Urea derivatives of tropane, their preparation and their therapeutic application

1. A compound of formula (I)

wherein:

X is a carbon;

 is a single bond or a double bond;

R 1a , R 1b , R 1c , R 1d , R 2a and R 2b are hydrogen,

R 3 is hydrogen;

R 4 is:

hydrogen or (C 1 -C 5 )alkyl,

(C 3 -C 6 )cycloalkyl,

heterocyclyl,

(C 5 -C 10 ) monocyclic or bicyclic aryl, or

(C 2 -C 9 ) monocyclic or bicyclic heteroaryl,

wherein the aryl or heteroaryl group is optionally substituted with 1 to 4 substituents chosen from the group consisting of halogen, (C 1 -C 5 )alkyl, (C 1 -C 5 )alkoxy, (C 1 -C 5 )haloalkyl, hydroxyl, hydroxy(C 1 -C 5 )alkyl, (C 1 -C 5 )alkoxy(C 1 -C 5 )alkyl, cyano, optionally substituted phenyl, optionally substituted benzyl, —COOR 5 , —NR 6 R 7 , R 5 OOC—(C 1 -C 5 )alkyl, NR 6 R 7 —(C 1 -C 5 )alkyl, —CONR 6 R 7 , NR 6 R 7 —CO—(C 1 -C 5 )alkyl, —SO 2 NR 6 R 7 , and —NR 6 —COR 5 ;

R 5 is hydrogen, (C 1 -C 5 )alkyl or (C 3 -C 6 )cycloalkyl; and

R 6 and R 7 , are independently hydrogen, (C 1 -C 5 )alkyl, (C 3 -C 6 )cycloalkyl, (C 1 -C 5 )alkylcarbonyl, hydroxymethyl(C 1 -C 5 )alkyl, (C 1 -C 5 )alkoxymethyl(C 1 -C 5 )alkyl, aryl or —SO 2 —R 5 , or

R 6 and R 7 , taken together with the nitrogen atom to which they are attached, form an optionally substituted heterocyclyl;

or a salt thereof, or an enantiomer or diastereoisomer thereof.

2. The compound according to claim 1 , wherein:

R 4 is pyridyl, phenyl, or pyrazolyl;

or a salt, thereof, or an enantiomer or diastereoisomer thereof.

3. The compound according to claim 1 , wherein:

 is a double bond; and

R 4 is phenyl or pyridyl;

or a salt thereof, or an enantiomer or diastereoisomer thereof.

4. The compound according to claim 1 , wherein:

 is a single bond; and

R 4 is phenyl, pyridyl or pyrazolyl;

or a salt thereof, or an enantiomer or diastereoisomer thereof.

5. A process for preparing the compound according to claim 1 , comprising reacting a compound of formula (IV):

wherein:

R 1a , R 1b , R 1c , R 1d , R 2a , R 2b , p and r are as defined in claim 1 , and Lg is a leaving group;

with a compound of formula (V)

wherein:

R 3 and R 4 are as defined in claim 1 .

6. A pharmaceutical composition, comprising the compound according to claim 1 , or an enantiomer or diastereoisomer thereof, or a pharmaceutically acceptable salt thereof, in combination with at least one pharmaceutically acceptable excipient.

7. A pharmaceutical composition, comprising the compound according to claim 2 , or an enantiomer or diastereoisomer thereof, or a pharmaceutically acceptable salt thereof, in combination with at least one pharmaceutically acceptable excipient.

8. A pharmaceutical composition, comprising the compound according to claim 3 , or an enantiomer or diastereoisomer thereof, or a pharmaceutically acceptable salt thereof, in combination with at least one pharmaceutically acceptable excipient.

9. A pharmaceutical composition, comprising the compound according to claim 4 , or an enantiomer or diastereoisomer thereof, or a pharmaceutically acceptable salt thereof, in combination with at least one pharmaceutically acceptable excipient.