4-oxadiazol-2-YL-indazoles as inhibitors of P13 kinases

1. A compound of formula (I):

wherein

R 1 is 9- or 10-membered bicyclic heteroaryl wherein the 9- or 10-membered bicyclic heteroaryl contains from one to three heteroatoms independently selected from oxygen and nitrogen and is optionally substituted by C 1-6 alkyl, C 3-6 cycloalkyl, halo, —CN or —NHSO 2 R 5 , or

pyridinyl optionally substituted by one or two substituents independently selected from C 1-6 alkyl, —OR 6 , halo and —NHSO 2 R 7 ;

X is —CH 2 NR 2 R 3 , C 1-6 alkyl, —CH 2 phenyl, —(CH 2 ) n OR 10 , —CH 2 SO 2 R 11 or —(CH 2 ) p C 3-6 cycloalkyl;

R 2 and R 3 , together with the nitrogen atom to which they are attached, are linked to form a 6- or 7-membered heterocyclyl or a 9- or 10-membered bicyclic heterocyclyl wherein the 6- or 7-membered heterocyclyl or the 9- or 10-membered bicyclic heterocyclyl optionally contains an oxygen atom, a sulphur atom or a further nitrogen atom and is optionally substituted by from one to three substituents independently selected from oxo, C 1-6 alkyl, —(CH 2 ) m NR 8 R 9 , phenyl optionally substituted by halo, and 6-membered heteroaryl wherein the 6-membered heteroaryl contains one or two nitrogen atoms,

a 7-membered bridged heterocyclyl wherein the 7-membered bridged heterocyclyl optionally contains a further nitrogen atom and is optionally substituted by from one to three substituents independently selected from C 1-6 alkyl, or

a 10-membered spiro bicyclic heterocyclyl wherein the 10-membered spiro bicyclic heterocyclyl optionally contains an oxygen atom, or

R 2 is hydrogen and R 3 is C 1-6 alkyl optionally substituted by one or two substituents independently selected from —OR 12 and —NR 13 R 14 ;

R 4 is hydrogen or methyl;

R 6 , R 12 and R 15 are each independently hydrogen or C 1-4 alkyl;

R 5 and R 7 are each independently C 1-6 alkyl or phenyl wherein the phenyl is optionally substituted by one or two substituents independently selected from halo and —OR 15 ;

R 8 and R 9 , together with the nitrogen atom to which they are attached, are linked to form a 5- or 6-membered heterocyclyl optionally containing an oxygen atom;

R 19 is hydrogen, C 1-6 alkyl, —(CH 2 ) q phenyl or C 3-6 cycloalkyl wherein the C 3-6 cycloalkyl is optionally substituted by one or two substituents independently selected from C 1-6 alkyl;

R 11 is C 1-6 alkyl or phenyl;

R 13 and R 14 , together with the nitrogen atom to which they are attached, are linked to form a 6-membered heterocyclyl optionally containing an oxygen atom;

m, p and q are each independently 0, 1 or 2; and

n is 1 or 2;

or a pharmaceutically acceptable salt thereof.

2. A compound according to claim 1 , or a salt thereof, wherein R 1 is 9- or 10-membered bicyclic heteroaryl wherein the 9- or 10-membered bicyclic heteroaryl contains one or two nitrogen atoms and is optionally substituted by C 1-6 alkyl or halo.

3. A compound according to claim 1 , or a salt thereof, wherein R 1 is pyridinyl optionally substituted by one or two substituents independently selected from C 1-6 alkyl, —OR 6 , halo and —NHSO 2 R 7 .

4. A compound according to claim 1 , or a salt thereof, wherein X is —CH 2 NR 2 R 3 .

5. A compound according to claim 1 , or a salt thereof, wherein R 4 is hydrogen.

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

4-(5-{[(2R,6S)-2,6-dimethyl-4-morpholinyl]methyl}-1,3,4-oxadiazol-2-yl)-6-(1H-indol-4-yl)-1H-indazole;

6-(1H-indol-4-yl)-4-(5-{[4-(1-methylethyl)-1-piperazinyl]methyl}-1,3,4-oxadiazol-2-yl)-1H-indazole;

N-[5-[4-(5-{[(2R,6S)-2,6-dimethyl-4-morpholinyl]methyl}-1,3,4-oxadiazol-2-yl)-1H-indazol-6-yl]-2-(methyloxy)-3-pyridinyl]methanesulfonamide;

N-[5-[1-methyl-4-(5-{[4-(1-methylethyl)-1-piperazinyl]methyl}-1,3,4-oxadiazol-2-yl)-1H-indazol-6-yl]-2-(methyloxy)-3-pyridinyl]methanesulfonamide;

N-[5-[4-(5-{[(2R,6S)-2,6-dimethyl-4-morpholinyl]methyl}-1,3,4-oxadiazol-2-yl)-1-methyl-1H-indazol-6-yl]-2-(methyloxy)-3-pyridinyl]methanesulfonamide; and

a salt thereof.

7. A compound according to claim 1 in the form of a pharmaceutically acceptable salt thereof.

8. A pharmaceutical composition comprising a compound as defined in claim 1 , or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable excipients.

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

6-(1H-indol-4-yl)-4-[5-(4-morpholinylmethyl)-1,3,4-oxadiazol-2-yl]-1H-indazole;

N-(2-chloro-5-{4-[5-(4-morpholinylmethyl)-1,3,4-oxadiazol-2-yl]-1H-indazol-6-yl}-3-pyridinyl)methanesulfonamide;

4-(5-{[(2R,6S)-2,6-dimethyl-4-morpholinyl]methyl}-1,3,4-oxadiazol-2-yl)-6-(1H-indol-4-yl)-1H-indazole;

6-(1H-indol-4-yl)-4-(5-{[4-(2-pyrimidinyl)-1-piperazinyl]methyl}-1,3,4-oxadiazol-2-yl)-1H-indazole;

4-{5-[(4,4-dimethyl-1-piperidinyl)methyl]-1,3,4-oxadiazol-2-yl}-6-(1H-indol-4-yl)-1H-indazole;

6-(1H-indol-4-yl)-4-(5-{[4-(2-methylpropyl)-1-piperazinyl]methyl}-1,3,4-oxadiazol-2-yl)-1H-indazole;

6-(1H-indol-4-yl)-4-(5-{[4-(1-methylethyl)-1-piperidinyl]methyl}-1,3,4-oxadiazol-2-yl)-1H-indazole;

6-(1H-indol-4-yl)-4-(5-{[2-(1-pyrrolidinylmethyl)-1-piperidinyl]methyl}-1,3,4-oxadiazol-2-yl)-1H-indazole;

4-(5-{[4-(4-fluorophenyl)-1-piperazinyl]methyl}-1,3,4-oxadiazol-2-yl)-6-(1H-indol-4-yl)-1H-indazole;

6-(1H-indol-4-yl)-4-(5-{[(1R,4R)-1,4,5-trimethyl-2,5-diazabicyclo[2.2.1]hept-2-yl]methyl}-1,3,4-oxadiazol-2-yl)-1H-indazole;

6-(1H-indol-4-yl)-4-(5-{[2-(1-pyrrolidinylmethyl)-4-morpholinyl]methyl}-1,3,4-oxadiazol-2-yl)-1H-indazole;

6-(1H-indol-4-yl)-4-[5-({4-[2-(4-morpholinyl)ethyl]-1-piperazinyl}methyl)-1,3,4-oxadiazol-2-yl]-1H-indazole;

6-(1H-indol-4-yl)-4-(5-{[4-(1-methylethyl)-1-piperazinyl]methyl}-1,3,4-oxadiazol-2-yl)-1H-indazole;

4-(5-{[(2R,6S)-2,6-dimethyl-1-piperidinyl]methyl}-1,3,4-oxadiazol-2-yl)-6-(1H-indol-4-yl)-1H-indazole;

4-(5-{[(1S,4S)-1,4-dimethyl-7-azabicyclo[2.2.1]hept-7-yl]methyl}-1,3,4-oxadiazol-2-yl)-6-(1H-indol-4-yl)-1H-indazole;

4-({5-[6-(1H-indol-4-yl)-1H-indazol-4-yl]-1,3,4-oxadiazol-2-yl}methyl)octahydro-2H-1,4-benzoxazine;

6-(1H-indol-4-yl)-4-(5-{[2-(2-methylpropyl)-4-morpholinyl]methyl}-1,3,4-oxadiazol-2-yl)-1H-indazole;

N-{2-chloro-5-[4-(5-{[4-(1-methylethyl)-1-piperazinyl]methyl}-1,3,4-oxadiazol-2-yl)-1H-indazol-6-yl]-3-pyridinyl}methanesulfonamide;

N-{2-chloro-5-[4-(5-{[(2R,6S)-2,6-dimethyl-4-morpholinyl]methyl}-1,3,4-oxadiazol-2-yl)-1H-indazol-6-yl]-3-pyridinyl}methanesulfonamide;

N-(2-chloro-5-{4-[5-(4-morpholinylmethyl)-1,3,4-oxadiazol-2-yl]-1H-indazol-6-yl}-3-pyridinyl)methanesulfonamide;

N-[5-[4-(5-{[(2R,6S)-2,6-dimethyl-4-morpholinyl]methyl}-1,3,4-oxadiazol-2-yl)-1H-indazol-6-yl]-2-(methyloxy)-3-pyridinyl]methanesulfonamide;

N-[5-[4-(5-{[4-(1-methylethyl)-1-piperazinyl]methyl}-1,3,4-oxadiazol-2-yl)-1H-indazol-6-yl]-2-(methyloxy)-3-pyridinyl]methanesulfonamide;

4-(5-{[(2R,6S)-2,6-dimethyl-4-morpholinyl]methyl}-1,3,4-oxadiazol-2-yl)-6-(1H-indol-4-yl)-1-methyl-1H-indazole;

6-(1H-indol-4-yl)-1-methyl-4-(5-{[4-(1-methylethyl)-1-piperazinyl]methyl}-1,3,4-oxadiazol-2-yl)-1H-indazole;

N-[5-[1-methyl-4-(5-{[4-(1-methylethyl)-1-piperazinyl]methyl}-1,3,4-oxadiazol-2-yl)-1H-indazol-6-yl]-2-(methyloxy)-3-pyridinyl]methanesulfonamide;

N-[5-[4-(5-{[(2R,6S)-2,6-dimethyl-4-morpholinyl]methyl}-1,3,4-oxadiazol-2-yl)-1-methyl-1H-indazol-6-yl]-2-(methyloxy)-3-pyridinyl]methanesulfonamide;

N-[5-[4-(5-{[(2R,6S)-2,6-dimethyl-4-morpholinyl]methyl}-1,3,4-oxadiazol-2-yl)-1H-indazol-6-yl]-2-(methyloxy)-3-pyridinyl]-2,4-difluorobenzenesulfonamide;

N-[5-(4-{5-[(2,2-dimethyl-4-morpholinyl)methyl]-1,3,4-oxadiazol-2-yl]-1H-indazol-6-yl)-2-(methyloxy)-3-pyridinyl}methanesulfonamide;

6-(1H-indol-4-yl)-4-[5-(1-methylethyl)-1,3,4-oxadiazol-2-yl]-1H-indazole;

4-(5-cyclohexyl-1,3,4-oxadiazol-2-yl)-6-(1H-indol-4-yl)-1H-indazole;

4-[5-(cyclohexylmethyl)-1,3,4-oxadiazol-2-yl]-6-(1H-indol-4-yl)-1H-indazole;

6-(1H-indol-4-yl)-4-[5-(phenylmethyl)-1,3,4-oxadiazol-2-yl]-1H-indazole;

6-(1H-indol-4-yl)-4-{5-[2-(methyloxy)ethyl]-1,3,4-oxadiazol-2-yl}-1H-indazole;

6-(1H-indol-4-yl)-4-(5-{[(phenylmethyl)oxy]methyl}-1,3,4-oxadiazol-2-yl)-1H-indazole;

6-(1H-indol-4-yl)-4-[5-({[(1R,2S,5R)-5-methyl-2-(1-methylethyl)cyclohexyl]oxy}methyl)-1,3,4-oxadiazol-2-yl]-1H-indazole;

{5-[6-(1H-indol-4-yl)-1H-indazol-4-yl]-1,3,4-oxadiazol-2-yl}methanol;

6-(1H-Indol-4-yl)-4-{5-[(methyloxy)methyl]-1,3,4-oxadiazol-2-yl}-1H-indazole;

6-(1H-indol-4-yl)-4-(5-methyl-1,3,4-oxadiazol-2-yl)-1H-indazole;

N-{2-chloro-5-[4-(5-methyl-1,3,4-oxadiazol-2-yl)-1H-indazol-6-yl]-3-pyridinyl}methanesulfonamide;

6-(1H-indol-4-yl)-4-{5-[(methylsulfonyl)methyl]-1,3,4-oxadiazol-2-yl}-1H-indazole;

6-(1H-indol-4-yl)-4-{5-[(phenylsulfonyl)methyl]-1,3,4-oxadiazol-2-yl}-1H-indazole;

N-(2-(methyloxy)-5-{4-[5-(6-oxa-9-azaspiro[4.5]dec-9-ylmethyl)-1,3,4-oxadiazol-2-yl]-1H-indazol-6-yl}-3-pyridinyl)methanesulfonamide;

2-[({5-[6-(1H-indol-4-yl)-1H-indazol-4-yl]-1,3,4-oxadiazol-2-yl}methyl)amino]ethanol;

1-[({5-[6-(1H-indol-4-yl)-1H-indazol-4-yl]-1,3,4-oxadiazol-2-yl}methyl)amino]-3-(4-morpholinyl)-2-propanol;

N-[5-[4-(5-{[(3R,5S)-3,5-dimethyl-4-(1-methylethyl)-1-piperazinyl]methyl]-1,3,4-oxadiazol-2-yl)-1H-indazol-6-yl]-2-(methyloxy)-3-pyridinyl}methanesulfonamide;

N-[5-(4-{5-[(1,1-dioxido-4-thiomorpholinyl)methyl]-1,3,4-oxadiazol-2-yl]-1H-indazol-6-yl)-2-(methyloxy)-3-pyridinyl}methanesulfonamide;

N-[5-(4-{5-[(2-ethyl-4-morpholinyl)methyl]-1,3,4-oxadiazol-2-yl]-1H-indazol-6-yl)-2-(methyloxy)-3-pyridinyl}methanesulfonamide;

9-({5-[6-(1H-indol-4-yl)-1H-indazol-4-yl]-1,3,4-oxadiazol-2-yl}methyl)-6-oxa-9-azaspiro[4.5]decane;

4-{5-[(2,2-dimethyl-4-morpholinyl)methyl]-1,3,4-oxadiazol-2-yl}-6-(1H-indol-4-yl)-1H-indazole;

N-[5-[4-(5-{[(3R,5S)-3,5-dimethyl-4-(1-methylethyl)-1-piperazinyl]methyl]-1,3,4-oxadiazol-2-yl)-1H-indazol-6-yl]-2-(methyloxy)-3-pyridinyl}-2,4-difluorobenzenesulfonamide;

2,4-difluoro-N-[5-[4-(5-{[4-(1-methylethyl)-1-piperazinyl]methyl}-1,3,4-oxadiazol-2-yl)-1H-indazol-6-yl]-2-(methyloxy)-3-pyridinyl]benzenesulfonamide;

N-[5-(4-{5-[(2-methyl-4-morpholinyl)methyl]-1,3,4-oxadiazol-2-yl]-1H-indazol-6-yl)-2-(methyloxy)-3-pyridinyl}methanesulfonamide;

6-(1H-indol-4-yl)-4-{5-[(2-methyl-4-morpholinyl)methyl]-1,3,4-oxadiazol-2-yl}-1H-indazole;

N-({5-[6-(1H-indol-4-yl)-1H-indazol-4-yl]-1,3,4-oxadiazol-2-yl}methyl)-3-(4-morpholinyl)-1-propanamine;

N-(2-(methyloxy)-5-{4-[5-(tetrahydro-1,4-oxazepin-4(5H)-ylmethyl)-1,3,4-oxadiazol-2-yl]-1H-indazol-6-yl}-3-pyridinyl)methanesulfonamide;

6-(1H-indol-4-yl)-4-[5-(tetrahydro-1,4-oxazepin-4(5H)-ylmethyl)-1,3,4-oxadiazol-2-yl]-1H-indazole;

N-[5-{4-[5-({[2-hydroxy-3-(4-morpholinyl)propyl]amino}methyl)-1,3,4-oxadiazol-2-yl]-1H-indazol-6-yl]-2-(methyloxy)-3-pyridinyl}methanesulfonamide;

2,4-difluoro-N-[5-{4-[5-({[2-hydroxy-3-(4-morpholinyl)propyl]amino}methyl)-1,3,4-oxadiazol-2-yl]-1H-indazol-6-yl]-2-(methyloxy)-3-pyridinyl}benzenesulfonamide;

N-[5-(4-{5-[(8aS)-hexahydropyrrolo[1,2-a]pyrazin-2(1H)-ylmethyl]-1,3,4-oxadiazol-2-yl]-1H-indazol-6-yl)-2-(methyloxy)-3-pyridinyl}methanesulfonamide;

2,4-difluoro-N-[5-(4-{5-[(8aS)-hexahydropyrrolo[1,2-a]pyrazin-2(1H)-ylmethyl]-1,3,4-oxadiazol-2-yl}-1H-indazol-6-yl)-2-(methyloxy)-3-pyridinyl]benzenesulfonamide;

N-[5-[4-(5-{[(2R,6S)-2,6-dimethyl-4-morpholinyl]methyl}-1,3,4-oxadiazol-2-yl)-1-methyl-1H-indazol-6-yl]-2-(methyloxy)-3-pyridinyl]-2,4-difluorobenzenesulfonamide;

N-[5-[4-(5-{[(2R,6S)-2,6-dimethyl-4-morpholinyl]methyl}-1,3,4-oxadiazol-2-yl)-1H-indazol-6-yl]-2-(methyloxy)-3-pyridinyl]-2-(methyloxy)benzenesulfonamide;

and a pharmaceutically acceptable salt thereof.