Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Patent
1996-05-09
1997-12-02
Shah, Mukund J.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
540302, A61K 31395
Patent
active
056936346
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 of PCT/GP94/03686 dated Nov. 9, 1994.
This invention relates to urea derivatives having antibacterial activity, to processes for their preparation, to compositions containing them and to their use in medicine.
European Patent Application publication No. 0416953A2 describes !undec-2-ene-2-carboxylic acid and certain 4 substituted derivatives thereof, which have antibacterial activity.
European Patent Application publication No. 0422596A2 describes compound of the general formula ##STR2## wherein R.sup.1 is inter alia a 1-hydroxyethyl group, CO.sub.2 R.sup.2 is a carboxy group which may optionally be esterified and ring B is a cyclic group which may be optionally substituted. Ring B may inter alia be a cyclohexane ring. The compounds have antibacterial activity. The specification specifically teaches compounds wherein B is an unsubsituted cyclohexane ring. but there is no teaching of specfic compounds wherein the cyclohexane ring is substituted.
European Patent Application No. 0507313A1 describes inter alia compounds of formula ##STR3## wherein R.sup.1 is inter alia an optionally substituted lower alkyl group, CO.sub.2 R.sup.2 is a carboxy group which may be esterified, ring A is inter alia a cyclohexane ring and R.sup.a is the group W.sup.a U.sup.a dioxide), oxygen, NH (which may be substituted) or a straight-chain or branched lower alkylene or alkenylene group which may be interrupted by sulphur (which may be in the form of mono- or dioxide), oxygen or NH (which may be substituted); U.sup.a is carbamoyl, acyl which may be substituted, alkylammonium which may be substituted or a group of the formula ##STR4## is a quaternized nitrogen-containing heterocyclic group which may be substituted and R.sup.d is an alkyl group which may be substituted)! which compounds have antibacterial activity. Preferred compounds of this class !undec-2-ene-2-carboxylic acid, derivatives wherein the group R.sup.a is (CH.sub.2)mK.sup.a (CH.sub.2)nU.sup.a (wherein K.sup.a is CH.sub.2, O, S or NH; m and n each is a whole number of 0 to 3; and U.sup.a is an N-linked quaternary ammonium group.
We have now discovered that the introduction of certain urea groupings at !undec-2-ene-2-carboxylic acid provides compounds with a particularly useful profile of activity as antibacterial agents.
According to the present invention, therefore we provide compounds of general formula (I) ##STR5## salts and metabolically labile esters thereof; wherein R represents hydrogen or C.sub.1-6 alkyl; alkynyl, aryl, cycloalkyl or heterocyclic group.
In addition to the fixed stereochemical arrangement as defined in formula (I) the molecule contains a further asymmetric carbon atom at the 8-position, and another at the 4-position. It will be appreciated that all stereoisomers including mixtures thereof arising from these additional asymmetric centres, are within the scope of the compounds of formula (I). Compounds of formula (I) may also exist in tautomeric forms and such tautomers and derivatives thereof are also within the scope of the invention
Salts of compounds of formula (I) include base addition salts for use in medicine such salts are formed with bases that have a physiologically acceptable cation. Suitable cations include those of alkali metals (e.g. sodium or potassium), alkaline earth metals (e.g. calcium), amino acids (e.g. lysine and arginine) and organic bases (e.g. procaine, phenylbenzylamine, dibenzylethylenediamine, ethanolamine, diethanolamine, and N-methyl glucosamine).
Salts derived from bases wherein the cation is not physiologically acceptable may be useful as intermediates for the preparation and/or isolation of other compounds of the invention, and these salts also form part of the invention.
When the group R.sub.2 contains a basic centre, acid addition salts of such compounds and internal salts formed with the carboxylic acid grouping are also included in the invention.
It will be appreciated that the compounds of formula (I) may be produced in vivo by metabolism of a suitable metabolically labile ester. Exampl
REFERENCES:
patent: 5459260 (1995-10-01), Sendai et al.
Andreotti Daniele
Pentassuglia Giorgio
Perboni Alcide
Winders John Alexander
Bucknum Michael
Glaxo Wellcome S.p.A.
Shah Mukund J.
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