Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Patent
1995-01-25
1997-06-03
Ford, John M.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
540226, 540227, 514206, C07D50148, A61K 31545
Patent
active
056355017
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 of PCT/GB93/01310, filed 21 Jun. 1993.
This invention relates to novel .beta.-lactam compounds, their preparation and their use, and in particular to a novel class of cephalosporins. These compounds have antibacterial properties, and are therefore of use in the treatment of bacterial infections in humans and animals caused by a wide range of organisms.
WO 92/01696 (Beecham Group plc) discloses cephems of general formula (A): ##STR2## wherein R.sup.a, R.sup.b and R.sup.c are various substituents and m is 0 or 1. EP 0477717A (Bayer) discloses an analagous class of compounds having a furyl ring in place of the tetrahydrofuranyl ring shown in formula (A).
We have found a particularly advantageous class of cephems and carbacephems bearing a cyclic ether or thio-ether substituent at the 3-position of the cephem nucleus.
The present invention provides a compound of formula (I) or a salt thereof: ##STR3## wherein: R.sup.1 is hydrogen, methoxy or formamido; cephalosporin; readily removable carboxy protecting group or a pharmaceutically acceptable salt-forming group or in vivo hydrolysable ester group; present on any of the carbon atoms in the ring system shown, selected from alkyl, alkenyl, alkynyl, alkoxy, hydroxy, halogen, amino, alkylamino, acylamino, dialkylamino, CO.sub.2 R, OCOR, CONR.sub.2, SO.sub.2 NR.sub.2 where R is hydrogen or alkyl, aryl and heterocyclyl, which may be the same or different and wherein any R.sup.4 alkyl substituent is optionally substituted by one or more substituents selected from the list from which R.sup.4 is selected; m is 1 or 2; and wherein in the ##STR4## ring system the dotted line indicates that one pair of adjacent ring carbon atoms is joined by a C.dbd.C double bond.
The bonding carbon atom of the unsaturated cyclic ether or thio-ether moiety which links the ring to the cephalosporin nucleus is generally asymmetric. The present invention includes either stereoisomer, as well as mixtures of both isomers.
In compounds of formula (I) wherein R.sup.1 is formamido, the formamido group can exist in conformations wherein the hydrogen atoms of the --NH--CHO moiety are cis- or trans-; of these the cis conformation normally predominates.
Since the compounds of the present invention are intended for use as therapeutic agents for antibacterial use in pharmaceutical compositions, it will be readily appreciated that preferred compounds within formula (I) are pharmaceutically acceptable, i.e. are compounds of formula (Ia) or pharmaceutically acceptable salts or pharmaceutically acceptable in vivo hydrolysable esters thereof: ##STR5## wherein R.sup.1, R.sup.2, R.sup.4, m, n, Y, and y are as defined with respect to formula (I) and the group CO.sub.2 R.sup.6 is CO.sub.2 R.sup.3 where CO.sub.2 R.sup.3 is a carboxy group or a carboxylate anion.
Accordingly, the present invention provides a compound of formula (Ia) or a pharmaceutically acceptable salt or in vivo hydrolysable ester thereof, for use as a therapeutic agent, and in particular an in vivo hydrolysable ester thereof for use as an orally administrable therapeutic agent.
The present invention further provides a compound of formula (Ia) or a pharmaceutically acceptable salt or in vivo hydrolysable ester thereof, for use in the treatment of bacterial infections, more particularly an in vivo hydrolysable ester thereof for use in the oral treatment of bacterial infections.
The present invention also includes a method of treating bacterial infections in humans and animals which comprises the administration of a therapeutically effective amount of an antibiotic compound of the formula (Ia) or a pharmaceutically acceptable in vive hydrolysable ester thereof, in particular the oral administration of a therapeutically effective amount of an in vivo hydrolysable ester.
In addition, the present invention includes the use of a compound of formula (Ia) or a pharmaceutically acceptable salt or in vivo hydrolysable ester thereof, for the manufacture of a medicament for the treatment of bacterial infections, in particular the us
REFERENCES:
patent: 5246926 (1993-09-01), Bateson et al.
J. of Antibiotics, vol. 45, No. 12, pp. 1929-1938 Dec. 1992, Koyama et al.
Bateson John H.
Burton George
Elliott Richard L.
Fell Stephen C. M.
Creagan B. Timothy
Ford John M.
Holtrust Gezina
Pfizer Inc.
Richardson Peter C.
LandOfFree
Alphalosporins and 1-carba-1-dethia cephalosporins does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Alphalosporins and 1-carba-1-dethia cephalosporins, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Alphalosporins and 1-carba-1-dethia cephalosporins will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-391832