Patent EA-004508-B1 (EA)
Title: Phenyl-andpyridyl-tetrahydro-pyridines having tnf inhibiting activity
Inventor: BARONI MARCO
IPC: B29D35/06
Filed: 2000-10-19
Abstract: 1. A compound of formula (I) wherein: X represents N or CH; R1 represents a hydrogen or halogen atom or a CF3 group; R2 and R3 independently represent a hydrogen atom or a methyl group; n is 0 or 1; A represents a group of formula (a) or (b) wherein: R4 represents a hydrogen or halogen atom, a (C1-C4) alkyl group, a CF3 group, an amino, mono(C1-C4)alkylamino, di(C1-C4)alkylamino; R5 represents a hydrogen or halogen atom, a (C1-C4)alkoxy group, a (C1-C4)alkyl group or a CF3 group; R6 represents a hydrogen atom, a (C1-C4)alkyl group or a (C1-C4)alkoxy group; and their salts or solvates. 2. The compound of claim 1, wherein n is zero. 3. The compound of claim 1 or 2, wherein R2 and R3 represent hydrogen. 4. The compound of any one of claims 1 to 3, wherein R1 represents CF3. 5. The compound of any one of claims 1 to 3, wherein R1 represents a fluorine atom. 6. The compound of any one of claims 1 to 3, wherein X represents CH, and R1 is in the position of 3 benzene. 7. The compound of any one of claims 1 to 3, wherein X represents CH, and R1 is in the position of 2 benzene. 8. The compound of any one of claims 1 to 3, wherein X represents a nitrogen atom and pyridine is substituted in positions 2 and 6. 9. The compound of any one of claims 1 to 8, wherein selected from mono-N-oxide and bis-N-oxide derivatives thereof. 10. The compound of claim 1, wherein selected from 7-(2-(4-(3-trifluoromethyl-phenyl)-1,2,3,6-tetrahydro-1-pyridyl) ethyl) isoquinoline, mono-N-oxide and bis-N-oxide derivatives thereof and salts or solvates thereof. 11. A method for preparing a compound of claim 1, wherein a condensation/reduction reaction is carried out between the compound of formula (VI): wherein X and R1 are as defined in claim 1, and aldehyde of formula (VII): wherein R2, R3 and A are as defined in claim 1, and the compound of formula (I) is isolated and optionally transformed in a salt or solvate thereof or N-oxide thereof. 12. A method for preparing a compound of claim 1, wherein a) compound of formula (II) wherein X and R1 are as defined in claim 1, reacts with a functional acid derivative of formula (III): wherein R2, R3, n and A are as defined in claim 1, b) a carbonyl group, thus obtained, a compound of formula (IV) is reduced c) thus obtained an intermediate compound piperidinol of formula (V): is dehydrated, d) thus obtained a compound of formula (I) is isolated and optionally transformed in a salt or solvate thereof or N-oxide thereof. 13. A compound of formula (V): X represents N or CH; R1 represents a hydrogen or halogen atom or a CF3 group; R2 and R3 independently represent a hydrogen atom or a methyl group; n is 0 or 1; A represents a group of formula (a) or (b) wherein: R4 represents a hydrogen or halogen atom, a (C1-C4) alkyl group, a CF3 group, an amino, mono(C1-C4)alkylamino, di(C1-C4)alkylamino; R5 represents a hydrogen or halogen atom, a (C1-C4)alkoxy group, a (C1-C4)alkyl group or a CF3 group; R6 represents a hydrogen atom, a (C1-C4)alkyl group or a (C1-C4)alkoxy group; and their salts or solvates. 14. A compound of formula (VI): X represents N or CH; R1 represents a hydrogen or halogen atom or a CF3 group; R2 and R3 independently represent a hydrogen atom or a methyl group; n is 0 or 1; A represents a group of formula (a) or (b) wherein: R4 represents a hydrogen or halogen atom, a (C1-C4) alkyl group, a CF3 group, an amino, mono(C1-C4)alkylamino, di(C1-C4)alkylamino; R5 represents a hydrogen or halogen atom, a (C1-C4)alkoxy group, a (C1-C4)alkyl group or a CF3 group; R6 represents a hydrogen atom, a (C1-C4)alkyl group or a (C1-C4)alkoxy group; and their salts or solvates. 15. A pharmaceutical composition comprising a compound of formula (I) of claims 1 to 10 as an active ingredient or a pharmaceutically acceptable salt or solvate thereof. 16. The composition of claim 15, wherein comprises between 0.001 and 100 mg of active ingredient. 17. Use a compound of formula (I) of claims 1 to 10 or a pharmaceutically acceptable salt or solvate thereof for preparing analgetic medicaments and/or medicaments for treating diseases associated with immune and inflammatory disorders.