Indolizine derivatives, method for preparing same, and therapeutic compositions comprising same

1. A compound of the formula (I):

in which:

X represents a —(CH 2 ) n — radical where n is a whole number from 1 to 6, or a group with formula CH 2 —Z—(CH 2 ) 2 —, in which Z represents an O(CH 2 ) m — group in which m is a whole number from 0 to 3; R 1 represents a linear, branched or cyclic C 1 -C 8 alkyl radical; Am represents an NR 3 R 4 group in which R 3 and R 4 are identical or different and independently of each other represent:

a hydrogen atom;

a linear, branched or cyclic C 1 -C 6 alkyl radical or a C 1 -C 3 radical substituted with a C 3 -C 6 cycloalkyl radical;

or a (CH 2 ) i —O—B radical in which B represents a hydrogen atom or a (CH 2 ) k H alkyl radical, where l and k are whole numbers, l≧2 and l+k≦6;

or R 3 and R 4 together with the nitrogen atom to which they are attached form a heterocycle containing 4 to 6 links which may optionally contain one or more heteroatoms selected from N and O and optionally carrying one or more substituents selected from a linear, branched or cyclic C 1 -C 6 alkyl radical;

R 2 represents a hydrogen atom or a linear, branched or cyclic C 1 -C 6 alkyl radical;

and their pharmaceutically acceptable salts.

2. A compound according to claim 1 , wherein X represents a —(CH 2 ) n — radical where n is a whole number from 1 to 6.

3. A compound according to claim 1 , wherein X represents a (CH 2 ) n — radical where n is a whole number from 3 to 4.

4. A compound according to claim 1 , wherein X represents a group with formula CH 2 —Z—(CH 2 ) 2 —, in which Z represents an O(CH 2 ) m — group in which m is a whole number from 0 to 3.

5. Indolizine derivatives according to claim 1 wherein R 1 represents a C 1 -C 4 alkyl radical.

6. A compound according to claim 1 , wherein R 3 and R 4 independently of each other represent a linear C 1 -C 4 alkyl radical.

7. A compound according to claim 1 , wherein R 3 and R 4 together form a piperidinyl or piperazinyl group optionally carrying one or more methyl radicals.

8. A compound according to claim 1 , wherein R 2 represents a hydrogen atom.

9. A compound according to claim 1 , wherein the pharmaceutically acceptable salt is selected from an oxalate and a hydrochloride.

10. A compound of formula (I) selected from:

(2-butylindolizin-3-yl){4-[3-(diethylamino)propyl]phenyl}methanone hydrochloride;

(2-ethylindolizin-3-yl){4-[3-(diethylamino)propyl]phenyl}methanone oxalate;

{4-[3-(diethylamino)propyl]phenyl}(2-propylindolizin-3-yl)methanone hydrochloride;

(2-butylindolizin-3-yl){4-[4-(diethylamino)butyl]phenyl}methanone oxalate;

{4-[4-(diethylamino)butyl]phenyl}(2-ethylindolizin-3-yl)methanone oxalate;

{4-[4-(diethylamino)butyl]phenyl}(2-propylindolizin-3-yl)methanone hydrochloride;

(2-butylindolizin-3-yl){4-[3-(dipropylamino)propyl]phenyl}methanone hydrochloride;

(2-butylindolizin-3-yl){4-[3-(dipropylamino)propyl]phenyl}methanone hydrochloride hemihydrate;

(2-butylindolizin-3-yl){4-[3-(dipropylamino)propyl]phenyl}methanone sulphate;

(2-butylindolizin-3-yl){4-[3-(dipropylamino)propyl]phenyl}methanone fumarate;

{4-[3-(dipropylamino)propyl]phenyl}(2-ethyl indolizin-3-yl)methanone hydrochloride;

{4-[3-(dipropylamino)propyl]phenyl}(2-propylindolizin-3-yl)methanone hydrochloride;

(2-butylindolizin-3-yl){4-[4-(dipropylamino)butyl]phenyl}methanone hydrochloride;

{4-[4-(dipropylamino)butyl]phenyl}(2-ethylindolizin-3-yl)methanone hydrochloride;

4-[3-(dipropylamino)propyl]phenyl}(2-isopropylindolizin-3-yl)methanone hydrochloride;

{4-[3-(dipropylamino)propyl]phenyl}(2-methylindolizin-3-yl)methanone hydrochloride;

{4-[4-(dipropylamino)butyl]phenyl}(2-isopropylindolizin-3-yl)methanone oxalate;

{4-[4-(dipropylamino)butyl]phenyl}(2-methylindolizin-3-yl)methanone hydrochloride;

{4-[4-(dipropylamino)butyl]phenyl}(2-propylindolizin-3-yl)methanone hydrochloride;

(2-butylindolizin-3-yl){4-[3-(dibutylamino)propyl]phenyl}methanone hydrochloride;

Hydrochloride {4-[3-(dibutylamino)propyl]phenyl}(2-ethylindolizin-3-yl)methanone;

{4-[3-(dibutylamino)propyl]phenyl}(2-propylindolizin-3-yl)methanone hydrochloride;

(2-butylindolizin-3-yl){4-[4-(dibutylamino)butyl]phenyl}methanone oxalate;

{4-[4-(dibutylamino)butyl]phenyl}(2-ethylindolizin-3-yl)methanone oxalate;

{4-[4-(dibutylamino)butyl]phenyl}(2-propylindolizin-3-yl)methanone oxalate;

(2-butylindolizin-3-yl)(4-{3-[ethyl(propyl)amino]propyl}phenyl)methanone hydrochloride;

(2-ethylindolizin-3-yl)(4-{3-[ethyl(propyl)amino]propyl}phenyl)methanone oxalate;

(4-{3-[ethyl(propyl)amino]propyl}phenyl)(2-isopropylindolizin-3-yl)methanone hydrochloride;

(4-{3-[ethyl(propyl)amino]propyl}phenyl)(2-methylindolizin-3-yl)methanone hydrochloride;

(4-{4-[ethyl(propyl)amino]butyl}phenyl)(2-isopropylindolizin-3-yl)methanone oxalate;

(4-{4-[ethyl(propyl)amino]butyl}phenyl)(2-methylindolizin-3-yl)methanone hydrochloride;

(4-{3-[ethyl(propyl)amino]propyl}phenyl)(2-propylindolizin-3-yl)methanone hydrochloride;

(2-butylindolizin-3-yl)(4-{4-[ethyl(propyl)amino]butyl}phenyl)methanone hydrochloride;

(2-ethylindolizin-3-yl)(4-{4-[ethyl(propyl)amino]butyl}phenyl)methanone oxalate;

(4-{4-[ethyl(propyl)amino]butyl}phenyl)(2-propylindolizin-3-yl)methanone hydrochloride;

(2-butylindolizin-3-yl)(4-{3-[butyl(propyl)amino]propyl}phenyl)methanone oxalate;

(4-{3-[butyl(ethyl)amino]propyl}phenyl)(2-butylindolizin-3-yl)methanone oxalate;

(2-butylindolizin-3-yl)(4-{3-[(cyclopropylmethyl)(propyl)amino]propyl}phenyl)methanone hydrochloride;

{4-[4-(propylamino)butyl]phenyl}(2-propylindolizin-3-yl)methanone hydrochloride;

(2-butylindolizin-3-yl){4-[3-(propylamino)propyl]phenyl}methanone hydrochloride;

(2-butylindolizin-3-yl){4-[3-(dimethylamino)propyl]phenyl}methanone hydrochloride;

(2-butyl indolizin-3-yl)(4-{3-[(3R,5S)-3,5-dimethylpiperazin-1-yl]propyl}phenyl)methanone hydrochloride;

(2-butyl indolizin-3-yl)(4-{3-[(3R,5S)-3,4,5-trimethylpiperazin-1-yl]propyl}phenyl)methanone hydrochloride;

(4-{3-[bis(2-methoxyethyl)amino]propyl}phenyl)(2-butylindolizin-3-yl)methanone oxalate;

(2-butylindolizin-3-yl)[4-(3-piperidin-1-ylpropyl)phenyl]methanone oxalate;

(2-butyl-6-methylindolizin-3-yl){4-[3-(dipropylamino)propyl]phenyl}methanone hydrochloride;

(2-butyl-6-ethylindolizin-3-yl){4-[3-(dipropylamino)propyl]phenyl}methanone hydrochloride;

(2-butyl-6-methylindolizin-3-yl)(4-{3-[ethyl(propyl)amino]propyl}phenyl)methanone hydrochloride; and

(2-butyl-6-ethylindolizin-3-yl)(4-{3-[ethyl(propyl)amino]propyl}phenyl)methanone hydrochloride.

11. A method for preparing compounds of formula (I) according to claim 1 , said method comprising the step of reacting an amine H—Am with a compound of formula (II):

in which Y represents a halogen atom and the other substituents are as defined in claim 1 .

12. A method for preparing a compound of formula (II) according to claim 11 , said method comprising the step of reacting a compound of formula (III):

with a compound represented by formula (IV):

13. A compound of formula (I) according to claim 1 , for use as a drug.

14. A composition comprising a compound of formula (I) of claim 1 .

15. A pharmaceutical composition comprising, at least one compound of formula (I) according to claim 1 , or a pharmaceutically acceptable salt thereof, in combination with a pharmaceutical vehicle or an appropriate excipient.