Patent GB-1154976-A (GB)
Title: N-Phenyl Indoline Derivatives
Inventor: CANAS-RODRIGUEZ ANTONIO
IPC: A61K31/00
Filed: 1967-02-21
Abstract: 1,154,976. N-Phenyl indoline derivatives. PFIZER Ltd. 19 Feb., 1968 [21 Feb., 1967], No. 8172/67. Heading C2C. Novel compounds of the general formula wherein R<SP>1</SP> and R<SP>2</SP> each represent a hydrogen atom, a lower alkyl group, a benzyl group or together with the nitrogen atom to which they are attached form a saturated ring which, if it contains a further nitrogen atom, may be substituted at such nitrogen atom with a lower alkyl or hydroxalkyl group or a benzyl group; R<SP>3</SP> represents a lower alkyl group, a phenyl group or a benzyl group; C n H 2n  represents a bivalent saturated lower aliphatic hydrocarbon group in which n is at least 2 and in which the free valences are located on different carbon atoms; X represents either an oxygen atom or two hydrogen atoms; and any benzene ring in the structural formula or in R<SP>1</SP>, R<SP>2</SP> or R<SP>3</SP> may be substituted with one or more halogen atoms, lower alkyl or alkoxy groups, trifluoromethyl groups, nitro groups, hydroxyl groups or sulphamoyl or N-substituted sulphamoyl groups; (the term " lower ", used to qualify the terms alkyl " hydroxyalkyl " or " aliphatic ", indicates "containing not more than 8 carbon atoms in a straight or branched chain ") and the pharmaceutically acceptable acid addition salts of such compounds, with the exception of the single chemical compound in which R<SP>1</SP>, R<SP>2</SP> and R<SP>3</SP> are each methyl, C n H 2n  is ethylene, X is an oxygen atom and the benzene rings are unsubstituted, are prepared by one of the following methods: (a) a compound of Formula II with an amine of formula Hal-(C n H 2n )NR<SP>1</SP>R<SP>2</SP> to give a compound of the above formula wherein X is O; (b) by reduction of a compound of Formula IV (c) a compound of the Formula VI is condensed with an amine of the formula HNR<SP>1</SP>R<SP>2</SP>; (d) compounds in which neither R<SP>1</SP> nor R<SP>2</SP> is hydrogen may be converted into compounds in which R<SP>2</SP> is hydrogen; (e) compounds of Formula I above in which at least one of R<SP>1</SP> and R<SP>2</SP> is hydrogen may be converted into compounds in which R<SP>1</SP> and/or R<SP>2</SP> is alkyl or benzyl by alkylation or benzylation of the aforementioned amino group; (f) compounds in which X is an oxygen atom may be reduced with, for example, lithium aluminium hydride or diborane to yield the corresponding indoline compound. Indolinones of Formula II above may be prepared by cyclization of the corresponding alpha-chloro diphenyl amide. Nitriles of Formula IV above are prepared by reaction of a compound of Formula II above with a halide of Formula Hal-(C n-1 H 2n-2 )CN. Halides of Formula VI above are prepared by reaction of a compound of Formula II above with a di-bromo alkane. 5-Substituted compounds of Formula II above are prepared by reaction of bromine or an acid chloride within the presence of a Lewis acid to give the substituted compounds. Pharmaceutical compositions having antidepressant type activities and being in conventional forms for oral or parenteral administration comprise an above novel compound and a pharmaceutical carrier therefor.