Patent GB-948076-A (GB)
Title: Cephalosporin compounds
IPC: C07D501/24
Filed: 1960-10-25
Abstract: The invention relates to cephalosporins having the formulae: <FORM:0948076/C2/1> and the physiologically acceptable cationic salts of the acid form thereof wherein R is an a  or b -halo substituted alkyl containing from 1 to 6 carbon atoms; a -phenyl-b -hydroxylalkyl containing from 1 to 5 carbon atoms or a -substituted phenyl-b -hydroxy ethyl wherein the substituent is alkyl containing 1 to 4 carbon atoms, halogen, trifluoromethyl, alkoxy containing 1 to 4 carbon atoms, nitro, amino or hydroxyl; amino or substituted amino wherein the substituent is alkyl containing 1 to 10 carbon atoms, phenyl, p-dimethylaminophenyl, nitrophenyl, p-carbomethoxyphenyl, p-chlorophenyl, p-ethoxyphenyl, p-methoxyphenyl or naphthyl;aminoalkyl wherein the alkyl group is phenyl substituted ethylene or a straight chain or branched chain alkylene radical containing 1 to 8 carbon atoms or a N-carbobenzoxy derivative thereof; a -allyl mercapto alkyl wherein the alkyl is alkyl containing 1 to 6 carbon atoms; cis or trans-styryl mercapto methyl, n-pentyl, 2-pentenyl, n-heptyl, phenyl mercapto methyl, p-hydroxybenzyl, a -phenylmercapto -b - hydroxyalkyl or a - phenoxy -b -hydroxyalkyl wherein the alkyl group contains 1 to 7 carbons atom, or the b -acyl derivatives thereof wherein the acyl group is an acyl radical of a hydrocarbon monocarboxylic acid containing 1 to 4 carbon atoms; and compounds wherein R.CO is replaced by:- <FORM:0948076/C2/2> wherein X is oxygen or sulphur; R1 is alkyl containing 1 to 7 carbon atoms, substituted alkyl wherein the substituent is nitro, alkoxy having 1 to 5 carbon atoms, alkyl mercapto having 1 to 5 carbon atoms, phenyl, phenoxy, phenylmercapto, chloro or bromo; cyclohexyl, cyclopentyl, benzyl, a -methyl benzyl, allyl, phenyl or substituted phenyl wherein the substituent is chloro, bromo, alkyl having 1 to 5 carbon atoms, alkoxy having 1 to 5 carbon atoms or nitro; substituted benzyl wherein the substituent is chloro, bromo, alkyl or alkoxy each containing 1 to 5 carbon atoms or nitro; and <FORM:0948076/C2/3> wherein M is hydroxy, alkoxy containing 1 to 4 carbon atoms, amido, carboxymethyl imido, or carboxy ethylidene imido; R2 is methylene or ethylidene; R3 is cycloalkylene of 4 to 6 carbon atoms, phenylene, 2,5-thienylene, 2-carboxy-3,4-thienylene, methylene or substituted methylene wherein the substituent is carboxy or halogen; alkylene containing 2 to 4 carbon atoms which may be unsaturated or substituent derivatives thereof wherein the substituent is hydroxy carboxy, halogen or an alkanoyloxy radical of a hydrocarbon carboxylic acid containing 1 to 4 carbon atoms; and R1 is 1-pyridyl or alkanoyloxy containing 2 to 6 carbon atoms.  The compounds specified above are prepared by reacting the corresponding free amino compound with an appropriate acid halide, acid anhydride cyanate or isocyanate.  The compounds in which R.CO is replaced by the phosphorus grouping (R1O)2 PX wherein R1 and X are as defined above are prepared by reacting the corresponding free amino compound with an appropriate O, O-disubstituted halophosphate or thiono phosphate. The starting compounds 7-amino cephalosporanic acid and its desacetyl lactone are produced from Cephalosporin C by treatment of Cephalosporin C with an aqueous solution of dilute mineral acid or a strong cation exchange resin (H+ cycle). Specified salts are the sodium potassium, calcium, ammonium, amine, procaine, N,N1-dibenzyl ethylenediamine, dibenzylamine, 1-ephenamine, N-benzyl -b - phenyethylamine and benzhydrylamine salts.  The compounds may be used in pharmaceutical compositions for oral or parenteral administration as tablets, capsules, elixirs or suspensions.