Patent GB-892593-A (GB)
Title: New hydroxamic acid esters
IPC: A61K39/39
Filed: 1959-04-30
Abstract: The invention comprises aminoalkanol esters of aliphatic hydroxamic acids and their salts and quaternary ammonium derivatives, in which the alcohol radical is that of a lower alkanol having 2-6 carbon atoms and the amino or ammoniun group is separated from the ester oxygen atom by at least 2 carbon atoms.  Preferred N-acyl radicals in the hydroxamic acids are those having from 10 to 22 carbon atoms which are saturated or unsaturated.  The amino group is advantageously substituted or disubstituted with alkyl, alkenyl, aza-, oxa, or thia-alkyl, or alkylene, cycloalkyl, aralkyl, such as benzyl, aryloxyalkyl, such as phenyl-oxyalkyl or heterocyclyalkyl. Representative of the radicals specified are from methyl to pentyl, butylene (1 : 4), pentylene-(1 : 5), 3-oxa, or 3-aza-pentylene-(1 : 5), benzyl, phenoxyethyl and tetrahydro-furfuryl.  The products are employed in disinfectant and pharmaceutical compositions (see Group VI). The products may be obtained by methods known in themselves, e.g. by reacting an aliphatic carboxylic acid or functional derivative thereof such as an ester, halide, amide or anhydride with an O-(aminoalkyl)-hydroxylamine.  The reactions may be carried out in the presence or absence of diluents, in the presence of condensation agents, e.g. pyridine, at normal or elevated temperature.  Acids specified for use in the preparation of salts include the usual mineral acids, perchloric acid, methane-, hydroxyethane-, benzene-p-toluene- and naphthalene sulphonic acids, acetic, propionic, oxalic, tartaric, citric, lactic, maleic, benzoic, salicylic, p-aminosalicylic acids, amino acids and alkyl sulphuric acids.  Quaternating agents specified include esters of alcohols, especially alkanols, aralkanols and aryloxyalkanols, with strong inorganic or organic acids, such as hydrogen halides, sulphuric acid or organic sulphonic acids, e.g. benzene- and toluene sulphonic acids.  The examples relate to the preparation of b -diethyl- and dimethylaminoethyl and b -piperidino-ethyl esters of stearyl hydroxamic acid, the b -diethylaminoethyl ester of lauroyl hydroxamic acid and the quaternary products obtained with methyl iodide.  The conversion of stearyl hydroxamine (b -N,N-diethyl-N-methyl ammonium ethyl) ester iodide to the chloride by treatment with silver chloride is also described.ALSO:Disinfectant and pharmaceutical compositions comprise aminoalkanol esters of aliphatic hydroxamic acids, their salts and quaternary ammonium derivatives in which the alcohol radical is that of a lower alkanol having 2-6 carbon atoms and in which the amino or ammonium group is separated from the ester oxygen atom by at least 2 carbon atoms (see Group IV (b)).  Esters specified include stearylhydroxamic acid (b -dimethylamino- and b piperidino-ethyl) esters, lauroyl-hydroxamic acid (b -diethylamino-ethyl) ester and their salts and N-methyl quaternary salts such as chlorides and iodides and in particular stearylhydroxamic acid-(b -diethyl-methyl-ammonium-ethyl) halides, e.g. the chloride.  Conventional carriers may be employed in the disinfectant composition and in the pharmaceutical compositions organic or inorganic carriers suitable for enteral, parenteral and topical application may be used, e.g. gelatine, water, lactose, petroleum jelly, starches, magnesium stearate, talc, vegetable oils, benzyl alcohol, gums, polyalkylene glycols and cholesterol.  The pharmaceutical preparations may be made up in the form of tablets, dragees, salves or as solutions, suspensions or emulsions.  Wetting and emulsifying agents may be present.  The active substances of the invention may be employed as adjuvants in vaccines.