Patent GB-837965-A (GB)
Title: Improvements in or relating to amines and to processes for their preparation
Inventor: ASHLEY JULIUS NICHOLSON
IPC: A61K31/135
Filed: 1957-10-18
Abstract: The invention comprises compounds of the formula <FORM:0837965/IV (b)/1> and acid addition salts thereof, wherein R1 and R2 are hydrogen, C1-6 alkyl, or hydroxyalkyl (including polyhydroxyalkyl), B is a hydrocarbon chain of 2 or 3 carbon atoms, saturated or ethylenically unsaturated and optionally bearing lower alkyl substituents, R1 is a C1-4 alkyl or alkoxy group and R3 is hydrogen or a C1-4 alkyl or alkoxy, or primary, secondary or tertiary amino or nitro substituent, preferably in the p-position; and sodium formaldehyde-bisulphite derivatives of the primary amines of the above formula.  The compounds are prepared as described in the parent Specification by condensing a compound of the formula <FORM:0837965/IV (b)/2> with a compound <FORM:0837965/IV (b)/3> wherein X is a tertiary amino group NR1R2 or a group convertible to a primary, secondary or tertiary group NR1R2, M is hydrogen or an alkali-metal, B1 is the same as B or is a corresponding less saturated group, Y is the group R3 or an atom or group convertible thereto, Q is the radical of a reactive ester, e.g. methane-sulphonate or halogen and R11 the same as R1 or is a hydroxyl group; followed, if necessary, by conversion of the groups X, Y, B1 and R11 into NR1R2, R3, B and R1. The products are use in the treatment of bilharziasis.  Examples describe the preparation of a -(4-amino-2-methoxyphenoxy) - o  - phenyl - ethane, - propane and a -methylpropane (methanesulphonate) and a  - (4 - dimethylamino - 2 - methoxyphenoxy) - b -phenyl-ethane and a -(4-b -hydroxyethylamino-2 - methoxyphenoxy) - b  - phenyl - ethane (hydrobromide).  1 - (2 - Methoxy - 4 - nitrophenoxy) - 2 - phenyl-ethane, 3-phenylpropane and 3-phenyl-1-methyl-propane are made by treating potassium 2-methoxy-4-nitrophenoxide with the appropriate phenylalkyl bromide. 1 - (4 - Dimethylamino - 2 - methoxyphenoxy) - 2-phenylethane methiodide is made by the action of methyl iodide on the primary base.  1 - (4 - b  - Chloroethoxycarbonamido - 2 - methoxyphenoxy) - 2 - phenylethane is made by the action of 2-chloroethyl chloroformate on 1-(4-amino-2-methoxyphenoxy)-2-phenylethane.ALSO:Pharmaceutical preparations for the treatment of bilharziasis comprise compounds of the formula <FORM:0837965/VI/1> or acid addition salts thereof, wherein R1 and R2 are hydrogen, C1-6 alkyl or hydroxyalkyl (including polyhydroxyalkyl), B is a hydrocarbon chain of 2 or 3 carbon atoms, saturated or ethylenically unsaturated and optionally bearing lower alkyl substituents, R1 is a C1-4 alkyl or alkoxy group and R3 is hydrogen or a C1-4 alkyl or alkoxy group or a primary, secondary or tertiary amino or a nitro substituent, preferably in the p-position, or a formaldehyde-bisulphite addition product of a primary amine of the above formula, and a pharmaceutical carrier suitable for oral or parenteral administration.  The preparations suitably take the form of solutions, suspensions, syrups, elixirs, emulsions, powders or tablets.  Suitable excipients for tablets or compressed powders include starch, lactose, stearic acid, magnesium stearate or dextrin.