Phenyl and benzodioxinyl substituted indazoles derivatives

1. A compound of formula Ib:

wherein:

A is C 1-4 alkyl, C 1-4 alkoxy or C 1-4 haloalkyl;

R 3 is C 5-10 heteroaryl;

W is phenyl substituted by —C(O)NR 7 R 8 ;

R 7 is hydrogen or C 1-4 alkyl;

R 8 is selected from hydrogen,

C 1-6 alkyl (optionally substituted by one or two groups selected from hydroxyl, C 5-10 aryl and C 5-10 heteroaryl),

C 3-7 cycloalkyl (optionally substituted by hydroxyl), and

C 5-10 heterocyclyl (optionally substituted by one or two groups selected from hydroxyl and oxo);

or a pharmaceutically acceptable salt thereof.

2. The compound according to claim 1 , wherein:

A is C 1-2 haloalkyl;

R 3 is C 5-10 heteroaryl;

W is phenyl substituted by —C(O)NR 7 R 8 ;

R 7 is hydrogen;

R 8 is selected from C 1-4 alkyl (optionally substituted by hydroxyl, C 5-6 aryl and C 5-6 heteroaryl),

C 5-6 cycloalkyl (optionally substituted by hydroxyl), and

C 5-6 heterocyclyl (optionally substituted by oxo);

or a pharmaceutically acceptable salt thereof.

3. The compound according to claim 1 , wherein A is fluoromethyl, difluoromethyl, trifluoromethyl, fluoroethyl, difluoroethyl, trifluoroethyl, fluoropropyl, difluoropropyl or trifluoropropyl.

4. The compound according to claim 1 , wherein R 8 is selected from any one of dioxidotetrahydrothiophen-3-yl, oxidotetrahydrothiophen-3-yl, tetrahydrofuran-3-yl, oxotetrahydrofuran-3-yl, cyclopentyl, hydroxycyclopentyl, hydroxybutyl, pyridin-4-ylmethyl, pyridin-3-ylmethyl, or phenylmethyl.

5. The compound according to claim 1 , wherein said compound is selected from the group of:

3-(5-{[(1R,2S)-2-[(2,2-difluoropropanoyl)amino]-1-(2,3-dihydro-1,4-benzodioxin-6-yl)propyl]oxy}-1H-indazol-1-yl)-N-[(3S)-1,1-dioxidotetrahydrothiophen-3-yl]benzamide (E1),

3-(5-{[(1R,2S)-2-[(2,2-difluoropropanoyl)amino]-1-(2,3-dihydro-1,4-benzodioxin-6-yl)propyl]oxy}-1H-indazol-1-yl)-N-[(3R)-1,1-dioxidotetrahydrothiophen-3-yl]benzamide,

3-(5-{[(1R,2S)-2-[(2,2-difluoropropanoyl)amino]-1-(2,3-dihydro-1,4-benzodioxin-6-yl)propyl]oxy}-1H-indazol-1-yl)-N-[(3RS)-1,1-dioxidotetrahydrothiophen-3-yl]benzamide,

3-(5-{[2-[(2,2-difluoropropanoyl)amino]-1-(2,3-dihydro-1,4-benzodioxin-6-yl)propyl]oxy}-1H-indazol-1-yl)-N-[1,1-dioxidotetrahydrothiophen-3-yl]benzamide,

3-[5-({(1R,2S)-1-(4H-1,3-Benzodioxin-7-yl)-2-[(2,2-difluoropropanoyl)amino]propyl}oxy)-1H-indazol-1-yl]-N-[(3R)-1,1-dioxidotetrahydrothiophen-3-yl]benzamide,

3-[5-({(1R,2S)-1-(4H-1,3-benzodioxin-7-yl)-2-[(2,2-difluoropropanoyl)amino]propyl}oxy)-1H-indazol-1-yl]-N-[(3S)-1,1-dioxidotetrahydrothiophen-3-yl]benzamide,

3-[5-({(1R,2S)-1-(4H-1,3-benzodioxin-7-yl)-2-[(2,2-difluoropropanoyl)amino]propyl}oxy)-1H-indazol-1-yl]-N-[(3RS)-1,1-dioxidotetrahydrothiophen-3-yl]benzamide,

3-[5-({1-(4H-1,3-benzodioxin-7-yl)-2-[(2,2-difluoropropanoyl)amino]propyl}oxy)-1H-indazol-1-yl]-N-[1,1-dioxidotetrahydrothiophen-3-yl]benzamide,

3-(5-{[(1R,2S)-2-[(2,2-difluoropropanoy)amino]-1-(2,3-dihydro-1,4-benzodioxin-6-yl)propyl]oxy}-1H-indazol-1-yl)-N-[(3S)-tetrahydrofuran-3-yl]benzamide,

3-(5-{[(1R,2S)-2-[(2,2-difluoropropanoyl)amino]-1-(2,3-dihydro-1,4-benzodioxin-6-yl)propyl]oxy}-1H-indazol-1-yl)-N-[(3R)-tetrahydrofuran-3-yl]benzamide,

3-(5-{[(1R,2S)-2-[(2,2-difluoropropanoyl)amino]-1-(2,3-dihydro-1,4-benzodioxin-6-yl)propyl]oxy}-1H-indazol-1-yl)-N-[(3RS)-tetrahydrofuran-3-yl]benzamide,

3-(5-{[2(2,2-difluoropropanoyl)amino]-1-(2,3-dihydro-1,4-benzodioxin-6-yl)propyl]oxy}-1H-indazol-1-yl)-N-[tetrahydrofuran-3-yl]benzamide,

3-[5-({(1R,2S)-1-(4H-1,3-Benzodioxin-7-yl)-2-[(2,2-difluoropropanoyl)amino]propyl}oxy)-1H-indazol-1-yl]-N-R3S)-tetrahydrofuran-3-yl]benzamide,

3-[5-({(1R,2S)-1-(4H-1,3-Benzodioxin-7-yl)-2-[(2,2-difluoropropanoyl)amino]propyl}oxy)-1H-indazol-1-yl]-N-[(3R)-tetrahydrofuran-3-yl]benzamide,

3-[5-({(1R,2S)-1-(4H-1,3-Benzodioxin-7-yl)-2-[(2,2-difluoropropanoyl)amino]propyl}oxy)-1H-indazol-1-yl]-N-[(3RS)-tetrahydrofuran-3-yl]benzamide,

3-[5-({1-(4H-1,3-Benzodioxin-7-yl)-2-[(2,2-difluoropropanoyl)amino]propyl}oxy)-1H-indazol-1-yl]-N-[tetrahydrofuran-3-yl]benzamide,

N-cyclopentyl-3-(5-{[(1R,2S)-2-[(2,2-difluoropropanoyl)amino]-1-(2,3-dihydro-1,4-benzodioxin-6-yl)propyl]oxy}-1H-indazol-1-yl)benzamide,

N-cyclopentyl-3-(5-{[2-[(2,2-difluoropropanoyl)amino]-1-(2,3-dihydro-1,4-benzodioxin-6-yl)propyl]oxy}-1H-indazol-1-yl)benzamide,

3-[5-({(1R,2S)-1-(4H-1,3-benzodioxin-7-yl)-2-[(2,2-difluoropropanoyl)amino]propyl}oxy)-1H-indazol-1-yl]-N-cyclopentylbenzamide,

3-[5-({1-(4H-1,3-benzodioxin-7-yl)-2-[(2,2-difluoropropanoyl)amino]propyl}oxy)-1H-indazol-1-yl]-N-cyclopentylbenzamide,

3-(5-{[(1R,2S)-2-[(2,2-difluoropropanoyl)amino]-1-(2,3-dihydro-1,4-benzodioxin-6-yl)propyl]oxy}-1H-indazol-1-yl)-N-[(1R,2S)-2-hydroxycyclopentyl]benzamide,

3-(5-{[(1R,2S)-2-[(2,2-difluoropropanoyl)amino]-1-(2,3-dihydro-1,4-benzodioxin-6-yl)propyl]oxy}-1H-indazol-1-yl)-N-[(1R)-2-hydroxycyclopentyl]benzamide,

3-(5-{[(1R,2S)-2-[(2,2-difluoropropanoyl)amino]-1-(2,3-dihydro-1,4-benzodioxin-6-ylpropyl]oxy}-1H-indazol-1-yl)-N-[(2S)-2-hydroxycyclopentyl]benzamide,

3-(5-{[2-[(2,2-difluoropropanoyl)amino]-1-(2,3-dihydro-1,4-benzodioxin-6-yl)propyl]oxy}-1H-indazol-1-yl)-N-[2-hydroxycyclopentyl]benzamide,

3-[5-({(1R,2S)-1-(4H-1,3-benzodioxin-7-yl)-2-[(2,2-difluoropropanoyl)amino]propyl}oxy)-1H-indazol-1-yl]-N-[(1R,2S)-2-hydroxycyclopentyl]benzamide,

3-[5-({(1R,2S)-1-(4H-1,3-benzodioxin-7-yl)-2-[(2,2-difluoropropanoyl)amino]propyl}oxy)-1H-indazol-1-yl]-N-[(1S,2R)-2-hydroxycyclopentyl]benzamide,

3-[5-({(1R,2S)-1-(4H-1,3-benzodioxin-7-yl)-2-[(2,2-difluoropropanoyl)amino]propyl}oxy)-1H-indazol-1-yl]-N-[(1S,2S)-2-hydroxycyclopentyl]benzamide,

3-[5-({(1R,2S)-1-(4H-1,3-benzodioxin-7-yl)-2-[(2,2-difluoropropanoyl)amino]propyl}oxy)-1H-indazol-1-yl]-N-[(1R,2R)-2-hydroxycyclopentyl]benzamide,

3-[5-({1-(4H-1,3-benzodioxin-7-yl)-2-[(2,2-difluoropropanoyl)amino]propyl}oxy)-1H-indazol-1-yl]-N-[2-hydroxycyclopentyl]benzamide,

3-[5-({(1R,2S)-1-(4H-1,3-benzodioxin-7-yl)-2-[(2,2-difluoropropanoyl)amino]propyl}oxy)-1H-indazol-1-yl]-N-[(2R)-2-hydroxybutyl]benzamide,

3-[5-({(1R,2S)-1-(4H-1,3-benzodioxin-7-yl)-2-[(2,2-difluoropropanoyl)amino]propyl}oxy)-1H-indazol-1-yl]-N-[(2S)-2-hydroxybutyl]benzamide,

3-[5-({1-(4H-1,3-benzodioxin-7-yl)-2-[(2,2-difluoropropanoyl)amino]propyl}oxy)-1H-indazol-1-yl]-N-[2-hydroxybutyl]benzamide,

3-(5-{[(1R,2S)-2-[(2,2-difluoropropanoyl)amino]-1-(2,3-dihydro-1,4-benzodioxin-6-yl)propyl]oxy}-1H-indazol-1-yl)-N-(pyridin-3-ylmethyl)benzamide,

3-(5-{[2-[(2,2-difluoropropanoyl)amino]-1-(2,3-dihydro-1,4-benzodioxin-6-yl)propyl]oxy}-1H-indazol-1-yl)-N-(pyridin-3-ylmethyl)benzamide,

3-[5-({(1R,2S)-1-(4H-1,3-benzodioxin-7-yl)-2-[(2,2-difluoropropanoyl)amino]propyl}oxy)-1H-indazol-1-yl]-N-(pyridin-3-ylmethyl)benzamide,

3-[5-({1-(4H-1,3-benzodioxin-7-yl)-2-[(2,2-difluoropropanoyl)amino]propyl}oxy)-1H-indazol-1-yl]-N-(pyridin-3-ylmethyl)benzamide,

3-[5-({(1R,2S)-1-(4H-1,3-benzodioxin-7-yl)-2-[(2,2-difluoropropanoyl)amino]propyl}oxy)-1H-indazol-1-yl]-N-[(3S)-1-oxidotetrahydrothiophen-3-yl]benzamide (Isomer1),

3-[5-({(1R,2S)-1-(4H-1,3-benzodioxin-7-yl)-2-[(2,2-difluoropropanoyl)amino]propyl}oxy)-1H-indazol-1-yl]-N-[(3R)-1-oxidotetrahydrothiophen-3-yl]benzamide (Isomer2),

3-[5-({(1R,2S)-1-(4H-1,3-benzodioxin-7-yl)-2-[(2,2-difluoropropanoyl)amino]propyl}oxy)-1H-indazol-1-yl]-N-[(3RS)-1-oxidotetrahydrothiophen-3-yl]benzamide,

3-[5-({1-(4H-1,3-benzodioxin-7-yl)-2-[(2,2-difluoropropanoyl)amino]propyl}oxy)-1H-indazol-1-yl]-N-[1-oxidotetrahydrothiophen-3-yl]benzamide,

3-[5-({(1R,2S)-1-(4H-1,3-benzodioxin-7-yl)-2-[(2,2-difluoropropanoyl)amino]propyl}oxy)-1H-indazol-1-yl]-N-benzylbenzamide,

3-[5-({1-(4H-1,3-benzodioxin-7-yl)-2-[(2,2-difluoropropanoyl)amino]propyl}oxy)-1H-indazol-1-yl]-N-benzylbenzamide,

3-(5-{[(1R,2S)-2-[(2,2-difluoropropanoyl)amino]-1-(2,3-dihydro-1,4-benzodioxin-6-yl)propyl]oxy}-1H-indazol-1-yl)-N-[(3R)-2-oxotetrahydrofuran-3-yl]benzamide,

3-(5-{[(1R,2S)-2-[(2,2-difluoropropanoyl)amino]-1-(2,3-dihydro-1,4-benzodioxin-6-yl)propyl]oxy}-1H-indazol-1-yl)-N-[(3S)-2-oxotetrahydrofuran-3-yl]benzamide,

3-(5-{[(1R,2S)-2-[(2,2-difluoropropanoyl)amino]-1-(2,3-dihydro-1,4-benzodioxin-6-yl)propyl]oxy}-1H-indazol-1-yl)-N-[(3SR)-2-oxotetrahydrofuran-3-yl]benzamide, and

3-(5-{[2-[(2,2-difluoropropanoyl)amino]-1-(2,3-dihydro-1,4-benzodioxin-6-yl)propyl]oxy}-1H-indazol-1-yl)-N-[2-oxotetrahydrofuran-3-yl]benzamide,

or a pharmaceutically acceptable salt thereof.

6. A pharmaceutical composition comprising a compound according to claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable adjuvant, diluent or carrier.

7. A method of treating a glucocorticoid receptor mediated disease state, an inflammatory condition, a respiratory condition, asthma and/or COPD in a mammal, which comprises administering to a mammal in need of such treatment an effective amount of a compound according to claim 1 , or a pharmaceutically acceptable salt thereof.

8. A combination of a compound according to claim 1 , or a pharmaceutically acceptable salt thereof, and one or more agents selected from the list comprising:

a PDE4 inhibitor;

a selective β.sub2. adrenoceptor agonist;

a muscarinic receptor antagonist;

a modulator of chemokine receptor function;

an inhibitor of p38 kinase function;

an inhibitor of matrix metalloproteases, for example targeting MMP-2, -9 or MMP-12; or

an inhibitor of neutrophil serine proteases, for example neutrophil elastase or proteinase 3.