GB1013908A - Improvements in and relating to n-substituted 2,3-polymethyleneindoles - Google Patents

Abstract

The invention comprises compounds of general formula <FORM:1013908/C2/1> where X is hydrogen, halogen, nitro, amino or methyl, R is hydrogen or phenyl, R1 is hydrogen or methyl, n is 5-13, m is 0-4, and Am is amino, lower (i.e. 1-6 C) alkylamino, di-(lower) alkylamino, hydroxy (lower) alkylamino, di-(hydroxy-lower alkyl) amino, piperidino, morpholino, pyrrolidino, piperazino, N-lower alkyl-piperazino or N-(hydroxy-lower alkyl)-piperazino: and their salts with pharmaceutically acceptable acids: and their preparation by reacting a 2,3-polymethyleneindole having the formula <FORM:1013908/C2/2> in which X1 is hydrogen, halogen, nitro or methyl, and n is 5-13, with a reagent capable of substituting on the indole nitrogen atom a substituent having the formula -W-CHR1(CH2)mY where W is methylene, benzylidene, or -C : O.O-, R1 is hydrogen or methyl, m is 0-4, and Y is a carboxylic acid radical, a carboxylic ester radical, a nitrile radical, a hydroxy radical, chlorine, bromine, iodine, an alkylsulfonoxy radical, an arylsulfonoxy radical, or as defined for Am, heating where W is -COO and, where Y is other than a radical Am, further reacting by amidating in the case where Y is halogen, alkylsulfonoxy or arylsulfonoxy; reducing followed by halogenation of the hydroxyl group produced thereby and amidating the halogen group, or amidating and reducing where Y is a carboxylic acid radical or a carboxylic acid ester; halogenating and amidating where Y is hydroxyl, and where Y is nitrile reducing or forming the corresponding carboalkoxyalkyl compound and then reducing, halogenating and amidating or amidating and reducing to convert these radicals to a radical Am, and, if desired, when the product is a primary or secondary amine further subjecting the same to N-alkylation or N-hydroxy-alkylation and, if desired, where X1 is nitro reducing to the corresponding 5-amino compound. 1 - (2 - Cyanoethyl) - 2,3 - pentamethyleneindole is prepared from the N-unsubstituted compound and acrylonitrile. Treatment with ethanol and hydrogen chloride yields the 1-(2-carboethoxyethyl)-compound and this with lithium aluminium hydride the 1-(3-hydroxypropyl)-compound; reaction with hydrogen bromide gives 1-(3-bromopropyl) - 2,3 - pentamethyleneindole. 1 - (2 - Carbomethoxyethyl) - 2,3 - hexamethyleneindole is prepared by reacting the cyanoethyl compound with methanol; reaction with methylamine gives 1-(2-carbomethamidoethyl)-2,3-hexamethyleneindole. 3 - Dimethylaminopropyl ester of 2,3-pentamethyleneindole-1-carboxylic acid ester is prepared by reacting the N-unsubstituted compound with phosgene to give the 1-carbonyl chloride then reacted with the amino-alcohol. 2,3-Pentamethylindoles having 5-fluoro, chloro, nitro, and methyl substituents are prepared from p-substituted phenylhydrazines and cycloheptanone; 2,3-octamethyleneindole is obtained from phenylhydrazine and cyclodecanone.ALSO:Therapeutic compositions contain compounds of general formula <FORM:1013908/A5-A6/1> where X is hydrogen, halogen, nitro, amino or methyl, R is hydrogen or phenyl, R1 is hydrogen or methyl, n is 5-13, m is 0-4, and Am is amino, lower (i.e. 1-6C) alkylamino, di(lower)alkylamino, hydroxy(lower)alkylamino, di(hydroxy-loweralkyl) amino, piperidino, morpholino, pyrrolidino, piperazino, N-lower-alkyl-piperazino or N-(hydroxy-lower-alkyl)-piperazino, and their salts with pharmaceutically acceptable acids, together with pharmaceutically acceptable carriers. Oral and parenteral administration one mentioned. The compounds are antidepressante, antihistamines, ataractics, tranquilisers and analgesics and also act as appetite inhibitors, in which case amphetamine or other phenylethylamine derivatives may be incorporated.