Compositions containing new indole derivatives and their use in pharmacology

#The present invention relates to new compositions containing derivatives of indole which compositions are useful in the treatment of pathological conditions caused by disturbances in the serotonin systems. In particular, these compounds may be used as psychotropic drugs, and in particular as anti-depressants in mammels.

#They may be represented by the formula ##STR2## wherein R is a hydrogen atom, an alkyl group having from 1 to 4 carbon atoms, or an aralkyl group of which the alkyl has 1 or 2 carbon atoms,

#X is a hydrogen atom, alkyl, alkoxy or alkylthio containing from 1 to 4 carbon atoms, a halogen atom such as chlorine, fluorine, bromine, a trifluoromethyl, nitro, hydroxy or amino group, the latter possibly being substituted by one or two alkyl groups, by an acyl group or by an alkyl-sulfonyl group; and

#The examples set forth below are illustrative of the invention:

#An iodine crystal is added to a suspension of 7.1 gm of magnesium turnings in 90 ml of anhydrous ether. This is followed by heating under reflux and slow addition of a solution of 42 gm of methyl iodide in 90 ml of anhydrous ether. Refluxing is maintained until the magnesium disappears. The resulting solution is cooled to 20.degree. C. There is then added to this solution, 15.7 gm of a solution of indole in 90 ml of anhydrous ether. The addition takes place over a period of 10 minutes. The ensuing exothermic reaction brings the ether solution to the refluxing temperature and refluxing conditions are maintained by heating for 1 hour. The solution obtained in this manner is then cooled to a temperature between 0 and 5.degree. C. To this solution there is then gradually added a benzene solution of the chloride of benzyloxycarbonyl -1 piperidyl-4 acetic acid. The latter is obtained by reacting 31.8 gm of thionyl chloride with 37.1 gm of benzyloxycarbonyl-1 piperidyl-4 acetic acid in accordance with the procedure shown in I. de Graw, J. Heterochem. 3, 90, 1966. As a result of the reaction with the acid chloride, the oily product salts out and then crystallizes. The suspension is shaken for 15 hours at ambient temperature. Then 30 ml of an aqueous solution of 2 N hydrochloric acid are added. Dissolution takes place at once.

#The organic phase is decanted, dried on magnesium sulfate and then evaporated. The residual oil (54.3 gm) is dissolved in 500 ml of a 5 N solution of anhydrous hydrochloric acid in ethanol. The solution so obtained is heated under reflux for two hours, and then evaporated under partial vacuum. The residue is dissolved in 200 ml of boiling isopropanol and the solution is cooled to 0.degree. C.