Bicyclic derivatives for use in the treatment of androgen receptor associated conditions-155

1. A compound of Formula (If), or a pharmaceutically acceptable salt thereof:

wherein

Y represents CH, COH or N;

k represents 0, 1 or 2;

J represents:

phenyl or naphthyl;

a totally saturated monocyclic 3 to 6 membered carbocyclic ring;

furanyl, imidazolyl, isothiazolyl, morpholinyl, oxadiazolyl, oxazolyl, isoxazolyl, oxetanyl, tetrahydro-2H-pyranyl, pyrazolyl, pyridazinyl, pyridinyl, pyrrolyl or thiadiazolyl; or

a bicyclic 9 membered heteroaryl ring system which comprises 1 or 2 nitrogen atoms, 1 or 2 oxygen atoms, 1 sulphur atom, or 1 nitrogen atom and 1 sulphur atom;

L 3 represents a direct bond, —(CR 9 R 10 ) t —, —C(O)N(R 11 )—(CH 2 ) q —, —C(O)N(R 11 )—(CH 2 ) q —S(O) 2 —, —C(O)—(CH 2 ) q —, —O—(CH 2 ) q —, —O—(CH 2 ) q —NR 11 —(CH 2 ) q —, —O—(CH 2 ) q —C(O)NR 11 —(CH 2 ) q —, —S—, —S(O)— or —S(O) 2 —;

R 9 and R 10 , identically or differently on each occurrence, represent hydrogen or methyl;

q, identically or differently on each occurrence, represents 0, 1, 2 or 3;

t represents 1, 2 or 3;

R 11 represents hydrogen or methyl;

R 12 represents:

halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, carboxy, C 1-6 alkoxy, fluoroC 1-6 alkyl, hydroxy, amino, N—C 1-4 alkylamino or N,N-di-C 1-4 alkylamino;

phenyl or naphthyl, wherein the phenyl or naphthyl ring is optionally substituted with 1, 2 or 3 substituents selected from R 13 ;

a monocylic 5 or 6 membered heteroaryl ring which comprises 1, 2, 3 or 4 heteroatoms independently selected from O, N or S and wherein the heteroaryl ring is optionally substituted with 1, 2 or 3 substituents selected from R 13 ; or

a monocylic 4, 5, 6 or 7 membered heterocylic ring which comprises 1, 2, 3 or4 heteroatoms independently selected from O, N or S and wherein the heterocyclic ring is optionally substituted with 1, 2 or 3 substituents selected from R 13 ;

R 13 represents amino, halo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 2-6 alkanoyl, C 1-6 alkoxyC 1-6 alkyl, carboxy, cyano, oxo, fluoroC 1-6 alkyl, hydroxy, hydroxyC 1-6 alkyl, C 1-6 alkylsulphanyl, C 1-6 alkylsulphinyl, C 1-6 alkylsulphonyl, N—C 1-4 alkylamino, N,N-di-C 1-4 alkylamino or —C(O)NR 14 R 15 wherein R 14 and R 15 independently represent hydrogen or methyl;

r represents 1, 2 or 3 when J represents phenyl or naphthyl;

r represents 0 when J represents a totally saturated monocyclic 3 to 6 membered carbocyclic ring; and

r represents 0, 1, 2 or 3 when J represents furanyl, imidazolyl, isothiazolyl, morpholinyl, oxadiazolyl, oxazolyl, isoxazolyl, oxetanyl, tetrahydro-2H-pyranyl, pyrazolyl, pyridazinyl, pyridinyl, pyrrolyl, thiadiazolyl, or a bicyclic 9 membered heteroaryl ring system which comprises 1 or 2 nitrogen atoms, 1 or 2 oxygen atoms, 1 sulphur atom, or 1 nitrogen atom and 1 sulphur atom;

with the proviso that the compound of Formula (If) is other than:

4-{4-[3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperazin-1-yl}phenol;

6-[4-(1H-indol-3-yl)piperidin-1-yl]-3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazine;

6-[4-(2,6-dimethylphenyl)piperazin-1-yl]-3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazine;

6-[4-(4-methoxyphenyl)piperazin-1-yl]-3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazine;

6-[4-(3-chlorophenyl)piperazin-1-yl]-3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazine; or

6-[4-(4-fluorophenyl)piperazin-1-yl]-3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazine.

2. A compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein Y represents CH or COH.

3. A compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein Y represents N.

4. A compound according to any one of claims 1 to 3 , or a pharmaceutically acceptable salt thereof, wherein J represents phenyl, pyridinyl, indolyl, indazolyl or pyrrolopyridinyl.

5. A compound according to any one of claims 1 to 3 , or a pharmaceutically acceptable salt thereof, wherein L 3 represents —C(O)N(R 11 )—(CH 2 ) q —, —NR 11 C(O)—(CH 2 ) q —, —C(O)—(CH 2 ) q —, or —O—(CH 2 ) q —.

6. A compound according to claim 5 , or a pharmaceutically acceptable salt thereof, wherein R 11 represents methyl.

7. A compound according to claim 5 , or a pharmaceutically acceptable salt thereof, wherein L 3 represents —O—CH 2 —CH 2 —.

8. A compound according to any one of claims 1 to 3 , or a pharmaceutically acceptable salt thereof, wherein R 12 represents fluoro, chloro, methyl, methoxy, difluoromethyl, trifluoromethyl, cyano, hydroxy, pyrrolidinyl, piperidinyl, piperazinyl, methylsulphonyl, morpholinyl or pyrazolyl.

9. A compound according to any one of claims 1 to 3 , or a pharmaceutically acceptable salt thereof, wherein R 12 represents pyrazolyl.

10. A compound according to any one of claims 1 to 3 , or a pharmaceutically acceptable salt thereof, wherein R 13 represents methyl, oxo or hydroxy.

11. A compound according to any one of claims 1 to 3 , or a pharmaceutically acceptable salt thereof, wherein r represents 1.

12. A compound according to any one of claims 1 to 3 , or a pharmaceutically acceptable salt thereof, wherein J does not represent phenyl or naphthyl and r represents 0.

13. A compound according to claim 1 selected from:

4-pyridin-3-yl-1-[3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-ol;

N-(2-methoxyethyl)-N-methyl-4-[1-[3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-yl]benzamide;

6-[4-[4-[2-(1-methyl-1H-pyrazol-5-yl)ethoxy]phenyl]piperidin-1-yl]-3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazine;

6-[4-[4-[2-(1-methyl-1H-pyrazol-5-yl)ethoxy]phenyl]piperazin-1-yl]-3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazine; and

4-[4-[2-(1-methyl-1H-pyrazol-5-yl)ethoxy]phenyl]-1-[3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-ol;

and pharmaceutically acceptable salts thereof.

14. A pharmaceutical composition which comprises a compound according to any one of claims 1 to 3 or 13 , or a pharmaceutically acceptable salt thereof, in association with a pharmaceutically acceptable diluent or carrier.

15. A process for the preparation of compounds of Formula (If) which comprises reacting a compound of Formula (IIb), wherein G represents halogen, with an amine of Formula (IIIb), wherein Y, J, L 3 , R 12 , k and r are as defined hereinbefore in relation to Formula (If):

and thereafter, if necessary:

(i) converting a functional group of one compound of the invention into another functional group;

(ii) introducing a new functional group into one compound of the invention;

(iii) removing any protecting groups;

(iv) for compounds of the invention in the form of a single enantiomer separating a racemic compound of the invention into separate enantiomers;

(v) preparing a pharmaceutically acceptable salt thereof; and/or

(vi) preparing a crystalline form thereof.