Patent GB-810569-A (GB)
Title: Penicillin salts of aminoguanidines
Inventor: TAYLOR ALAN
IPC: C07D499/00
Filed: 1956-05-18
Abstract: The invention relates to salts of penicillins with aminoguanidines of formula <FORM:0810569/IV (b)/1> wherein A stands for an aryl radical which may optionally bear one or more halogen, alkyl or alkoxy substituents and wherein the amino group may optionally be substituted by alkyl groups, by alkylidene groups for example cycloalkylidene groups or by aralkylidene groups optionally substituted by dialkylamino radicals for example benzylidene and p-dimethylamino benzylidene groups.  The free base may be reacted with the free penicillin in the presence of an inert liquid medium especially an organic liquid such as chloroform or butyl acetate.  A water-soluble salt of penicillin such as an alkali metal salt and a water-soluble salt of the aminoguanidine such as the hydrochloride or hydriodide may be reacted in an aqueous medium.  Alternatively, the salts may be reacted in the presence of a mutual organic solvent therefor. The salts may be used in the isolation and purification of penicillin from the solvent extracts or buffered alkaline extracts of fermented culture media and may then be converted into other salts such as the sodium, potassium or procaine salts.  Preferred penicillins are penicillin-G, penicillin-V (phenoxymethyl penicillin) and p-chlorophenylthiomethylpenicillin and preferred salts are salts of these penicillins with N - amino - N1 - 2,5 - dimethylphenylguanidine.  Other salts are salts of pencillins G and/or V with N-amino-N1-phenylguanidine, N - amino - N1 - p - phenetylguanidine, N - amino - N1 - m - chlorophenylguanidine, N - amino - N1 - (2,4 - dimethylphenyl) guanidine, N - amino - N1 - (3,4 dimethylphenyl) guanidine, N - amino - N1 - (2,4 - dichlorophenyl chlorophenyl) guanidine, N-amino - N1 - (2,5 dimethyl phenyl) guanidine, N - amino - N1 - (2,6 dimethylphenyl) guanidine, N - amino - N1 - (2,4,5 - trimethylphenyl) guanidine, N - p - chlorophenyl - N1 - n - nonylaminoguanidine, N - cyclohexylidene amino-N1 - (2,4 dimethylphenyl) guanidine and (p-dimethylaminobenzylidene) amino - N1 - phenylguanidine.  The penicillin salts are used in pharmaceutical compositions (see Group VI).ALSO:Pharmaceutical compositions comprise one or more salts of penicillin with aminoguanidines of formula <FORM:0810569/VI/1> wherein A stands for an aryl radical which may optionally bear one or more halogen, alkyl or alkoxy substituents and wherein the amino group may be substituted by alkyl, alkylidene, e.g. cycloalkylidene or aralkylidene optionally substituted by dialkylamino, e.g. benzylidene and p-dimethylaminobenzylidene (see Group IV (b)) in admixture with a diluent or carrier.  The penicillin is especially penicillin G, penicillin V or p-chlorophenylthiomethylpenicillin.  The composition may be in the form of tablets, aqueous suspensions, dispersible powders or solutions or suspensions in non-aqueous liquids, e.g. dimethylacetamide.  Diluents specified are suspending agents such as sodium carboxymethylcellulose, sweetening agents such as sucrose, wetting agents such as sodium di-isobutylnaphthalene sulphonate, calcium carbonate, maize starch and magnesium stearate.