Patent GB-878683-A (GB)
Title: Improvements in or relating to iminodibenzyl derivatives
IPC: C07D405/12
Filed: 1959-06-18
Abstract: The invention comprises compounds of the formula <FORM:0878683/IV (b)/1> where A represents a divalent straight or branched saturated C2-4 aliphatic hydrocarbon group with at least two carbon atoms between the nitrogen atoms to which A is attached, X represents a hydrogen or halogen atom, n represents 1 or 2, and R represents a hydrogen atom or a C1-4 acyl group or a carbamoyl group which may be N-mono- or di-C1-4 alkyl substituted, and one or more of the carbon atoms of the piperazine nucleus may carry a C1-4 alkyl group; and their acid addition and quaternary ammonium salts; and the preparation thereof (1) by reacting a compound of the formula <FORM:0878683/IV (b)/2> with a compound of the formula <FORM:0878683/IV (b)/3> wherein one of the groups V and W represents a hydrogen atom and the other a group -A.B where B represents the acid residue of a reactive ester group, or (2) by reacting a compound of the formula <FORM:0878683/IV (b)/4> with a reactive ester of the formula B-(CH2CH2O) or (3), in the case where R represents an acyl group, by appropriate acylation or (4) where R represents a carbamoyl or N-substituted carbamoyl group, by treating the corresponding compound wherein R is a hydroxy group by known methods for the conversion of a hydroxy group to a urethane group, e.g. by the action of isocyanic acid, an alkyl isocyanate, a carbamyl halide, phosgene followed by ammonia or an amine, or an N-bromoamide.  The compounds may also be prepared by decarboxylation of a corresponding N N-piperazinoalkanoyl-iminodibenzyl compound by heating.  The compounds are used pharmaceytically (see Group VI). 5-(3-Chloropropyl) iminodibenzyl used as a starting material is made by the action of thionyl chloride on 5-(3-hydroxypropyl) iminodibenzyl.  5-(toluene-psulphonyloxyalkyl) iminodibenzyls, i.e. the 5-o -toluenesulphonyloxy-ethyl-, -propyl-, -butyl- and -2-methylpropyl-, iminodibenzyls, 5-(b - toluenesulphonyloxy-propyl) iminodibenzyl and 5-o -toluenesulphonyloxy-ethyl- and-propyl-, 3 : 7-dichloroiminodibenzyls are prepared by the action of toluene-p-sulphonyl chloride on the corresponding hydroxy compounds. 5-Hydroxyalkyliminodibenzyls used as intermediates in the preparation of the above haloalkyl and toluenesulphonyloxyalkyl compounds are made by reacting a haloalkoxy-tetrahydropyran with the iminodibenzyl and hydrolysing the resulting 5-tetrahydropyranyloxyalkyl-iminodibenzyl.ALSO:Pharmaceutical preparations for oral, rectal or parenteral administration having relaxant, anti-Parkinsonian, anti-emetic and anti-histaminic activity comprise compounds of the formula <FORM:0878683/VI/1> and acid addition and quaternary salts thereof, wherein A is a saturated, straight or branched aliphatic hydrocarbon group of 2-4 carbon atoms, with at least two carbon atoms between the iminodibenzyl and piperazine nitrogen atoms, X is hydrogen or halogen, n is 1 or 2, R is hydrogen or a C1-4 acyl group or a carbamoyl or mono- or di-C1-4 alkyl carbamoyl group (see Group IV (b)) and a pharmaceutical carrier.  The preparations may suitably take the form of tablets, pills, powders, granules, emulsions, solutions, suspensions, syrups, elixirs and capsules containing conventional excipients for oral administration, or aqueous or non-aqueous solutions, suspensions or emulsions, which may be sterilized by sterilizing agents, filtration, heat or radiation, for parenteral administration.  Examples describe preparations of 5 - (3 - 41 - b  - hydroxyethyl - 11 - piperazinylpropyl) iminodibenzyl (a) in tablets containing starch, silica and magnesium stearate; (b) in a sterile aqueous solution containing methane-sulphonic acid, sodium sulphite, ascorbic acid and sodium chloride.