6 ) 2 , —NH(C 1 –C 6 ), —N—C(O)—(C 1 –C 6 ), or —NO 2 ; and

R 4 is selected from H, halogen, —CN, —CHO, —CF 3 , —OH, —C 1 –C 6 alkyl, C 1 –C 6 alkoxy, C 1 –C 6 thioalkyl, —NH 2 , —N(C 1 –C 6 ) 2 , —NH(C 1 –C 6 ), —N—C(O)—(C 1 –C 6 ), —NO 2 , morpholino or other heterocycles such as pyrrolidino, piperidine, piperizine furan, thiophene, imidazole, tetrazole, pyrazine, pyrazolone, pyrazole, imidazole, oxazole or isoxazole;

or a pharmaceutically acceptable salt form thereof.

10. A method of treatment of arthritic and rheumatic disorders in a mammal, the method comprising administering to a mammal in need thereof a pharmaceutically effective amount of a compound of the formulae (VI) or (VII):

wherein:

X 1 is selected from a chemical bond, —S—, —O—, —NH— or —N(C 1 –C 3 alkyl)-;

X 2 is selected from —O—, —SO 2 —, or —CH 2 —;

R 3 is selected from H, halogen, —CN, —CHO, —CF 3 , —OH, —C 1 –C 6 alkyl, C 1 –C 6 alkoxy, C 1 –C 6 thioalkyl, —NH 2 , —N(C 1 –C 6 ) 2 , —NH(C 1 –C 6 ), —N—C(O)—(C 1 –C 6 ), or —NO 2 ; and

R 4 is selected from H, halogen, —CN, —CHO, —CF 3 , —OH, —C 1 –C 6 alkyl, C 1 –C 6 alkoxy, C 1 –C 6 thioalkyl, —NH 2 , —N(C 1 –C 6 ) 2 , —NH(C 1 –C 6 ), —N—C(O)—(C 1 –C 6 ), —NO 2 , morpholino or other heterocycles such as pyrrolidino, piperidine, piperizine furan, thiophene, imidazole, tetrazole, pyrazine, pyrazolone, pyrazole, imidazole, oxazole or isoxazole;

n 1 is an integer from 1 to 2;

n 2 is an integer from 1 to 2;

R 5 , R 6 and R 7 are independently selected from H, halogen, —CN, —CHO, —CF 3 , OCF 3 , —OH, —C 1 –C 6 alkyl, C 1 –C 6 alkoxy, —NH 2 , —N(C 1 –C 6 ) 2 , —NH(C 1 –C 6 ), —N—C(O)—(C 1 –C 6 ), or —NO 2 ;

R 8 and R 9 are independently selected from H, halogen, —CN, —CHO, —CF 3 , —OH, —C 1 –C 6 alkyl, C 1 –C 6 alkoxy, —NH 2 , —N(C 1 –C 6 ) 2 , —NH(C 1 –C 6 ), —N—C(O)—(C 1 –C 6 ), or —NO 2 ;

or a pharmaceutically acceptable salt form thereof.

11. A method of claim 10 of formulae (VI) or (VII) wherein: n 1 is 1; n 2 is 1; and X 1 , X 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 and R 9 are as defined in claim 10 , or a pharmaceutically acceptable salt form thereof.

12. A method of claim 1 , wherein X 1 is a chemical bond and n 1 , n 2 , X 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 and R 9 are as defined in claim 1 , or a pharmaceutically acceptable salt form thereof.

13. A method of claim 1 , wherein X 1 is a chemical bond and B, C, n, n 1 , n 2 , n 3 , n 4 , R, X 1 , X 2 , R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 and R 9 are as defined in claim 1 , or a pharmaceutically acceptable salt form thereof.

14. A method of claim 6 of formulae (II) or (III) wherein: X 1 is a chemical bond and n 1 , n 2 , n 3 , n 4 , X 1 , X 2 , R 1 , R 2 , R 3 and R 4 are as defined in claim 1 , or a pharmaceutically acceptable salt form thereof.

15. A method of claim 9 of formulae (IV) or (V) wherein: X 1 is a chemical bond and n 1 , n 2 , n 4 , X 1 , X 2 , R 2 , R 3 and R 4 , R 5 , R 6 , R 7 , R 8 , R 9 are as defined in claim 9 , or a pharmaceutically acceptable salt form thereof.

16. A method of claim 10 , wherein X 1 is a chemical bond and n 1 , n 2 , X 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 and R 9 are as defined in claim 10 , or a pharmaceutically acceptable salt form thereof.

17. A method of claim 1 wherein the compound is selected from the group consisting of:

4-[2-(1-Benzhydryl-2-{2-[(benzylsulfonyl)amino]ethyl}-5-chloro-1H-indol-3-yl)ethoxy]benzoic acid;

4-[2-(1-Benzhydryl-5-chloro-2-{2-[(isopropylsulfonyl)amino]ethyl}-1H-indol-3-yl)ethoxy]benzoic acid;

4-[2-(1-Benzhydryl-2-{2-[(butylsulfonyl)amino]ethyl}-5-chloro-1H-indol-3-yl)ethoxy]benzoic acid;

4-{2-[1-Benzhydryl-5-chloro-2-(2-{[(1-methyl-1H-imidazol-4-yl)sulfonyl]amino}ethyl)-1H-indol-3-yl]ethoxy}benzoic acid; and

4-{2-[1-Benzhydryl-2-(2-{[(5-bromo-6-chloro-3-pyridinyl)sulfonyl]amino}ethyl)-5-chloro-1H-indol-3-yl]ethoxy}benzoic acid;

and a pharmaceutically acceptable salt form thereof.

18. A method of claim 1 wherein the compound is selected from the group consisting of:

4-[2-(1-Benzhydryl-5-chloro-2-{2-[({[(1R)-7,7-dimethyl-2-oxobicyclo[2.2.1]hept-1-yl]methyl}sulfonyl)amino]ethyl}-1H-indol-3-yl)ethoxy]benzoic acid;

4-(2-{1-Benzhydryl-5-chloro-2-[2-({[(methylsulfonyl)methyl]sulfonyl}amino)ethyl]-1H-indol-3-yl}ethoxy)benzoic acid;

4-(2-{1-Benzhydryl-5-chloro-2-[2-({[(2-(1-naphthyl)ethyl]sulfonyl}amino)ethyl]-1H-indol-3-yl}ethoxy)benzoic acid;

4-{2-[1-Benzhydryl-5-chloro-2-{2-[({2-nitrobenzyl}-sulfonyl)amino]ethyl}-1H-indol-3-yl)ethoxy]benzoic acid; and

4-{2-[1-Benzhydryl-5-chloro-2-(2-{[(3,4-dichlorobenzyl)sulfonyl]amino}-ethyl)-1H-indol-3-yl]ethoxy}benzoic acid;

and a pharmaceutically acceptable salt form thereof.

19. A method of claim 1 wherein the compound is selected from the group consisting of:

4-{2-[1-Benzhydryl-5-chloro-2-(2-{[(3,5-dichlorobenzyl)sulfonyl]amino}-ethyl)-1H-indol-3-yl]ethoxy}benzoic acid;

4-(2-{1-Benzhydryl-5-chloro-2-(2-({[(3-(trifluoromethyl)benzyl]sulfonyl}-amino)ethyl]-1H-indol-3-yl}ethoxy)benzoic acid;

4-(2-{1-Benzhydryl-5-chloro-2-(2-({[(4-(trifluoromethyl)benzyl]sulfonyl}-amino)ethyl]-1H-indol-3-yl}ethoxy)benzoic acid;

4-{2-[1-Benzhydryl-5-chloro-2-(2-{[(4-fluorobenzyl)sulfonyl]amino}-ethyl)-1H-indol-3-yl]ethoxy}benzoic acid; and

4-{2-[1-Benzhydryl-5-chloro-2-(2-{[(4-chlorobenzyl)sulfonyl]amino}-ethyl)-1H-indol-3-yl]ethoxy}benzoic acid;

and a pharmaceutically acceptable salt form thereof.

20. A method of claim 1 wherein the compound is selected from the group consisting of:

2-(2-{[(2-Aminobenzyl)sulfonyl]amino}ethyl)-4-{2-[1-benzhydryl-5-chloro-1H-indol-3-yl]ethoxy}benzoic acid;

4-{2-[1-Benzhydryl-5-chloro-2-(2-{[(dimethylamino)sulfonyl]amino}ethyl)-1H-indol-3-yl]ethoxy}benzoic acid;

4-{2-[1-Benzhydryl-5-chloro-2-(2-{[(3,4-difluorobenzyl)sulfonyl]amino}-ethyl)-1H-indol-3-yl]ethoxy}benzoic acid;

4-{2-[1-benzhydryl-5-chloro-2-(2-{[(2-naphthylmethyl)sulfonyl]amino}ethyl)-1H-indol-3-yl]ethoxy}benzoic acid; and

3-({[(2-{1-benzhydryl-3-[2-(4-carboxyphenoxy)ethyl]-5-chloro-1H-indol-2-yl}ethyl)amino]sulfonyl}methyl)benzoic acid;

and a pharmaceutically acceptable salt form thereof.

21. A method of claim 1 wherein the compound is selected from the group consisting of:

4-(2-{1-benzhydryl-5-chloro-2-[2-({[(E)-2-phenylethenyl]sulfonyl}amino)ethyl′1H-indol-3-yl}ethoxy)benzoic acid;

4-{2-[1-benzhydryl-5-chloro-2-(2-{[(trifluoromethyl)sulfonyl)amino}ethyl)-1H-indol-3-yl]ethoxy}benzoic acid;

4-[2-(1-benzhydryl-5-chloro-2-{2-[(cyclopropylsulfonyl)amino]ethyl}-1H-indol-3-yl)ethoxy]benzoic acid;

4-(2-{1-benzhydryl-2-[2-({[3,5-bis(trifluoromethyl)benzyl]sulfonyl}amino)ethyl]-5-chloro-1H-indol-3-yl}ethoxy)benzoic acid; and

2-{[(2-{1-benzhydryl-3-[2-(4-carboxyphenoxy)ethyl]-5-chloro-1H-indol-2-yl}ethyl)amino]sulfonyl}benzoic acid;

and a pharmaceutically acceptable salt form thereof.

22. A method of claim 1 wherein the compound is selected from the group consisting of:

4-[2-(1-benzhydryl-5-chloro-242-[(2-naphthylsulfonyl)amino]ethyl}-1H-indol-3-yl)ethoxy]benzoic acid;

4-{2-[1-benzhydryl-5-chloro-2-(2-{[(3,5-dichlorophenyl)sulfonyl]amino}ethyl)-1H-indol-3-yl]ethoxy}benzoic acid;

4-{2-[1-benzhydryl-5-chloro-2-(2-{[(3,4-dichlorophenyl)sulfonyl]amino}ethyl)-1H-indol-3-yl]ethoxy}benzoic acid;

4-{2-[1-benzhydryl-5-chloro-2-(2-{[(2,3-dichlorobenzyl)sulfonyl]amino}ethyl)-1H-indol-3-yl]ethoxy}benzoic acid; and

4-{2-[1-benzhydryl-5-chloro-2-(2-{[(2,4-dichlorobenzyl)sulfonyl]amino}ethyl)-1H-indol-3-yl]ethoxy}benzoic acid;

and a pharmaceutically acceptable salt form thereof.

23. A method of claim 1 wherein the compound is selected from the group consisting of:

4-{2-[1-benzhydryl-5-chloro-2-(2-{[(2,4-dichlorobenzyl)sulfonyl]amino}ethyl)-1H-indol-3-yl]ethoxy}benzoic acid;

4-{2-[1-benzhydryl-5-chloro-2-(2-{[(4-chloro-2-nitrobenzyl)sulfonyl]amino}ethyl)-1H-indol-3-yl]ethoxy}benzoic acid;

4-[2-(1-benzhydryl-2-{2-[(benzylsulfonyl)amino]ethyl}-5-morpholin-4-yl-1H-indol-′3-yl)ethoxy]benzoic acid;

4-{2-[1-Benzhydryl-5-chloro-2-(2-{[(2-cyanobenzyl)sulfonyl]amino}ethyl)-1H-indol-3-yl]ethoxy}benzoic acid; and

4-{2-[1-Benzhydryl-5-chloro-2-(2-{[(2-cyanobenzyl)sulfonyl]amino}ethyl)-1H-indol-3-yl]ethoxy}benzoic acid;

and a pharmaceutically acceptable salt form thereof.

24. A method of claim 1 wherein the compound is selected from the group consisting of:

4-{2-[1-Benzhydryl-5-chloro-2-(2-{[(3-cyanobenzyl)sulfonyl]amino}ethyl)-1H-indol-3-yl]ethoxy}benzoic acid;

4-{2-[1-Benzhydryl-5-chloro-2-(2-{[(4-cyanobenzyl)sulfonyl]amino}ethyl)-1H-indol-3-yl]ethoxy}benzoic acid;

4-(2-{1-Benzhydryl-5-chloro-2-[2-({[4-(1piperidinylsulfonyl)benzyl]sulfonyl}amino)ethyl]-1H-indol-3-yl}ethoxy)benzoic acid;

4-(2-{2-[2-({[4-(Aminosulfonyl)benzyl]sulfonyl}amino)ethyl]-1-benzhydryl-5-chloro-1H-indol-3-yl}ethoxy)benzoic acid; and

4-(2-{1-Benzhydryl-5-chloro-2-[2-(4-methanesulfonyl-phenylmethanesulfonylamino)-ethyl]-1H-indol-3-yl}-ethoxy)-benzoic acid;

and a pharmaceutically acceptable salt form thereof.

25. A method of claim 1 wherein the compound is selected from the group consisting of:

4-(2-{1-Benzhydryl-5-chloro-2-[2-(4-diethylsulfamoyl-phenylmethanesulfonylamino)-ethyl]-1H-indol-3-yl}-ethoxy)-benzoic acid;

4-{3-[1-Benzhydryl-5-chloro-2-(2-phenylmethanesulfonylamino-ethyl)-1H-indol-3-yl]-propyl}-benzoic acid;

4-{3-[1-benzhydryl-5-chloro-2-(2-{[(3,5-dichlorobenzyl)sulfonyl]amino}ethyl)-1H-indol-3-yl]propyl}benzoic acid;

4-{3-[1-benzhydryl-5-chloro-2-(2-{[(3,4-dichlorobenzyl)sulfonyl]amino}ethyl)-1H-indol-3-yl]propyl}benzoic acid;

4-[2-(1-benzhydryl-5-chloro-2-(2-[(methylsulfonyl)amino]ethyl)-1H-indol-3-yl]ethoxy}benzoic acid;

and a pharmaceutically acceptable salt form thereof.

26. A method of claim 1 wherein the compound is selected from the group consisting of:

4-[2-(1-benzhydryl-5-chloro-2-{2-[(phenylsulfonyl)amino]ethyl}-1H-indol-3-yl]ethoxy}benzoic acid;

4-(2-{1-benzhydryl-5-chloro-2-[2-({[3-(trifluoromethyl)benzyl]sulfonyl}amino)ethyl]-1H-indol-3-yl}ethoxy)benzoic acid;

2-{((2-{([(2-{1-benzhydryl-3-[2-(4-carboxyphenoxy)ethyl]-5-chloro-1H-indol-2-yl}ethyl)amino]sulfonyl}ethyl)amino]carbonyl}benzoic acid;

4-{2-[{1-benzhydryl-5-chloro-2-(2-{[(3-(pyridinylmethyl)sulfonyl]amino}ethyl)-1H-indol-3-yl]ethoxy}benzoic acid; and

4-{2-[{1-benzhydryl-5-chloro-2-(2-{[(4-(pyridinylmethyl)sulfonyl]amino}ethyl)-1H-indol-3-yl]ethoxy}benzoic acid;

and a pharmaceutically acceptable salt form thereof.

27. A method of claim 1 wherein the compound is selected from the group consisting of:

4-{2-[{1-benzhydryl-5-chloro-2-(2-{[(2-(pyridinylmethyl)sulfonyl]amino}ethyl)-1H-indol-3-yl]ethoxy}benzoic acid;

4-{3-[1-benzhydryl-5-chloro-2-(2-{[(2,6-dimethylbenzyl)sulfonyl]amino}ethyl)-1H-indoly-3-yl]propyl}benzoic acid;

4-{2-[1-benzhydryl-5-chloro-2-(2-{[(cyclohexylmethyl)sulfonyl]amino}ethyl)-1H-indol-3-yl]ethoxy}benzoic acid;

4-{2-[1-benzhydryl-5-chloro-2-(2-{[(4-nitrobenzyl)sulfonyl]amino}ethyl)-1H-indol-3-yl]ethoxy}benzoic acid; and

4-{2-[1-benzhydryl-5-chloro-2-(2-{[(3-nitrobenzyl)sulfonyl]amino}ethyl)-1H-indol-3-yl]ethoxy}benzoic acid;

and a pharmaceutically acceptable salt form thereof.

28. A method of claim 1 wherein the compound is selected from the group consisting of:

4-{2-[1-Benzhydryl-5-chloro-2-{2-[({2-nitrobenzyl}-sulfonyl)amino]ethyl}-1H-indol-3-yl) propyl]benzoic acid;

4-{3-[1-benzhydryl-5-chloro-2-(2-{[(4-fluorobenzyl)sulfonyl]amino}ethyl)-1H-indol-3-yl]propyl}benzoic acid;

4-(3-{1-benzhydryl-5-chloro-2-[2-({[4-(trifluoromethyl)benzyl]sulfonylamino)ethyl]-1H-indol-3-yl}propyl)benzoic acid;

4-(3-{1-benzhydryl-5-chloro-2-[2-({[3-(trifluoromethyl)benzyl]sulfonyl}amino)ethyl]-1H-indol-3-yl}propyl)benzoic acid; and

4-{3-[1-benzhydryl-5-chloro-2-(2-{[(4-chlorobenzyl)sulfonyl]amino}ethyl)-1H-indol-3-yl]propyl}benzoic acid;

and a pharmaceutically acceptable salt form thereof.

29. A method of claim 1 wherein the compound is selected from the group consisting of:

4-{3-[1-benzhydryl-5-chloro-2-(2-{[(2-pyridinylmethyl)sulfonyl]amino}ethyl)-1H-indol-3-yl]propyl}benzoic acid;

4-{3-[1-benzhydryl-5-chloro-2-(2-{[(3-pyridinylmethyl)sulfonyl]amino}ethyl)-1H-indol-3-yl]propyl}benzoic acid;

4-{3-[1-benzhydryl-5-chloro-2-(2-{[(4-pyridinylmethyl)sulfonyl]amino}ethyl)-1H-indol-3-yl]propyl}benzoic acid;

4-{3-[1-benzhydryl-5-chloro-2-(2-{[(2-chlorobenzyl)sulfonyl]amino}ethyl)-1H-indol-3-yl]propyl)benzoic acid; and

4-{3-[1-benzhydryl-5-chloro-2-(2-{[(3-nitrobenzyl)sulfonyl]amino}ethyl)-1H-indol-3-yl]propyl}benzoic acid;

and a pharmaceutically acceptable salt form thereof.

30. A method of claim 1 wherein the compound is selected from the group consisting of:

4-(3-(1-benzhydryl-5-chloro-2-(2-{[(3-chlorobenzyl)sulfonyl]amino}ethyl)-1H-indol-3-yl]propyl}benzoic acid;

4-{3-[1-benzhydryl-5-chloro-2-(2-{[(2,5-dichlorobenzyl)sulfonyl]amino}ethyl)-1H-indol-3-yl]propyl}benzoic acid;

4-{3-[1-benzhydryl-5-chloro-2-(2-{[(3-methoxybenzyl)sulfonyl]amino}ethyl)-1H-indol-3-yl]propyl}benzoic acid;

4-{3-[2-(2-{[(2-aminobenzyl)sulfonyl]amino}ethyl)-1-benzhydryl-5-chloro-1H-indol-3-yl]propyl}benzoic acid; and

4-{3-[1-Benzhydryl-5-chloro-2-(2-{[(2-methylbenzyl)sulfonyl]amino}ethyl)-1H-indol-3-yl]propyl}benzoic acid;

and a pharmaceutically acceptable salt form thereof.

31. A method of claim 1 wherein the compound is selected from the group consisting of:

4-{2-[1-Benzhydryl-5-chloro-2-(2-{[(4-trifluorometoxybenzyl)sulfonyl]amino}ethyl)-1H-indol-3-yl]ethoxy}benzoic acid;

4-{2-[1-Benzhydryl-5-chloro-2-(2-{[(2-fluoro-6-nitrobenzyl)sulfonyl]amino}ethyl)-1H-indol-3-yl]ethoxy}benzoic acid;

4-{2-[1-Benzhydryl-5-chloro-2-(2-{[(2-dichlorobenzyl)sulfonyl]amino}ethyl)-1H-indol-3-yl]ethoxy}benzoic acid;

4-{2-[1-Benzhydryl-5-chloro-2-(2-{[(2,6-difluorobenzyl)sulfonyl]amino}ethyl)-1H-indol-3-yl]ethoxy}benzoic acid; and

4-(2-{1-benzhydryl-5-chloro-2-[2-({[(6-chloro-3-pyridinyl)methyl]sulfonyl}amino)ethyl]-1H-indol-3-yl}ethoxy)benzoic acid;

and a pharmaceutically acceptable salt form thereof.

32. A method of claim 1 wherein the compound is selected from the group consisting of:

4-(2-{1-benzhydryl-5-chloro-2-[2-({[(5,6-dichloro-2-[pyridinyl)methyl]sulfonylamino)ethyl]-1H-indol-3-yl}ethoxy)benzoic acid;

4-{2-[1-Benzhydryl-5-chloro-2-(2-{[(3-methoxybenzyl)sulfonyl]amino}ethyl)-1H-indol-3-yl]ethoxy}benzoic acid;

4-{2-[1-Benzhydryl-5-chloro-2-(2-{[(3,5-dimethylbenzyl)sulfonyl]amino}ethyl)-1H-indol-3-yl]ethoxy}benzoic acid;

4-{2-[1-Benzhydryl-5-chloro-2-(2-{[(2-methylbenzyl)sulfonyl]amino}ethyl)-1H-indol-3-yl]ethoxy}benzoic acid; and

4-{2-[1-Benzhydryl-5-chloro-2-(2-{[(2,6-dichlorobenzyl)sulfonyl]amino}ethyl)-1H-indol-3-yl]ethoxy}benzoic acid;

and a pharmaceutically acceptable salt form thereof.

33. A method of claim 1 wherein the compound is selected from the group consisting of:

4-(2-{1-benzhydryl-5-chloro2[2({[(phenylsulfanyl)methyl]sulfonyl}amino)ethyl]-1H-indol-3-yl}ethoxy)benzoic acid;

4-(2-{1-benzhydryl-5-chloro-2-[2-(2,6-dimethyl-phenylsulfanylmethanesulfonylamino)-ethyl]-]-1H-indol-3-yl}-ethoxy)-benzoic acid;

4-(2-{1-benzhydryl-5-chloro-2-[2-(2-methoxy-phenylsulfanylmethanesulfonylamino)-ethyl]-]-1H-indol-3-yl}-ethoxy)-benzoic acid;

4-(2-{1-benzhydryl-5-chloro-2-[2-(2-chloro-6-methyl-phenylsulfanylmethanesulfonylamino)-ethyl]-]-1H-indol-3-yl}-ethoxy)-benzoic acid; and

4-(2-{1-benzhydryl-5-chloro-2-[2-(3,5-dichloro-phenylsulfanylmethanesulfonylamino)-ethyl]-]-1H-indol-3-yl}-ethoxy)-benzoic acid;

and a pharmaceutically acceptable salt form thereof.

34. A method of claim 1 wherein the compound is selected from the group consisting of:

4-(2-{1-benzhydryl-5-chloro-2-[2-(3,4-dimethoxy-phenylsulfanylmethanesulfonylamino)-ethyl]-]-1H-indol-3-yl}-ethoxy)-benzoic acid;

4-(2-{1-Benzhydryl-5-chloro-2-[2-(2-morpholin-4-ylethanesulfonylamino)-ethyl]-1H-indol-3-yl}-ethoxy)-benzoic acid;

4-(2-{1-Benzhydryl-5-chloro-2-[2-(2-pyrazol-1-yl-ethanesulfonylamino)-ethyl]-1H-indol-3-yl}-ethoxy)-benzoic acid;

4-(2-{1-Benzhydryl-5-chloro-2-[2-(2-phenylamino-ethanesulfonylamino)-ethyl]-1H-indol-3-yl}-ethoxy)-benzoic acid; and

4-(2-{1-benzhydryl-5-chloro-2-[2-({[2-(1,4-dioxa-8-azaspiro[4.5]dec-8-yl)ethyl]sulfonyl}amino)ethyl]-1H-indol-3-yl}ethoxy)benzoic acid;

and a pharmaceutically acceptable salt form thereof.

35. A method of claim 1 wherein the compound is selected from the group consisting of:

4-[2-(1-benzhydryl-5-chloro-2-{2-[({2-[4-(2-pyridinyl)-1-piperazinyl]ethyl}sulfonyl)amino]ethyl}-1H-indol-3-yl)ethoxy]benzoic acid;

4-(2-{1-benzhydryl-5-chloro-2-[2-({[2-(1H-1,2,4-triazol-1-yl)ethyl]sulfonyl}amino)ethyl]-1H-indol-3-yl}ethoxy)benzoic acid;

4-(2-{1-benzhydryl-5-chloro-2-[2-({[2-(3,5-dimethyl-1H-pyrazol-1-yl)ethyl]sulfonyl}amino)ethyl]-1H-indol-3-yl}ethoxy)benzoic acid;

4-(2-{1-benzhydryl-5-chloro-2-[2-({[2-(3-methyl-1H-pyrazol-1-yl)ethyl]sulfonyl}amino)ethyl]-1H-indol-3-yl}ethoxy)benzoic acid; and

4-(2-{1-benzhydryl-5-chloro-2-[2-({[2-(4-methyl-1H-pyrazol-1-yl)ethyl]sulfonyl}amino)ethyl]-1H-indol-3-yl}ethoxy)benzoic acid;

and a pharmaceutically acceptable salt form thereof.

36. A method of claim 1 wherein the compound is selected from the group consisting of:

4-[2-(1-benzhydryl-5-chloro-2-{2-[({2-[(2R,6S)-2,6-dimethyl-1-piperidinyl]ethyl}sulfonyl)amino]ethyl}-1H-indol-3-yl)ethoxy]benzoic acid;

4-(2-{1-benzhydryl-5-chloro-2-[2-({[2-(2-thioxo-1-imidazolidinyl)ethyl]sulfonyl}amino)ethyl]-1H-indol-3-yl}ethoxy)benzoic acid;

4-(2-{1-benzhydryl-5-chloro-2-[2-({[2-(1,3-thiazolidin-3-yl)ethyl]sulfonyl}amino)ethyl]-1H-indol-3-yl}ethoxy)benzoic acid;

4-(2-{1-benzhydryl-5-chloro-2-[2-(2-[1,2,3]triazol-1-yl-ethanesulfonylamino)-ethyl]-1H-indol-3-yl}ethoxy)benzoic acid; and

4-(3-{1-Benzhydryl-5-chloro-2-[2-(2-morpholin-4-yl-ethanesulfonylamino)-ethyl]-1H-indol-3-yl}-propyl)-benzoic acid;

and a pharmaceutically acceptable salt form thereof.

37. A method of claim 1 wherein the compound is selected from the group consisting of:

4-[3-(1-Benzhydryl-5-chloro-2-{2-[2-(2,6-dimethyl-piperidin-1-yl)-ethanesulfonylamino]-ethyl)-1H-indol-3-yl)-propyl]-benzoic acid;

4-[3-(1-Benzhydryl-5-chloro-2-{2-[2-(3,5-dimethyl-pyrazol-1-yl)-ethanesulfonylamino]-ethyl}-1H-indol-3-yl)-propyl]-benzoic acid;

4-(2-{1-benzhydryl-5-chloro-2-[2-(2-tetrazol-2-yl-ethanesulfonylamino)-ethyl]-1H-indol-3-yl}ethoxy)benzoic acid;

4-(2-{1-benzhydryl-5-chloro-2-[2-(2-tetrazol-1-yl-ethanesulfonylamino)-ethyl]-1H-indol-3-yl}ethoxy)benzoic acid; and

4-{2-[1-Benzhydryl-6-chloro-2-(2-phenylmethanesulfonylamino-ethyl)-1H-indol-3-yl]-ethoxy}-benzoic acid;

and a pharmaceutically acceptable salt form thereof.

38. A method of claim 1 wherein the compound is selected from the group consisting of:

4-(2-{1-Benzhydryl-6-chloro-2-[2-(3,4-dichloro-phenylmethanesulfonylamino)-ethyl]-1H-indol-3-yl}-ethoxy)-benzoic acid;

4-(2-{1-Benzhydryl-6-chloro-2-[2-(3,5-dichloro-phenylmethanesulfonylamino)-ethyl]-1H-indol-3-yl}-ethoxy)-benzoic acid;

4-{2-[1-Benzhydryl-5-chloro-2-(2-{[(2-cyanobenzyl)sulfonyl]amino}ethyl)-1H-indol-3-yl]ethoxy}benzoic acid;

4-{2-[1-Benzhydryl-5-chloro-2-(2-{[(tetrahydro-2H-pyran-2-ylmethyl)sulfonyl]amino}ethyl)-1H-indol-3-yl]ethoxy}benzoic acid; and

4-{2-[1-Benzhydryl-2-(2-{f[(1,3-benzoxazol-2-ylmethyl)sulfonyl]amino}ethyl)-5-chloro-1H-indol-3-yl]ethoxy}benzoic acid;

and a pharmaceutically acceptable salt form thereof.

39. A method of claim 1 wherein the compound is selected from the group consisting of:

4-{2-[1-Benzhydryl-5-chloro-2-(2-{[(cyanomethyl)sulfonyl]amino}ethyl)-1H-indol-3-yl]ethoxy}benzoic acid;

4-{2-[1-Benzhydryl-5-chloro-2-(2-{[(3-thienylmethyl)sulfonyl]amino}ethyl)-1H-indol-3-yl]ethoxy}benzoic acid;

4-[2-(1-Benzhydryl-5-chloro-2-{2-[2-(2-methyl-pyrrolidin-1-yl)-ethanesulfonylamino]-ethyl}-1H-indol-3-yl)-ethoxy]-benzoic acid;

4-[2-(1-Benzhydryl-5-chloro-2-{2-[2-(2-methyl-piperidin-1-yl)-ethanesulfonylamino]-ethyl}-1H-indol-3-yl)-ethoxy]-benzoic acid; and

4-[2-(1-Benzhydryl-5-chloro-2-{2-[2-(2,5-dimethyl-pyrrolidin-1-yl)-ethanesulfonylamino]-ethyl}-1H-indol-3-yl)-ethoxy]-benzoic acid;

and a pharmaceutically acceptable salt form thereof.

40. A method of claim 1 wherein the compound is selected from the group consisting of:

4-(2-{1-Benzhydryl-5-chloro-2-[2-(2-thiomorpholin-4-yl-ethanesulfonylamino)-ethyl]-1H-indol-3-yl}-ethoxy)-benzoic acid;

4-(2-{1-Benzhydryl-5-chloro-2-[2-(2-piperidin-1-yl-ethanesulfonylamino)-ethyl]-1H-indol-3-yl}-ethoxy)-benzoic acid;

4-{2-[1-benzhydryl-5-chloro-2-(2-o-tolylsulfanylmethanesulfonylamino-ethyl)-1H-indol-3-yl]-ethoxy)-benzoic acid;

4-(2-{1-benzhydryl-5-chloro-2-[2-(2-chloro-phenylsulfanylmethane-sulfonylamino)-ethyl]-1H-indol-3-yl}-ethoxy)-benzoic acid; or

4-(2-{1-benzhydryl-5-chloro-2-[2-(2,6-dichloro-phenylsulfanylmethane-sulfonylamino)-ethyl]-1H-indol-3-yl}-ethoxy)-benzoic acid;

and a pharmaceutically acceptable salt form thereof.

41. A method of claim 1 wherein the compound is selected from the group consisting of:

4-(2-{1-benzhydryl-5-chloro-2-[2-(2,5-dimethoxy-phenylsulfanylmethanesulfonylamino)-ethyl]-1H-indol-3-yl)-ethoxy)-benzoic acid;

4-[2-(1-benzhydryl-5-chloro-2-{2-[2-(3-hydroxy-pyrrolidine-1-yl)-ethanesulfonylamino]-ethyl}-1H-indol-3-yl)-ethoxy]-benzoic acid;

4-[2-(1-Benzhydryl-5-chloro-2-{2-[2-(4-hydroxy-piperidin-1-yl)-ethanesulfonylamino]-ethyl}-1H-indol-3-yl)-ethoxy]-benzoic acid;

4-(2-{1-Benzhydryl-5-chloro-2-[2-(2-pyrrolidin-1-yl-ethanesulfonylamino)-ethyl]-1H-indol-3-yl}-ethoxy)-benzoic acid; and

4-[2-(1-Benzhydryl-5-chloro-2-{2-[2-(2-dimethylaminomethyl-piperidin-1-yl)-ethanesulfonylamino]-ethyl}-1H-indol-3-yl)-ethoxy]-benzoic acid;

and a pharmaceutically acceptable salt form thereof.

42. A method of claim 1 wherein the compound is selected from the group consisting of:

4-(2-{1-Benzhydryl-5-chloro-2-[2-(2-imidazol-1-yl-ethanesulfonylamino)-ethyl]-1H-indol-3-yl}-ethoxy)-benzoic acid;

4-{3-[1-benzhydryl-5-chloro-2-(2-{[(2,6-difluorobenzyl)sulfonyl]amino}ethyl)-1H-indol-3-yl]propyl}benzoic acid;

4-{3-[1-benzhydryl-2-(2-{[(3,4-dichlorobenzyl)sulfonyl]amino}ethyl)-1H-indol-3-yl]propyl}benzoic acid;

3-[4-({2-[1-Benzhydryl-5-chloro-2-(2-{[(2-chlorobenzyl)sulfonyl]amino}ethyl)-1H-indol-3-yl]ethyl}sulfonyl)phenyl]propanoic acid; and

3-(4-{[2-(1-Benzhydryl-2-{2-[(benzylsulfonyl)amino]ethyl}-5-chloro-1H-indol-3-yl)ethyl]sulfonyl}phenyl)propanoic acid;

and a pharmaceutically acceptable salt form thereof.

43. A method of claim 1 wherein the compound is selected from the group consisting of:

3-[4-({2-[1-benzhydryl-5-chloro-2-(2-{[(2,6-difluorobenzyl)sulfonyl]amino}ethyl)-1H-indol-3-yl]ethyl}sulfonyl)phenyl]propanoic acid;

3-[4-({2-[1-benzhydryl-5-chloro-2-(2-{[(2-fluorobenzyl)sulfonyl]amino}ethyl)-1H-indol-3-yl]ethyl}sulfonyl)phenyl]propanoic acid;

3-[4-({2-[1-benzhydryl-5-chloro-2-(2-{[(2-chlorobenzyl)sulfonyl]amino}ethyl)-1H-indol-3-yl]ethyl}sulfonyl)phenyl]propanoic acid;

4-({[(1-benzhydryl-2-{2-[(benzylsulfonyl)amino]ethyl}-5-chloro-1H-indol-3-yl)methyl]amino}methyl)benzoic acid; and

4-{[2-(1-benzhydryl-2-{2-[(benzylsulfonyl)amino]ethyl}-5-chloro-1H-indol-3yl)ethyl]sulfonyl}benzoic acid;

and a pharmaceutically acceptable salt form thereof.

44. A method of claim 1 wherein the compound is selected from the group consisting of:

4-({2-[1-benzhydryl-5-chloro-2-(2-{[(2-chlorobenzyl)sulfonyl]amino}ethyl)-1H-indol-3-yl]ethyl}sulfonyl)benzoic acid;

4-({2-[1-benzhydryl-5-chloro-2-(2-{[(2,6-difluorobenzyl)sulfonyl]amino}ethyl)-1H-indol-3-yl]ethyl}sulfonyl)benzoic acid;

4-({2-[1-benzhydryl-5-chloro-2-(2-{[(2-fluorobenzyl)sulfonyl]amino}ethyl)-1H-indol-3-yl]ethyl}sulfonyl)benzoic acid; and

4-(2-{1-Benzhydryl-5-chloro-2-[2-(2-pyrrolidin-1-yl-ethanesulfonylamino)-ethyl]-1H-indol-3-yl}-ethoxy)-benzoic acid;

and a pharmaceutically acceptable salt form thereof.

45. A method of claim 1 wherein the compound is selected from the group consisting of:

4-((2-[1-benzhydryl-5-chloro-2-(2-{[(3,4-dichlorobenzyl)sulfonyl]amino}ethyl)1H-indol-3-yl]ethyl}sulfonyl)benzoic acid;

4-({2-[1-benzhydryl-5-chloro-2-(2-{[(2,6-dimethylbenzyl)sulfonyl]amino}ethyl)1H-indol-3-yl]ethyl}sulfonyl)benzoic acid; and

4-[2-(1-benzhydryl-2-{3-[(benzylsulfonyl)amino]propyl}-5-chloro-1H-indol-3-yl)ethoxy]benzoic acid;

and a pharmaceutically acceptable salt form thereof.

46. A method of claim 1 wherein the disorder is rheumatoid arthritis.

47. A method of claim 1 wherein the disorder is osteoarthritis.

48. A method of claim 1 wherein the disorder is juvenile arthritis.