1,2,4-SUBSTITUTED PIPERIDINES AND A METHOD OF THEIR SYNTHESIS, INTERMEDIUM COMPOUNDS OF PIPERIDONE AND A METHOD OF THEIR SYNTHESIS, PHARMACEUTICAL COMPOSITION BASED ON NEW COMPOUNDS Russian patent published in 1998 - IPC

FIELD: organic chemistry. SUBSTANCE: invention relates to new 1,2,4-substituted piperidines of the formula (I) where R₁ free phenyl- or diphenyl-C₁-C₄-alkyl or that substituted with halogen and/or trifluoromethyl; 9-fluorenyl, pyridyl-C₁-C₄-alkyl; quinolyl-C₁-C₄-alkyl; 5-chloro-2-(1H-1,2,4-triazolyl-1-yl)-phenoxy-C₁-C₄-alkyl; free benzoyl or that substituted with C₁-C₄-alkyl, C₁-C₄-alkoxyl, hydroxyl, halogen, trifluoromethyl, di-C₁-C₄-alkylamino-group and/or cyano-group; naphthoyl; 2-fluorenoyl; phenyl- or diphenyl-C₂-C₄-alkanoyl; naphthyl-C₂-C₄-alkanoyl; dimethylcyclohexanoyl; quinolylcarbonyl; pyridyl-C₂-C₄-alkanoyl; benzylhydroxycarbonyl; free phenylalanyl or phenylcarbamoyl or that substituted with acetyl or 4-carboxamidobutyroyl; 2,3,4,9-tetrahydro-1H-pyrido-[3,4-b]-indole-3-yl-carbonyl; R₂ - free phenyl or naphthyl or that substituted with halogen; R₃ - hydrogen, C₁-C₄-alkyl, cyclohexyl, phenylcarbamoyl or 3-aminocarbonylpropionyl; R₄ can be substituted if necessary with C₁-C₄-alkyl or C₁-C₄-alkoxyl, phenyl, naphthyl, benzyl, pyridyl that can be C-substituted if necessary with C₁-C₄-alkoxyl or indolyl N-substituted with C₁-C₄-alkanoyl; quinolyl; benzofuranyl; benzthiophenyl substituted if necessary with C₁-C₄-alkyl; dihydrobenzopyranyl or anilino-group; X - simple bond, methylene, hydroxymethylene or carbonyl; X - simple bond; X - simple bond, methylene, ethylene, benzylidene or carbonyl or their salts. Compounds of the formula (I) show antagonistic effect with respect to substance P and are the base of pharmaceutical composition exhibiting the indicated effect. Invention relates to also intermedium derivatives of piperidone of the formula (X) and their acid-additive salts where R₁ means if necessary benzoyl, naphthoyl, 9-fluorenyl substituted with C₁-C₄-alkyl, C₁-C₄-alkoxyl, hydroxyl, halogen, trifluoromethyl, di-C₁-C₄-alkylamino and/or cyano-group; quinolylcarbonyl; R₂ - free phenyl or naphthyl or that substituted with halogen; X₁ - hydroxymethylene. Compounds of the formula (I) where X means carbonyl are synthesized by interaction of amines of the formula (II) where R₁,R₂,R₃,X₁ and X₂ have the above indicated values with acids of the formula (IV) HOωR₄ (IV) where R₄ means the above indicated values, or their reactive derivatives. Compounds of the formula (I) where R₃ means hydrogen are synthesized by removal of protective group in compounds of the formula (IX) . Intermedium compounds of the formula (X) are synthesized by interaction of compounds of the formula (Xa) with P-residue incorporating compound. EFFECT: improved method of synthesis of new compounds. 104 cl, 1 tbl