Patent GB-788447-A (GB)
Title: Diuretic compositions
Inventor: CROWTHER ALBERT FREDERICK
IPC: A61K31/00
Filed: 1954-10-22
Abstract: The invention comprises compounds of the formula: <FORM:0788447/IV (b)/1> wherein X stands for hydrogen or halogen and Y stands for halogen and R stands for an alkyl radical of 2 to 4 carbon atoms, provided that when Y stands for chlorine and R stands for an isopropyl radical X stands for halogen.  Such compounds are obtained by the reaction of the corresponding N1-halogenophenyl-N5-alkylbiguanide, optionally in the form of a salt thereof, for example the hydrochloride, with formic acid or a salt or ester or other methenylating derivative thereof, for example formamide, a dialkylformamide or a diarylformamidine.  The N1-halogenophenyl - N5 - alkylbiguanide may be generated in situ by synthesis from, for example, a halogenoaniline salt and an alkyldicyandiamide.  When the N1-halogenophenyl-N5-alkylbiguanide is used in the form of a salt, the reaction with formic acid is preferably effected in the presence of a salt of formic or acetic acid.  In examples: (1) a mixture of N1 - 2 : 4 - dichlorophenyl - N5 - isopropylbiguanide hydrochloride and sodium formate in formic acid is refluxed to give 2-(2 : 4-dichloroanilino) - 4 - isopropylamino - 1 : 3 : 5 - triazine.  Analogously prepared are (2) 2-(2 : 4-dichloroanilino) - 4 - ethylamino - 1 : 3 : 5 - triazine; (3) 2 - (2 : 4 - dichloroanilino) - 4 - n-propylamino - 1 : 3 : 5 - triazine; (4) 2 - (2 : 4-dichloroanilino) - 4 - n - butylamino - 1 : 3 : 5-triazine.  In Example (5) N1-p-chlorophenyl-N5-ethylbiguanide and ethyl formate are refluxed together in methanol to give 2-p-chloroanilino - 4 - ethylamino - 1 : 3 : 5 - triazine.  Similarly obtained are the 4-n-propylamino, 4-n-butylamino and 4-isobutylamino derivatives. Specification 676,024 is referred to.ALSO:A diuretic pharmaceutical composition comprises as active diuretic ingredient one or more triazine derivatives of the formula  <FORM:0788447/VI/1> wherein R stands for an alkyl radical of 2 to 4 carbon atoms, X stands for hydrogen or halogen and Y stands for halogen.  The compositions may be in the form of tablets or pills with excipients such as calcium carbonate or lactose, disintegrating agents such as maize starch, lubricating agents such as stearic acid or magnesium stearate and binding agents such as starch paste, gelatin solution or gum acacia.  Aqueous compositions of the triazine derivatives may contain dispersing agents such as sodium carboxymethylcellulose, wetting agents such as polyethyleneoxycetanols and preservatives such as a p-hydroxybenzoic acid and flavouring and colouring agents. Examples describe tablets comprising (6) 2-p-chloroanilino - 4 - isopropyl - 1 : 3 : 5 - triazine, maize starch, calcium carbonate and magnesium stearate; (7) 2-(2 : 4-dichloroanilino)-4-iso-propylamino-1 : 3 : 5-triazine with other ingredients as in (6); aqueous suspensions formed from (8) icing sugar, sodium carboxymethyl-cellulose, heptadecaethyleneoxycetanol, methyl p-hydroxybenzoate, raspberry flavouring agent dyestuff (Colour Index Number 179) and p-chloronilino - 4 - isopropylamino - 1 : 3 : 5-triazine (the mixture being ball-milled); (9) the same ingredients as in (8), except that 2-(2 : 4 - dichloroanilino) - 4 - isopropylaminotrizine is the active ingredient.  Specification 676,024, [Group IV (b)], is referred to.