Derivatives of
View Patent ↗The invention relates to compositions comprising a compound having general formula (I): Wherein R, R1, R2, X and n are as described herein. Also disclosed and claimed in certain of the embodiments herein are the methods of preparation of compound of formula (I) and its use in therapeutics.
1. A pharmaceutical composition comprising a compound of the formula (I) or a pharmaceutically acceptable salt, a stereoisomer, a hydrate or a solvate thereof in combination with at least one pharmaceutically acceptable excipient:
wherein
R represents a hydrogen atom;
n represents 1;
X represents a group of formula CH;
R 1 represents either a phenyl or naphthyl group optionally substituted with one or more substituents chosen from halogen atoms, linear or branched (C 1 -C 6 )alkyl, hydroxyl and (C 1 -C 6 )alkoxy groups, the trifluoromethyl group, or a cyclohexyl group, or a heteroaryl group chosen from thienyl, pyridinyl, oxazolyl, furanyl, thiazolyl, quinolinyl, and isoquinolinyl groups;
R 2 represents either a hydrogen atom, or one or more substituents chosen from halogen atoms, trifluoromethyl, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, thienyl, phenyloxy, hydroxyl, mercapto,thio(C 1 -C 6 )alkyl and cyano group or a group of formula —NR 4 R 5 , SO 2 NR 4 R 5 , —SO 2 —(C 1 -C 6 ) alkyl,—SO 2 -phenyl, —CONR 4 R 5 , —COOR 7 , —CO—(C 1 -C 6 )alkyl, —CO-phenyl, —NHCOR 8 , —NHSO 2 —(C 1 -C 6 )-alkyl, —NHSO 2 -phenyl and —NHSO 2 NR 4 R 5 or a group of formula —OCF 2 O— attached at the 2- and 3-positions of the phenyl group;
the groups (C 1 -C 6 )alkyl, —SO— 2 —(C 1 -C 6 )alkoxy, —CO—(C 1 -C 6 )alkyl and —NHSO 2 —(C 1 -C 6 ) alkyl being optionally substituted with one or more groups R 3 ;
the groups phenyl, —SO 2 -phenyl, —CO-phenyl and —NHSO 2 -phenyl being optionally substituted with a group R 6 ;
R 3 represents a halogen atom, or a phenyl, (C 1 -C 6 )alkoxy or —NR 4 R 5 group;
R 4 and R 5 represent, independently of each other, a hydrogen atom or a (C 1 -C 6 )alkyl group or R 4 and R 5 form with the nitrogen atom bearing them a pyrrolidine ring, a piperidine ring or a morpholine ring;
R 6 represents a hydrogen atom, a halogen atom, a trifluoromethyl group, a cyano group, a hydroxyl group, a mercapto group, a (C 1 -C 6 )alkyl or (C 1 -C 6 )alkoxy group;
R 7 represents a hydrogen atom or a (C 1 -C 6 )alkyl group optionally substituted with one or more groups R 3 , or a phenyl group optionally substituted with a group R 6 ;
R 8 represents a (C 1 -C 6 )alkyl group optionally substituted with one or more groups R 3 , or a (C 1 -C 6 )alkoxy group, or a phenyl group optionally substituted with a group R 6 ; and
said compound in the form of a free base or an addition salt with an acid, stereoisomer thereof.
2. The composition according to claim 1 , wherein said compound is in the threo configuration.
3. The composition according to claim 1 , wherein R 1 represents an optionally substituted phenyl group.
4. The composition according to claim 2 , wherein R 1 represents an optionally substituted phenyl group.
5. The composition according to claim 1 , wherein said compound is selected from the group consisting of:
threo-2-chloro-N-[(1-azabicyclo[2.2.2]oct-2-yl)phenylmethyl]-3-trifluoromethylbenzamide hydrochloride 1:1;
threo-2,6-dichloro-N-[(1-azabicyclo[2.2.2]oct-2-yl)phenylmethyl]-3-trifluoromethylbenzamide hydrochloride 1:1;
2,6-dichloro-N-[(1S)-[(2S)(1-azabicyclo[2.2.2]oct-2-yl)phenylmethyl]-3-(trifluoromethyl) benzamide hydrochloride 1:1;
threo-N-[1-Azabicyclo[2.2.2]oct-2-yl(4-fluorophenyl)methyl]-2,6-dichloro-3-(trifluoromethyl)benzamide hydrochloride 1:1; and
said compound in the form of a free base or an addition salt with an acid thereof.
6. A pharmaceutical composition comprising 2-chloro-N—(8α,9S)cinchonan-9-yl)-3-trifluoromethylbenzamide hydrochloride 2:1 or a pharmaceutically acceptable salt thereof in combination with at least one pharmaceutically acceptable excipient.