Indazoles as glucocorticoid receptor ligands

1. A compound of formula (I):

wherein

A 1 represents 5-fluoro-2-methoxy-phenyl or 5-fluoro-2-hydroxy-phenyl;

X represents —C(R 3 )—;

when X represents —C(R 3 )—, R 2 represents hydrogen and R 1 represents fluorine, R 3 represents hydrogen or fluorine,

when X represents —C(R 3 )— and R 2 and R 1 each represent hydrogen, R 3 represents hydrogen, hydroxy, methoxy or fluorine,

when X represents —C(R 3 )— and R 2 represents hydroxy, methoxy, —CO 2 CH 3 or —CO 2 CH 2 CH 3 , R 1 and R 3 each represent hydrogen; and

Y represents H or methyl;

or salts thereof.

2. A compound according to claim 1 wherein A 1 represents 5-fluoro-2-hydroxy-phenyl.

3. A compound according to claim 1 wherein A 1 represents 5-fluoro-2-methoxy-phenyl.

4. A compound according to claim 1 wherein X represents —C(R 3 )—, R 2 represents hydrogen, R 1 represents fluorine and R 3 represents hydrogen or fluorine.

5. A compound according to claim 4 wherein R 3 represents fluorine.

6. A compound according to claim 1 wherein X represents —C(R 3 )—, R 2 and R 1 each represent hydrogen and R 3 represents hydrogen, hydroxy, methoxy or fluorine.

7. A compound according to claim 1 wherein X represents —C(R 3 )—, R 2 represents hydroxy, methoxy, —CO 2 CH 3 or —CO 2 CH 2 CH 3 , and R 1 and R 3 each represent hydrogen.

8. A compound according to claim 1 wherein Y represents methyl.

9. A compound which is selected from the group consisting of:

2-({[1-(2,4-difluorophenyl)-1H-indazol-4-yl]amino}methyl)-1,1,1-trifluoro-4-[5-fluoro-2-(methyloxy)phenyl]-4-methyl-2-pentanol which showed a retention time of 5.19 min on analytical chiral HPLC (25×0.46 cm Chiralcel OD column, heptane:EtOH 7:3, eluting at 1 ml/min);

1,1,1-trifluoro-4-[5-fluoro-2-(methyloxy)phenyl]-4-methyl-2-{[(6-methyl-1-phenyl-1H-indazol-4-yl)amino]methyl}-2-pentanol which showed a retention time of 6.64 min on analytical chiral HPLC (25×0.46 cm Chiralcel OD-H column, heptane:EtOH 4:1 eluting at 1 mL/min);

(2R) 2-({[1-(2,4-difluorophenyl)-6-methyl-1H-indazol-4-yl]amino}methyl)-1,1,1-trifluoro-4-[5-fluoro-2-(methyloxy)phenyl]-4-methyl-2-pentanol;

4-(2,3-dihydro-1-benzofuran-7-yl)-1,1,1-trifluoro-4-methyl-2-{[(6-methyl-1-phenyl-1H-indazol-4-yl)amino]methyl}-2-pentanol;

(2R) 4-(2,3-dihydro-1-benzofuran-7-yl)-1,1,1-trifluoro-4-methyl-2-{[(6-methyl-1-phenyl-1H-indazol-4-yl)amino]methyl}-2-pentanol;

4-(4-{[4-[5-fluoro-2-(methyloxy)phenyl]-2-hydroxy-4-methyl-2-(trifluoromethyl)pentyl]amino}-6-methyl-1H-indazol-1-yl)phenol;

4-fluoro-2-[4,4,4-trifluoro-3-hydroxy-3-({[1-(4-hydroxyphenyl)-6-methyl-1H-indazol-4-yl]amino}methyl)-1,1-dimethylbutyl]phenol;

4-fluoro-2-[4,4,4-trifluoro-3-hydroxy-3-({[1-(3-hydroxyphenyl)-6-methyl-1H-indazol-4-yl]amino}methyl)-1,1-dimethylbutyl]phenol;

4-fluoro-2-[4,4,4-trifluoro-3-hydroxy-3-({[1-(3-hydroxyphenyl)-6-methyl-1H-indazol-4-yl]amino}methyl)-1,1-dimethylbutyl]phenol which showed a retention time of 13.77 min on analytical chiral HPLC (25×0.46 cm Chiralpak AD column, heptane:EtOH 3:1 eluting at 1 mL/min);

1,1,1-trifluoro-4-[5-fluoro-2-(methyloxy)phenyl]-2-({[1-(2-fluorophenyl)-6-methyl-1H-indazol-4-yl]amino}methyl)-4-methyl-2-pentanol, which showed a retention time of 7.4 min on analytical chiral HPLC (25×0.46 cm Chiralcel OJ column, heptane:EtOH 7:3 eluting at 1 mL/min);

1,1,1-trifluoro-4-[5-fluoro-2-(methyloxy)phenyl]-2-({[1-(4-fluorophenyl)-6-methyl-1H-indazol-4-yl]amino}methyl)-4-methyl-2-pentanol, which showed a retention time of 6.8 min on analytical chiral HPLC (25×0.46 cm Chiralcel OD column, heptane:EtOH 85:15 eluting at 1 mL/min);

and salts thereof.

10. A pharmaceutical composition comprising a compound as claimed in claim 1 , in admixture with one or more physiologically acceptable diluents or carriers.

11. A pharmaceutical aerosol formulation comprising a compound as claimed in claim 1 and a fluorocarbon or hydrogen-containing chlorofluorocarbon or mixtures thereof as propellant, optionally in combination with a surfactant and/or a cosolvent.

12. A pharmaceutical aerosol formulation as claimed in claim 11 wherein the propellant is selected from the group consisting of 1,1,1,2-tetrafluoroethane, 1,1,1,2,3,3,3-heptafluoro-n-propane and mixtures thereof.