PL438131A1 - Derivatives of 5-substituted-3-(1-alkilaryl-1,2,3,6-tetrahydropyridin-4-yl)-1H-indole and 5-substituted-3-(1-alkil-1,2,3,6-tetrahydropyridin-4-yl)-1H-indole, the method of their preparation and their application - Google Patents

Abstract

The subject of the invention are 5-substituted-3-(1-arylaalkyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-indole derivatives of the general formula 1, where R₁ is a substituent phenylethyl and R₂ is methoxy or R₁ is 4-methoxylenylethyl and R₂ is hydrogen or methoxy or ethoxy or R₁ is 4-fluorophenylethyl and R₂ is hydrogen or methoxy or ethoxy or R₁ is propylphenyl and R< sub>2</sub> means methoxy or ethoxy or R₁ means butylphenyl and R₂ means methoxy or ethoxy or R_{1< /sub> means (2-oxo-1H-benzo[b]oxin-3-yl)methyl and R₂ means hydrogen or methoxy or ethoxy and 5-substituted derivatives ne-3-(1-alkyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-indole of the general formula 1, where R₁ is a 2-methylpropyl substituent and R< sub>2} is hydrogen or methoxy or ethoxy or R₁ is isopropyl and R₂ is methoxy or ethoxy. The compounds of the invention are prepared by reacting 5-substituted indoles with 1-alkylaryl- or 1-alkyl-substituted piperidin-4-one derivatives in methanol in the presence of potassium hydroxide. The reaction is carried out for 18 hours at the reflux temperature of the solvent. The reaction mixture is allowed to crystallize freely or is cooled and, on cooling, a precipitate of the product is obtained. The reaction product is purified by washing with water, methanol, ether and recrystallized from a suitable solvent. preferably methanol or DMF, or purified by chromatographic methods, preferably by column chromatography (silica gel, gradient 2-5% anhydrous NH₃ in MeOH/DCM). Compounds of the invention which are multitarget ligands of monoamines, in particular the dopamine D₂ and serotonin 5-HT_1A and 5-HT_2A receptors, for use in in the treatment of mental illnesses, in particular schizophrenia, bipolar disorder and depression.