Androgen receptor modulating compounds

1. A compound of formula (I):

wherein

R 1 is hydrogen, halogen, cyano, nitro or optionally substituted 5- or 6-membered heterocyclic ring;

R 2 is hydrogen, halogen, cyano, nitro, amino, C 1-7 alkyl, halo C 1-7 alkyl, hydroxy C 1-7 alkyl, thio C 1-7 alkyl or C 1-7 alkoxy;

R 3 is hydrogen, halogen or C 1-7 alkyl,

or R 2 and R 3 together with the carbon atoms to which they are attached form a optionally substituted 5- or 6-membered carbocyclic or heterocyclic ring;

wherein at least two of R 1 , R 2 and R 3 are not hydrogen;

R 4 , R 4′ , R 5 , R 6 ; and R 7 are, independently, hydrogen, C 1-7 alkyl, halo C 1-7 alkyl or hydroxy C 1-7 alkyl;

ring atom E is C or N;

dashed line means an optional double bond;

A is a 5-12 membered heterocyclic ring;

B is a 5-membered heterocyclic ring wherein 1-3 of the members are heteroatoms selected from N, O and S;

R 8 is hydrogen, hydroxy, halogen, nitro, amino, cyano, oxo, C 1-7 alkyl, C 1-7 alkoxy, halo C 1-7 alkyl, hydroxy C 1-7 alkyl, cyano C 1-7 alkyl, amino C 1-7 alkyl, oxo C 1-7 alkyl, C 1-7 alkoxy C 1-7 alkyl, methylsulfonamido C 1-7 alkyl, oxiran C 1-7 alkyl, C 1-7 alkylamino, hydroxy C 1-7 alkylamino, C 1-7 alkoxy C 1-7 alkylamino, C 1-7 alkylamino C 1-7 alkyl, hydroxy C 1-7 alkylamino C 1-7 alkyl, hydroxyimino C 1-7 alkyl, halo C 1-7 alkylhydroxy C 1-7 alkyl, —C(O)R 10 , —OC(O)R 17 , —NH—C(O)R 18 or an optionally substituted 5-12 membered carbocyclic or heterocyclic ring, each group optionally linked to A-ring via C 1-7 alkylene linker;

R 9 is hydrogen, halogen, C 1-7 alkyl, oxo, hydroxy C 1-7 alkyl, oxo C 1-7 alkyl or an optionally substituted 5 or 6 membered carbocyclic or heterocyclic ring, each group optionally linked to A-ring via C 1-7 alkylene linker;

R 10 is hydrogen, hydroxy, C 1-7 alkyl, hydroxy C 1-7 alkyl, halo C 1-7 alkyl, C 1-7 alkoxy, NR 11 R 12 , or an optionally substituted 5-12 membered carbocyclic or heterocyclic ring;

R 11 is hydrogen, C 1-7 alkyl, hydroxy C 1-7 alkyl, amino C 1-7 alkyl, C 1-7 alkyl amino C 1-7 alkyl,

R 12 is hydrogen or C 1-7 alkyl;

R 13 and R 14 are, independently, hydrogen, C 1-7 alkyl, halogen, cyano or hydroxy C 1-7 alkyl;

R 15 and R 16 are, independently, hydrogen, oxo, thioxo, C 1-7 alkyl or cyano;

R 17 is C 1-7 alkyl, C 1-7 alkoxy, amino C 1-7 alkyl or C 1-7 alkylamino C 1-7 alkyl;

R 18 is C 1-7 alkyl, amino C 1-7 alkyl or C 1-7 alkylamino C 1-7 alkyl;

or a pharmaceutically acceptable salt thereof.

2. The compound according to claim 1 , wherein B is

wherein Z is O, N, C═O or C═S;

X is C or N;

Y is C or N;

G is CH, C═O or C═S;

M is CH or 0;

R 13 and R 14 are, independently, hydrogen, C 1-7 alkyl, halogen, cyano or hydroxy C 1-7 alkyl;

dashed line means an optional double bond, and the asterisk denotes the point of attachment to the ring.

3. The compound according to claim 1 , wherein B is a group of formula (2′), (3′) or (4′)

wherein

R 13 and R 14 are, independently, hydrogen, C 1-7 alkyl, halogen, cyano or hydroxy C 1-7 alkyl; and

the asterisk denotes the point of attachment to the ring.

4. The compound according to claim 1 , wherein ring A is anyone of the following groups or tautomers thereof

5. The compound according to claim 4 , wherein

ring atom E is C,

R 1 is halogen, C 1-7 alkyl, cyano, nitro or halo C 1-7 alkyl,

R 2 is cyano, halogen or nitro,

R 3 is hydrogen, halogen or C 1-7 alkyl,

A is anyone of groups (5′), (6′), (7′), (8′), (12′), (20′), (21′), (27′) and (28′) or tautomers thereof,

B is a group of formula (2′), (3′) or (4′)

substituted by R 13 and R 14 , which are hydrogen,

R 4 (and R 4 ′ if applicable) is hydrogen or methyl,

R 5 is hydrogen or C 1-7 alkyl,

R 6 (if applicable) is hydrogen,

R 8 is hydrogen, C 1-7 alkyl, hydroxy C 1-7 alkyl, halogen, hydroxyimino C 1-7 alkyl, a 5 or 6 membered heterocyclic ring or —C(O)R 10 wherein R 10 is C 1-7 alkyl, and

R 9 is hydrogen, halogen or C 1-7 alkyl.

6. A pharmaceutical composition comprising a compound of claim 1 together with a pharmaceutically acceptable carrier.

7. A method for the treatment or prevention of androgen receptor dependent conditions, comprising administering to a subject in need thereof a therapeutically effective amount of a compound of claim 1 .

8. A method according to claim 7 , wherein the androgen receptor dependent condition is prostate cancer.

9. A method for the treatment or prevention of androgen receptor dependent conditions, comprising administering to a subject in need thereof a therapeutically effective amount of a compound of formula (I′)

wherein

R 1 is hydrogen, halogen, cyano, nitro or optionally substituted 5- or 6-membered heterocyclic ring;

R 2 is hydrogen, halogen, cyano, nitro, amino, C 1-7 alkyl, halo C 1-7 alkyl, hydroxy C 1-7 alkyl, thio C 1-7 alkyl or C 1-7 alkoxy;

R 3 is hydrogen, halogen or C 1-7 alkyl,

or R 2 and R 3 together with the carbon atoms to which they are attached form a optionally substituted 5- or 6-membered carbocyclic or heterocyclic ring;

wherein at least two of R 1 , R 2 and R 3 are not hydrogen;

R 4 , R 4′ , R 5 , R 6 ; and R 7 are, independently, hydrogen, C 1-7 alkyl, halo C 1-7 alkyl or hydroxy C 1-7 alkyl:

ring atom E is C or N;

is C or N;

dashed line means an optional double bond;

A is a 5-12 membered heterocyclic ring;

B is a 5-membered heterocylic ring wherein 1-3 of the members are heteroatoms selected from N, 0 and S;

R 8 is hydrogen, hydroxy, halogen, nitro, amino, cyano, oxo, C 1-7 alkyl, C 1-7 alkoxy, halo C 1-7 alkyl, hydroxy C 1-7 alkyl, cyano C 1-7 alkyl, amino C 1-7 alkyl, oxo C 1-7 alkyl, C 1-7 alkoxy C 1-7 , alkyl, methylsulfonamido C 1-7 alkyl, oxiran C 1-7 alkyl, C 1-7 alkylamino hydroxy C 1-7 alkylamino, C 1-7 alkoxy C 1-7 alkylamino, C 1-7 alkylamino C 1-7 alkyl, hydroxy C 1-7 alkylamino C 1-7 alkyl, hydroxyimino C 1-7 alkyl, halo C 1-7 alkylhydroxy C 1-7 alkyl, —C(O)R 10 , —OC(O)R 17 , —NH—C(O)R 18 or an optionally substituted 5-12 membered carbocyclic or heterocyclic ring, each aroup optionally linked to A-ring via C 1-7 alkylene linker;

R 9 is hydrogen, halogen C 1-7 alkyl, oxo, or an optionally substituted 5 or 6 membered carbocyclic or heterocyclic ring, each group optionally linked to A-ring via C 1-7 alkylene linker;

R 10 is hydrogen, hydroxy, C 1-7 alkyl, hydroxy C 1-7 alkyl, halo C 1-7 , alkyl, C 1-7 alkoxy, NR 11 R 12 , or an optionally substituted 5-12 membered carbocyclic or heterocyclic ring;

R 11 is hydrogen, C 1-7 alkyl hydroxy C 1-7 alkyl, amino C 1-7 alkyl, C 1-7 alkyl amino C 1-7 alkyl,

R 12 is hydrogen or C 1-7 alkyl;

R 13 and R 14 are, independently, hydrogen, C 1-7 alkyl, halogen, cyano, halogen C 1-7 alkyl or hydroxy C 1-7 alkyl;

R 15 and R 16 are, independently, hydrogen, oxo, thioxo, C 1-7 alkyl or cyano;

R 17 alkyl, C 1-7 alkoxy, amino C 1-7 alkyl or C 1-7 alkylamino C 1-7 alkyl;

R 18 is C 1-7 alkyl, amino C 1-7 alkyl or C 1-7 akylamino C 1-7 alkyl;

or a pharmaceutically acceptable salt thereof.

10. The method according to claim 9 , wherein the androgen receptor dependent condition is prostate cancer.