GB1149640A - Amino-halopteridines and pharmaceutical compositions containing them - Google Patents

Abstract

1,149,640. 2,4-Diaminopteridine compounds. MERCK & CO. Inc. 28 Sept., 1966 [4 Oct., 1965], No. 43401/66. Heading C2C. The invention comprises 2,4-diarnino-pteridines of the formula where Y is Cl, Br or I and X is H, Cl, Br, mercapto, hydroxy, C 1-6 aliphaticoxy, mononuclear-aryl-substituted C 1-6 aliphaticoxy, C 1-6 aliphaticthio, mononuclear-aryl-substituted C 1-6 aliphaticthio, C 1-6 aliphatic, mononuclear aryl, or mononuclear-aryl-substituted C 1-6 aliphatic, or an amino radical -N-(CH 2 ) n , where n is 4, 5 or 6 or where each of R and R<SP>1</SP>, which are the same or different, is H, C 1-6 alkoxy, C 1-6 alkyl, mononuclear aryl, or a substituted C 1-6 alkyl radical having one or more substituents taken from halogen, hydroxy, alkoxy, C 3-6 cycloalkyl, mononuclear aryl, (C 1-6 alkyl)-substituted mononuclear aryl, halogenated mononuclear aryl, amino, C 1-6 alkylamino, di(C 1-6 alkyl)amino and heterocyclics (e.g. furyl and pyridyl). The novel compounds (except those in which X is hydroxy or mercapto) are obtained by reaction of a 3- amino - 5 - X - 6 - halopyrazinonitrile with guanidine. Compounds of Formula I in which X is hydroxy or mercapto are obtained by replacing the 7-chlorine atom of the corresponding 7-chloro compound (a) by dissolving in dimethylformamide, adding sodium acetate and heating, followed by treatment with NaOH solution; or (b) by heating with a mixture of Na 2 S.H 2 O and S in ethanol which has been refluxed for 30 minutes. 3 - Amino - 5 - X - 6 - iodopyrazinonitriles are obtained by catalytic hydrogenolysis of a 3- amino-5-X-6-(chloro or bromo) - pyrazinonitrile using Pd-on-charcoal catalyst in the presence of MgO to form a 3-amino-5-X-pyrazinonitrile which is then iodinated using iodine and mercuric acetate in a solvent such as aqueous dioxane or tetrahydrofuran preferably with heating at 50-100‹ C. for 5-30 minutes. 3 - Amino - 6 - iodopyrazinonitrile is obtained by reacting methyl 3-amino-6-iodopyrazinoate with ammonium hydroxide to form 3-amino-6- iodopyrazinamide which is treated with dimethyl formamide and phosphoral chloride to give N,N - dimethyl - N<SP>1</SP> - (3 - cyano - 5 - iodo- 2-pyrazinyl) formamidine which is hydrolysed to yield the desired product. 3 - Amino - 5 - X - 6 (chloro or bromo) - pyrazinonitriles are described in Specification 1,149,639. Pharmaceutical compositions having diuretic and saluretic properties comprise a compound of Formula I above together with an inert diluent, carrier or coating in forms suitable for oral or parenteral administration.