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AssigneeGlaxo Laboratories Limited
InventorsMartin Christopher Cook, Gordon Ian Gregory, Janice Bradshaw
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The invention provides novel antibiotic compounds which are 7.beta.-acylamidoceph-3-em-4-carboxylic acids, and non-toxic derivatives thereof characterized in that the acylamido group has the structure ##STR1## where R is a hydrogen atom or an organic group and R.sup.a is an etherifying monovalent organic group linked to the oxygen atom through a carbon atom. The compounds are syn isomers or exist as mixtures containing at least 75% of the syn isomer. These antibiotic compounds possess high antibacterial activity against a range of gram positive and gram negative organisms coupled with particularly high stability to .beta.-lactamases produced by various gram negative organisms. The invention is also concerned with the administration of the compounds.
A compound selected from the group consisting of a cephalosporin antibiotic of the formula:
Dependencies are inferred from the claim text.
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With only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms: with substituted hydrocarbon…
With the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms: to carbon atoms of hydrocarbon radicals…
Iso-indoles; Hydrogenated iso-indoles: with oxygen atoms in positions 1 and 3, e.g. phthalimide
Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals:…
Term ended 20 Dec 1994 (estimated)
USPTO file history isn’t available for this patent, so only indexed dates are shown.
This invention is concerned with improvements in or relating to antibiotics of the cephalosporin series.
The cephalosporin compounds referred to in this specification are generally named with reference to cepham (J. Amer. Chem. Soc. 1962, 84 3400). The term "cephem" refers to the basic cepham structure with one double bond.
As is well known, antibiotics of the cephalosporin series are 7.beta.-acylamido-ceph-3-em-4-carboxylic acids and their various non-toxic derivatives e.g. salts, esters, lactones (if such can be formed), amides, hydrates or the corresponding sulphoxides. These antibiotics may contain various substituents particularly at the 3-position including unsubstituted methyl and methyl groups substituted with a variety of substituents as is described in the literature.
The following examples illustrate the invention.
A solution of sodium (5 g.) in dry methanol (100 ml) was added to a solution of O-methylhydroxylamine hydrochloride (15 g.) in dry methanol (100 ml) until neutral to phenolphthalein. The precipitated sodium chloride was removed by filtration, and the filtrate added to a solution of phenylglyoxylic acid (25 g.) in dry methanol (100 ml). The solution was refluxed for 2 hours, cooled, and evaporated to an oil, which was dissolved in ether (200 ml), refiltered and evaporated to an oil (32.9 g.). This was crystallised from petroleum spirit, (bp. 60.degree.-80.degree.) producing a white solid (19.61 g.) and oil (3.9 g.).
The solid (17.8 g.) and the oil (3.9 g.) were combined (21.7 g.) and methylated with ethereal diazomethane, producing an oil (24.2 g.). This was purified by chromatography on silica gel (600 g.), producing syn-methyl 2-methoxyiminophenylacetate as an oil (13.6 g. 55%), .lambda..sub.max. (EtOH) 259 nm (.epsilon. 10,400) and anti-methyl 2-methoxyiminophenylacetate, the slower component, as a solid (8.7 g.; 35%), m.p. 54.degree., .lambda..sub.max. (EtOH) 251 nm (.epsilon. 7,260).