Patent GB-852083-A (GB)
Title: Aminophenyl ethers
Inventor: ASHLEY JULIUS NICHOLSON
IPC: A61K31/135
Filed: 1958-06-24
Abstract: The invention comprises aminophenoxy compounds of the formula : <FORM:0852083/IV(b)/1> and acid addition salts thereof, wherein R1 and R2 are hydrogen or lower alkyl, alkoxyalkyl or hydroxyalkyl (including polyhydroxyalkyl) groups of 1-4 carbon atoms, R3 is an alkyl or alkoxy group of 1-4 carbon atoms and R is a straight or branched chain, saturated or unsaturated, aliphatic hydrocarbon group of 3-12 carbon atoms.  Suitably R may be an n-hexyl, n-heptyl, n-octyl or n-decyl group, preferred products being 1-(4-amino-2-methoxyphenoxy)-n-heptane and n-octane.  The compounds are prepared by reacting a compound of the formula : <FORM:0852083/IV(b)/2> with a compound of the formula Z2Y wherein X is the group R1R2N or a group convertible thereto (e.g. acylamido, nitro, carbonamido, alkoxycarbonylamino and arylazo, convertible to primary amino; acylalkylamino and acylamido, convertible to secondary amino by hydrolysis and reduction respectively and quaternary ammonium and acylalkylamino groups convertible to tertiary amino by pyrolysis and reduction respectively), B is the group R2 or a group convertible thereto (e.g. a hydroxy group or a protected hydroxy group such as methoxymethoxy or benzyloxy), Z1 is a hydrogen atom or an alkali-metal ion, Z2 is the residue of a reactive ester (e.g. a halogen atom or the residue of an organic sulphonic ester) and Y is the group R or a group convertible thereto.  Compounds in which NR1R2 is a primary or secondary amino group can be converted to secondary or tertiary amino compounds by known methods, e.g. a primary amine may be reacted with an aldehyde or ketone and the condensate reduced to a secondary amine, Many typical products are exemplified. 1-Hydroxy-n-pent-4-ene p-toluenesulphonate is made by esterifying 1-hydroxy-n-pent-4-ene with p-toluenesulphonyl chloride. 4-Hydroxy-3-methoxyphenol trimethyl ammonium iodide is made by treating quaiacol with dimethyl sulphate and converting the product to the iodide by means of aqueous potassium iodide. 1-(4-Formamido-2-methoxyphenoxy)-n-octane is made by the action of formamide on 4-amino-2-methoxyphenoxy-n-octane.ALSO:Pharmaceutical preparations for the treatment of worm infections such as bilharziasis and fascioliasis, particularly liver flake in sheep and cattle comprise one or more compounds of the formula: <FORM:0852083/VI/1> or acid addition salts thereof, where R1 and R2 are hydrogen or alkyl, alkoxyalkyl, hydroxyalkyl or polyhydroxyalkyl groups of 1-4 carbon atoms, R3 is an alkyl or alkoxy group of 1-4 carbon atoms and R is a straight or branched chain, saturated or unsaturated aliphatic hydrocarbon groups of 3-12 carbon atoms (see Group IV(b)) and a pharmaceutical carrier.  The preparations may take the form of compositions for oral administration for example solid compositions such as tablets, pills, dispersible powders, capsules and granules, or liquid compositions such as emulsions, solutions, suspensions, syrups and elixirs which may contain such diluents as water and liquid paraffin, together with wetting and suspending agents and sweetening and flavouring agents.  Compositions for parenteral administration include sterile aqueous or non-aqueous solutions, suspensions or emulsions, suitable non-aqueous solvents or suspending media being propylene glycol, polyethylene glycol, vegetable oils such as olive oil and injectable organic esters such as ethyl oleate.  The preferred compounds are 1-(4-amino-2-methoxyphenoxy)-n-heptane, and 1-(4-amino-2-methoxyphenoxy)-noctane and their acid addition salts.