Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Patent
1992-06-12
1994-09-20
Rizzo, Nicholas S.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
514204, 540222, 540226, 540223, C07D50120, A61K 31545
Patent
active
053489527
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to new cephalosporins, their preparation and to pharmaceutical and veterinary compositions containing them.
The compounds disclosed in the present invention feature the simultaneous presence on the cephem skeleton of an acyl group at C-4 and a sulphenyl, sulphinyl or sulphonyl group at C-2.
According to the invention there are provided cephalosporins of formula (I) and the pharmaceutically and veterinarily acceptable salts thereof: ##STR2## wherein m is one or two; n is zero, one or two; C.sub.1 -C.sub.12 straight or branched alkyl; C.sub.2 -C.sub.10 alkenyl; C.sub.2 -C.sub.10 alkynyl; C.sub.6 -C.sub.10 aryl; C.sub.3 -C.sub.8 cycloalkyl; C.sub.5 -C.sub.8 cycloalkenyl; aralkyl, aralkenyl, aralkynyl or (cycloalkyl)alkyl wherein the aryl, cycloalkyl, alkyl, alkenyl and alkynyl groups are as defined above; a first 5- or 6-membered, saturated or unsaturated, heterocyclyl ring, containing at least one heteroatom chosen from O, S and N, which is optionally fused to a second said 5- or 6-membered heterocyclyl group or to a C.sub.3 -C.sub.8 cycloalkyl group; or heterocyclylalkyl, heterocyclylalkenyl or heterocyclylalkynyl wherein the heterocyclyl, alkyl, alkenyl and alkynyl groups are as defined above; wherein each of the said organic radicals is unsubstituted or substituted by one or more atom or group selected from; different, are C.sub.1 -C.sub.7 straight or branched alkyl, phenyl or benzyl; ; N-(carboxymethyl)carbamoyl --CONH--CH.sub.2 CO.sub.2 H; above; above; defined above; is as defined above; straight or branched alkyl, phenyl, benzyl, CH.sub.2 CH.sub.2 CO.sub.2 H or CH.sub.2 CH.sub.2 CH.sub.2 CO.sub.2 H; fluoromethyl, difluoromethyl, trifluoromethyl, aminomethyl, azidomethyl, cyanomethyl, carboxymethyl, carbamoylmethyl, carbamoyloxymethyl, hydroxymethyl, C.sub.3 -C.sub.4 alkoxycarbonylmethyl, guanidinomethyl; 0, 1 or 2 and wherein A is as defined above; wherein Z is a mono, di- or tripeptide composed of D or L .alpha.-aminoacids chosen from Ala, Gly, Val, Leu, Ile, Phe and Pro, and with the terminal amino group either free, or acylated by a group --C(O)R'" or --C(O)OR'" wherein R'" is as defined above; A are as defined above; above; S(O).sub.n A wherein n and A are as defined above; A and Z are as defined above; above; and A', being the same or different, is as defined for A; or A and A' taken together with the nitrogen atom to which they are attached represent a heterocyclic ring; ##STR3## wherein A and A' are as defined above and A", being the same or different, is as defined for A; or A is alkyl and A' and A" together with the nitrogen atom to which they are attached represent a heterocyclic ring; or A, A' and A" together with the nitrogen atom to which they are attached represent an aromatic heterocyclic ring; or and Z are as defined above.
The present invention provides the salts of those compounds of formula (I) that have salt-forming groups, especially the salts of the compounds having a carboxylic group, a basic group (e.g. an amino or guanidino group), or a quaternary ammonium group. The salts are especially physiologically tolerable salts, for example alkali metal and alkaline earth metal salts (e.g. sodium, potassium, lithium, calcium and magnesium salts), ammonium salts and salts with an appropriate organic amine or amino acid (e.g. arginine, procaine salts), and the addition salts formed with suitable organic or inorganic acids, for example hydrochloric acid, sulphuric acid, carboxylic and sulphonic organic acids (e.g. acetic, trifluoroacetic, p-toluensulphonic acid). Some compounds of formula (I) which contain a carboxylate and an ammonium group may exist as zwitterions; such salts are also part of the present invention.
The present invention encompasses all the possible stereoisomers and tautomers, as well as their racemic or optically active mixtures. However, the configurations depicted in formula (I') are particularly preferred ##STR4## wherein m is one or two; n is zero, one or two; alkynyl; C.sub.3 -C.sub.8 cycloalkyl; dimethylphenyl, diphenylmethyl; phenyl
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Alpegiani Marco
Bissolino Pierluigi
Cassinelli Giuseppe
Franceschi Giovanni
Orezzi Piergiuseppe
Farmitalia Carlo Erba S.r.l.
Rizzo Nicholas S.
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