Imidazolidine-2,4-dione derivatives and use thereof as a medicament

1. A compound of formula (I)

wherein:

R 1 represents a cyano, nitro, amino, —NHCOOR 4 or —NHCOR 4 radical;

R 2 represents a halo, alkyl, haloalkyl, or alkoxy radical;

R 3 represents an alkyl radical or a hydrogen atom; or the two R 3 radicals form together with the carbon atom to which they are attached a cycloalkyl comprising 3 to 4 members;

X represents

either a linear or branched alkylene chain with 3 to 7 carbon atoms, wherein the chain comprises one or more additional identical or different members chosen from —O—, —N(R 5 )—, —S—, —SO— or —SO 2 —;

or a

 group,

wherein n 1 and p 1 are two integers, the sum of n 1 +p 1 is an integer chosen from 2, 3, 4 or 5;

R 6 and R 7 form together a covalent bond, or R 6 and R 7 form together with the carbon atoms to which they are connected a

 ring or a cycloalkyl comprising 3 to 6 members;

R 4 represents an alkyl, aryl, or heteroaryl radical;

R 5 represents a hydrogen, an alkyl, or aralkyl radical;

or a pharmaceutically acceptable salt thereof.

2. The compound according to claim 1 , wherein X represents a linear or branched alkylene chain with 3 to 7 carbon atoms, wherein said chain comprises one or more additional identical or different members chosen from —O—, —(R 5 )—, —S—, —SO—, or —SO 2 —; or a pharmaceutically acceptable salt thereof.

3. The compound according to claim 1 , wherein X represents an alkylene chain comprising a single member chosen from —O—, —N(R 5 )—, —S—, —SO—, or —SO 2 —; or a pharmaceutically acceptable salt thereof.

4. The compound according to claim 1 , wherein X represents a

group,

wherein n 1 and p 1 are each integers, and the sum n 1 +p 1 is an integer chosen from 2, 3, 4 or 5;

R 6 and R 7 form together a covalent bond, or R 6 and R 7 form together with the carbon atoms to which they are connected a

 ring or a cycloalkyl comprising 3 to 4 members;

or a pharmaceutically acceptable salt thereof.

5. The compound according to claim 4 , wherein n 1 and p 1 are equal.

6. The compound according to claim 1 , wherein X represents a

group, and X′ represents an —O—, —N(R 5 )—, —S—, —SO—, —SO 2 —, —(CH 2 )— or

group, and n 2 and p 2 are integers the sum of which n 2 +p 2 is an integer chosen from 3, 4, 5, 6, or 7 when X′ represents an —O—, —N(R 5 )—, or —S—, —SO—, —SO 2 — group or an integer chosen from 2, 3, 4 or 5 when X′ represents a

or —(CH 2 )— group.

7. The compound according to claim 6 , in which X′ represents a

group.

8. The compound according to claim 6 , in which X′ represents an —O—, —N(R 5 )—, or —(CH 2 )— group.

9. The compound according to claim 6 , wherein n 2 and p 2 are equal.

10. The compound according to claim 1 , wherein R 3 represents an alkyl radical or the two R 3 radicals form together with the carbon atom to which they are attached a cycloalkyl comprising 3 to 4 members.

11. The compound according to claim 1 , wherein R 4 represents an alkyl radical.

12. The compound according to claim 1 , wherein R 5 represents an alkyl radical.

13. The compound according to claim 1 , wherein R 1 is in para position.

14. The compound according to claim 1 , wherein R 1 is in meta position.

15. The compound according to claim 1 , wherein R 6 and R 7 form together a covalent bond.

16. The compound according to claim 1 , wherein R 6 and R 7 form together with the carbon atoms to which they are connected the

ring.

17. The compound according to claim 1 , wherein R 6 and R 7 form together with the carbon atoms to which they are connected a cycloalkyl comprising 3 to 6 members.

18. The compound according to claim 1 , wherein the alkyl radical represents a methyl group.

19. A compound of formula (I) according to claim 1 , chosen from:

1,1′-butane-1,4-diylbis{5,5-dimethyl-3-[4-nitro-3-(trifluoromethyl)-phenyl]imidazolidine-2,4-dione};

1,1′-pentane-1,5-diylbis{5,5-dimethyl-3-[4-nitro-3-(trifluoromethyl)-phenyl]imidazolidine-2,4-dione};

1,1′-(oxydiethane-2,1-diyl)bis{5,5-dimethyl-3-[4-nitro-3-(trifluoromethyl)-phenyl]imidazolidine-2,4-dione};

4,4′-[pentane-1,5-diylbis(4,4-dimethyl-2,5-dioxoimidazolidine-3,1-diyl)]bis(2-methylbenzonitrile);

1,1′-(2Z)-but-2-ene-1,4-diylbis{5,5-dimethyl-3-[4-nitro-3-(trifluoromethyl)phenyl]imidazolidine-2,4-dione}; and

combinations thereof;

or a pharmaceutically acceptable salt thereof.

20. A compound of the formula (I), according to claim 1 , wherein the compound is 1,1′-pentane-1,5-diylbis{5,5-dimethyl-3-[4-nitro-3-(trifluoromethyl)-phenyl]imidazolidine-2,4-dione} or 1,1′-(2Z)-but-2-ene-1,4-diylbis{5,5-dimethyl-3-[4-nitro-3-(trifluoromethyl)phenyl]imidazolidine-2,4-dione} or a pharmaceutically acceptable salt thereof.

21. A method of preparing the compound according to claim 1 , comprising the steps of

(i) condensing two equivalents of the arylhydantoins of general formula (II)

in the presence of a strong base, wherein R 1 is a nitro or cyano group, with a derivative of general formula Gp 1 -X-Gp 2 ,

wherein Gp 1 and Gp 2 are leaving groups in the presence of a strong base,

in order to form the compound of general formula (I)

wherein and R 1 is a nitro or cyano group;

wherein, if R 1 is a nitro group, the method optionally further comprises a step of:

(ii) reducing the nitro group in order to obtain a compound of formula (III)

wherein the method optionally further comprises a step comprising:

(iii) reacting a compound of formula (III) obtained in stage (ii) with an acid chloride of general formula R 4 —COCl, in order to form a compound of formula (IV)

(iv) reacting a compound of formula (III) obtained in stage (ii) with a chloroformate of general formula R 4 —O—CO—Cl, in order to form a compound of formula (V)

if X in formula (I) represents a

 group where R 6 and R 7 form together a covalent bond, the method optionally further comprises a step of:

(v) oxidizing the compound of formula (I), wherein R 6 and R 7 form together a covalent bond, the double bond formed by R 6 and R 7 of the compound of formula (I) in order to obtain a compound of formula (VI)

22. A pharmaceutical composition comprising as an active ingredient, at least one compound of claim 1 , and a pharmaceutically acceptable excipient.

23. A method of treating prostate cancer comprising administering a therapeutically effective amount of a compound according to claim 22 .