Abstract: Inhibitors of the enzyme beta-lactamase are provided. The compounds are adapted to inhibit beta-lactamase as produced by beta-lactam resistant bacterial strains. Methods of treatment of beta-lactam resistant bacterial infections in patients are provided.

Abstract: Provided herein are imaging methods for detecting, diagnosing and imaging pathogenic bacteria or a pathophysiological condition associated therewith using fluorogenic substrates for bacterial enzymes. Fluorescent, luminescent or colorimetric signals emitted by substrates or enzyme products in the presence of the bacteria are compared to controls to detect and locate the pathogenic bacteria. Provided is a method for screening therapeutic agents to treat the pathophysiological conditions by measuring a signal emitted from the fluorogenic substrates or products in the presence and absence of the potential therapeutic agent. In addition, a diagnostic method for detecting a mycobacterial infection in a subject by contacting biological samples with a fluorogenic substrate and imaging for signals emitted from a mycobacterial beta-lactamase product.

Abstract: Compounds of general formula (II), wherein R1 represents R4 represents hydrogen or —CHO group, R5 represents hydrogen or trityl, R2 represents hydrogen or methoxy group, R3 represents —CH?CH2 or and M represents a dialkyl or dicycloalkyl ethylenediamine group selected from N,N?-diisobutylethylenediamine, N,N?-dicyclohexylethylenediamine, and N,N?-dicyclopentylethylenediamine, are useful in a process to make cephalosporin antibiotics of formula (I) wherein R represents hydrogen or pharmaceutically acceptable esters or alkali metals salts.

Abstract: Method for purifying 7?-methoxy-cephalosporins containing as impurity the corresponding 7?-methylthio analogue, which is transformed into its methoxy analogue by treatment with a halogenating agent in methanol. In this way the complete conversion of the sulphurated impurity into the corresponding methoxy analogue is obtained.

Abstract: There is provided an improved process for preparing cefixime. Thus, for example, 7-amino-3-vinyl-3-cephem-4-carboxylic acid is reacted with 2-mercapto-1,3-benzothiazolyl-(Z)-2-(2-aminothiazol-4-yl)-2-(methoxycarbonyl)-methoxyimino acetate in tetrahydrofuran and water at 4° C. in the presence of triethylamine. The reaction mass is extracted with ethyl acetate. 7-[2-(2-Amino-4-thiazolyl)-2-(methoxycarbonylmethoxyimino)acetamido]-3-vinyl-3-cephem-4-carboxylic acid triethylamine salt present in the aqueous layer is hydrolyzed with sodium hydroxide in less than 30 minutes and aqueous hydrochloric acid is added immediately to adjust the pH to 4.8 to 5.2. Then, aqueous hydrochloric acid is added at 35° C. to adjust the pH 2.5 and cooled to crystallize cefixime trihydrate in high purity.

Abstract: A process for the preparation of cefoxitin of formula (I) The process includes treating the compound of formula (II) with a halogenating agent in an organic solvent, followed by treatment with alkali/alkaline earth metal methoxide at a temperature in the range of ?100° C. to 0° C. The product formed is then isolated as an organic amine salt of the formula (III), The salt of formula (III) is treated with a base in the presence of solvent at a temperature in the range of ?75 to 10° C., the product formed is isolated as an organic amine salt of the formula (IV) The compound of formula (IV) is carbamoylated with isocyanate of formula (V) RNCO??(V) in the presence of a solvent at a temperature in the range of ?60° C. to 10° C., and isolating to get cefoxitin of the formula (I).

Abstract: Cefalotin is methoxylated in position 7?, desacetylated and then carbamoylated in position 3, to provide acid cefoxitin without any isolation of intermediate products. The acid cefoxitin is then transformed into the sodium salt by means of ion exchange resin.

Abstract: The invention relates to a method for obtaining cefotetan acid substantially free of tautomer, by treating crude cefotetan with Al3+ ions which cause the tautomer to precipitate. The precipitate is eliminated by filtration to provide a solution from which practically tautomer-free cefotetan is obtained.

Abstract: Process for producing 7-methoxy-3-desacetylcefalotin by a hydrolysis process which takes place in water and is catalyzed by an enzyme. Cefoxitin can be obtained from this compound by known methods.

Abstract: The present invention relates to an improved process for the preparation of cephalosporin antibiotics of formula (I). The present invention also provides new salts of compound of formula (II) and a process for the preparation of these new salts, where n=0.5 to 2. The present invention also provides a process for the preparation of compound of formula (I) using the new salts of formula (II).

Abstract: Derivatives of 7-alkylidene cephalosporanic acid sulfone and the pharmaceutically active salts thereof are found to be potent inhibitors of &bgr;-lactamase enzymes.

Abstract: Matrix metalloproteinases (MMPs) are a group of enzymes that have been implicated in the pathological destruction of connective tissue and basement membranes. These zinc containing endopeptidases consist of several subsets of enzymes including collagenases, stromelysins and gelatinases. TNF-&agr; converting enzyme (TACE), a pro-inflammatory cytokine, catalyzes the formation of TNF-&agr; from membrane bound TNF-&agr; precursor protein. It is expected that small molecule inhibitors of MMPs and TACE therefore have the potential for treating a variety of disease states.

Abstract: The present invention relates to cephem-derivatives and to a process for their preparation, having proper substituents at C-2 position, i.e. heterocyclylthio or acyloxy group. They are potent protease inhibitors, in particular human leucocyte elastase (HLE) inhibitors.

Abstract: This invention relates to new benzoxazinedione derivatives corresponding to the formula I: ##STR1## wherein R.sup.1 =H or carboxyalkyl, R.sup.2 =H, alkyl or phenyl, and R.sup.3 represents different acid groups derived from amino acids, dipeptides and hydrazones or conjugates thereof with active ingredients, e.g. antibiotics. The compounds may be present as free acids, in the form of their salts or as readily cleavable esters. The compounds according to the invention constitute heterocyclically protected catechol derivatives and are effective as siderophores against gram-negative bacterial strains, particularly against Pseudomonads and strains of E. coli and Salmonella. In the form of their conjugates with active ingredients, e.g. antibiotics (as "siderophore-antibiotic conjugates"), they can transport the latter into bacterial cells and can improve or extend the antibacterial effect thereof, sometimes even in relation to bacterial strains which are resistant to other .beta.-lactams.

Abstract: .beta.-Lactam antibiotics of formula (I) or a salt thereof, wherein R.sup.1 is hydrogen, methoxy or formamido; R.sup.2 is an acyl group; CO.sub.2 R.sup.3 is a carboxy group or a carboxylate anion, or R.sup.3 is a readily removable carboxy protecting group; R.sup.4 represents up to four substituents; X is S, SO, SO.sub.2, O or CH.sub.2 ; m is 1 or 2; and n is 0, useful in the treatment of bacterial infections.

Abstract: The invention provides a process for preparing an allenyl .beta.-lactam of formula (4), by reacting the hydroxyl group of a .beta.-lactam of formula (1) with a reactive derivative of sulfonic acid of formula (2) to convert the compound of formula (1) to a .beta.-lactam of formula (3), thereafter reacting the resulting .beta.-lactam with a basic anion exchange resin of the type having a tertiary organic base fixed to the resin and isolating the allenyl .beta.-lactam of formula (4) with stability and high purity in a high yield.The invention also provides a process for preparing an allenyl .beta.-lactam of formula (4), by reacting the hydroxyl group of a .beta.-lactam compound of formula (1) with a reactive derivative of sulfonic acid of formula (2) to convert the compound of the formula (1) to a .beta.-lactam compound of formula (3), thereafter reacting the resulting .beta.-lactam of formula (3) with a tertiary organic base to convert the compound (3) to the allenyl .beta.

Abstract: Cephalosporin derivatives of formula ##STR1## wherein R.sub.1 signifies hydrogen or a silyl protecting group, processes for their production and their use as intermediate products.

Abstract: A new process is described for the production of 6-alpha-amino-penicillins and 7-alpha-amino-desacetoxy-cephalosporins free from halogen-containing solvents by acylating 6-APA, 7-ADCA or a derivative thereof in a halogen-free solvent.

Abstract: The present invention relates to compounds of formula I ##STR1## wherein R.sup.1 is a group selected from 2-, 3-, and 4-hydroxyphenyl, 3-nitrophenyl, and 3-fluoro-4-hydroxyphenyl; as well as readily hydroyzable esters thereof, pharmaceutically acceptable salts of said compounds and hydrates of the compounds of formula I and of their esters and salts.

Abstract: The present invention provides a process for the substitution of an acylamino .beta.-lactam compound at the carbon atom carrying the acylamino group, which process comprises reacting the .beta.-lactam compound with an halogenating agent and a nucleophilic reagent; characterized in that the acylamino group has an acidic group on the carbon atom adjacent the carbonyl group.In particular the process of this invention comprises reacting a .beta.-lactam of partial structure (I): ##STR1## where X represents an acidic group; with an halogenating agent and a nucleophilic reagent.

Abstract: A new process is described for the production of 6-alpha-amino-penicillins and 7-alpha-amino-desacetoxy-cephalosporins free from halogen-containing solvents by acylating 6-APA, 7-ADCA or a derivative thereof in a halogen-free solvent.

Abstract: A group of reagents, as diisocyanates, dianhydrides, diacidchlorides, diepoxides, carbodiimides and the like are utilized to link a wide variety of antibiotic moities, reacted two at a time with said reagents, the said antibiotic moieties containing groups reactive with the linking reagents as carboxylic acid, alcolhol, primary amine, and secondary amine functional groups, said functional groups being present as singularities or as multiplicities, products being readily purified using chromatographic techniques, and said products of above reactions being valuable for the treatment of microbial infections of man and animals.

Abstract: The invention relates to a new economical and simple process, using a new intermediate compound, for the production of 3'-substituted 7-amino-3-propenyl-4-cephem-carboxylic acid derivatives of formula ##STR1## wherein R is hydrogen, a negative charge or a silyl protecting group, R.sub.o is hydrogen or methoxy, R.sub.1 is hydrogen or a silyl protecting group and X is the radical of a nucleophile, and their acid addition salts.

Abstract: A compound selected from the group consisting of a compound of the formula ##STR1## wherein R is selected from the group consisting of ##STR2## and R.sub.b --NH--, Ra is an organic radical, Ri and Rj are individually selected from the group consisting of hydrogen, aliphatic hydrocarbon, aromatic hydrocarbon and heterocycle or taken together with the nitrogen atom to which they are attached form an optionally substituted ring, Rb is selected from the group consisting of carbocyclic aryl and heterocyclic aryl, both optionally substituted, R.sub.1A is selected from the group consisting of ##STR3## and ##STR4## are individually selected from the group consisting of hydrogen and alkyl of 1 to 4 carbon atoms, Z.sub.A is selected from the group consisting of a simple bond, --O-- and optionally oxidized sulfur, R.sub.

Abstract: A substantially flat collapsed plastic bag with an evacuation form unit insert positioned therein as manufactured to serve as a form about which the filled bag will collapse as it is emptied. The form unit comprises a ring for mounting the unit on the spout of the bag and a multi-channel form extending radially from the ring and hingedly connected thereto. A simple method is provided for manufacturing the bag with the form unit insert.

Abstract: The invention relates to a new economical and simple process, using a new intermediate compound, for the production of 3'-substituted 7-amino-3-propenyl-4-cephem-carboxylic acid derivatives of formula ##STR1## wherein R is hydrogen, a negative charge or a silyl protecting group, R.sub.o is hydrogen or methoxy, R.sub.1 is hydrogen or a silyl protecting group and X is the radical of a nucleophile, and their acid addition salts.

Abstract: Novel amidine salts of 7-Amino-3-hydroxymethyl-3-cephem-4-carboxylic acid (=HACA), particular guanidine and diaza-bicyclo-alkylene salts, are useful as intermediates in the synthesis of cephalosporins.

Abstract: Compounds of structure: ##STR1## as well as their pharmaceutically-acceptable salts and biohydrolyzables esters, and hydrates thereof, are effective antiinfective agents, useful in treating and preventing infection.

Abstract: A process for the manufacture of 7-acylamino-3-hydroxy-cephem-4-carboxylate-1-oxide in E-rotamer form (Formula III), comprises reacting a 7-acylamino-3-exomethylenecepham-4-carboxylate-1-oxide with ozone in an inert organic solvent in the presence of a catalytic amount of an organic or inorganic base at a temperature ranging from about -80.degree. C. to about +20.degree. C. The E-rotamer (wherein the 3-hydroxy group is strongly hydrogen bonded to the carbonyl of the 4-ester group) exhibits different chemical and physical properties from and is more thermodynamically stable than, the Z-rotamer (wherein there is no hydrogen bonding between the 3-hydroxy group and the carbonyl of the 4-ester group).

Abstract: Derivatives of 7-alkylidene cephalosporanic acid sulfone and the pharmaceutically active salts thereof are found to be potent inhibitors of .beta.-lactamase enzymes.

Abstract: .beta.-lactam antibiotics of formula (I) or a salt thereof, wherein R.sup.1 is hydrogen, methoxy of formamido; R.sup.2 is an acyl group, in particular that of an antibacterially active cephalosporin; CO.sub.2 R.sup.3 is a carboxy group or a carboxylate anion, or R.sup.3 is a readily removable carboxy protecting group (such as a pharmaceutically acceptable in vivo hydrolysable ester group); R.sup.4 represents up to four substituents selected from alkyl, alkenyl, alkynyl, alkoxy, hydroxy, halogen, amino, alkylamino, acylamino, dialkylamino, CO.sub.2 R, CONR.sub.2, SO.sub.2 NR.sub.2 (where R is hydrogen or C.sub.1-6 alkyl), aryl and heterocyclyl, which may be the same or different and wherein any R.sup.4 alkyl substituent is optionally substituted by any other R.sup.4 substituent; X is S, SO, SO.sub.2, O or CH.sub.2 ; Y is S, SO or SO.sub.2 ; and m is 1 or 2, useful in the treatment of bacterial infections in humans and animals.

Abstract: Cephalosporins with an exocyclic allene in the 7-position and their pharmaceutically active salts are potent inhibitors of .beta.-lactamases and are therefore useful in the treatment of penicillin resistant infections.

Abstract: Antimicrobial quinolonyl lactam compounds comprising a lactam-containing moiety linked to a quinolone moiety, of the formula: ##STR1## wherein (1) A.sup.1, A.sup.2, A.sup.3, R.sup.1, and R.sup.4 generally form any of a variety of quinolone, naphthyridine or related cyclic moieties known in the art to have antimicrobial activity; and(2) R.sup.6 is part of a linking moiety, linking the quinolone moiety to a lactam-containing moiety having the formula: ##STR2## wherein (3) R.sup.10, R.sup.11, R.sup.12, R.sup.13, and R.sup.

Abstract: The present invention relates to compounds of the formula ##STR1## wherein R.sup.1 is an acyl group derived from a carboxylic acid, hydrogen, or an amino protecting group;R.sup.2 is hydrogen, hydroxy, lower alkyl-Q.sub.p -, cycloalkyl, lower alkoxy, lower alkenyl, cycloalkenyl, lower alkynyl, aralkyl-Q.sub.p -, aryl-Q.sub.p -, aryloxy, aralkoxy or a heterocyclic ring, the lower alkyl, cycloalkyl, lower alkoxy, lower alkenyl, cycloalkenyl, lower alkynyl, aralkyl, aryl, aryloxy, aralkoxy and the heterocyclic ring being unsubstituted or substituted with at least one group selected from carboxy, amino, nitro, oxo, cycloalkyl, cyano, lower alkyl, lower alkoxy, hydroxy, halogen, --CONR.sup.4 R.sup.5, --N(R.sup.5)COOR.sup.9, R.sup.5 CO--, R.sup.5 OCO-- or R.sup.5 COO-- where R.sup.4 is hydrogen, lower alkyl, or cycloalkyl; R.sup.5 is hydrogen or lower alkyl; R.sup.9 is lower alkyl, lower alkenyl or a carboxylic acid protecting group;Q is --CO-- or --SO.sub.

Abstract: Chromogenic and fluorogenic substrates for .beta.-lactamase, methods for synthesis thereof and methods for detecting .beta.-lactamase in a sample are provided. The substrates are substantially colorless or substantially nonfluorescent .beta.-lactam compounds which include an electronegative leaving group. The leaving group comprises a carbamate, carbonate, thiocarbamate or thiocarbonate linkage and a fluorescent moiety or a moiety capable of producing a visually detectable colored product. Upon cleavage of the lactam ring by .beta.-lactamase, the leaving group is liberated and fluorescence or a colored product is produced.

Abstract: This invention relates to 2-[(substituted)methylene]cephalosporin sulfones and in particular 2-[(heteroaryl substituted)methylene]cephalosporin sulfones which are effective elastase inhibitors as well as effective thrombin inhibitors and therefore are useful as anti-inflammatory, anti-degenerative and anti-thrombin agents.

Abstract: Cephalosporin compounds having a 3-position substituent of the formula (I) are described:--CH.sub.2 --S--Q--(Y).sub.n --Pwherein Q is a 5- or 6-membered heterocyclic ring, P is a benzene ring substituted by groups R.sup.1 and R.sup.2 which are ortho with respect to one another, wherein R.sup.1 is hydroxy or an in vivo hydrolysable ester thereof and R.sup.2 is hydroxy, an in vivo hydrolysable ester thereof, carboxy, sulpho, hydroxymethyl, methanesulphonamido or ureidos; or P is a group of the formula (II) or (III): ##STR1## wherein M is oxygen or a group NR.sup.3 wherein R.sup.3 is hydrogen or C.sub.1-4 alkyl; said ring P being further optionally substituted; and --(Y).sub.n -- is a bond or various linking groups or --(Y)--.sub.n may be such so that rings Q and P are fused.The use of such compounds as antibacterial agents is described as are processes for their preparation and intermediates therefor.

Abstract: A process for the manufacture of 7-acylamino-3-hydroxycephem-4-carboxylate-1-oxide in E-rotamer form (Formula III), comprises reacting a 7-acylamino-3-exomethylenecepham-4-carboxylate-1-oxide with ozone in an inert organic solvent in the presence of a catalytic amount of an organic or inorganic base at a temperature ranging from about -80.degree. C. to about +20.degree. C. The E-rotamer (wherein the 3-hydroxy group is strongly hydrogen bonded to the carbonyl of the 4-ester group) exhibits different chemical and physical properties from and is more thermodynamically stable than, the Z-rotamer (wherein there is no hydrogen bonding between the 3-hydroxy group and the carbonyl of the 4-ester group).

Abstract: A compound selected from the group consisting of a syn isomer of a compound of the formula ##STR1## in the R or S form or in the form of an R, S mixture wherein R.sub.1, Rc, Rb, A and A' are defined as in the following specification and their non-toxic, pharmaceutically acceptable acid addition salts having anti-bacterial activity.

Abstract: A compound selected from the group consisting of a compound of the formula ##STR1## wherein R is selected from the group consisting of ##STR2## and R.sub.b --NH--, Ra is an organic radical, Ri and Rj are individually selected from the group consisting of hydrogen, aliphatic hydrocarbon, aromatic hydrocarbon and heterocycle or taken together with the nitrogen atom to which they are attached form an optionally substituted ring, Rb is selected from the group consisting of carbocyclic aryl and heterocyclic aryl, both optionally substituted, R.sub.1A is selected from the group consisting of ##STR3## R.sub.A ' and R.sub.B ' are individually selected from the group consisting of hydrogen and alkyl of 1 to 4 carbon atoms, Z.sub.A is selected from the group consisting of a simple bond, --O-- and optionally oxidize sulfur, R.sub.

Abstract: The invention relates to a compound of the formula: ##STR1## of antimicrobial activity.

Abstract: New substituted cephalosporin sulfones are found to be potent elastase inhibitors and thereby useful anti-inflammatory/antidegenerative agents.

Abstract: There is described a process for the manufacture of carboxylic acid amides by acylating amines with 2-benzothiazolyl thioesters of carboxylic acids, which process comprises reacting the amine in the form of an acid addition salt. This process is especially of great advantage when the amine is not particularly stable in the form of the free base, which is frequently the case especially with 7-aminocephalosporin derivatives. 7-Acylamino-cephalosporin derivatives can be manufactured in good yield and in high purity with the novel process.

Abstract: There are provided compounds I ##STR1## wherein A is a hydrogen atom or an organic group,R.sub.1 is hydrogen or halogen atom or an organic group,R.sub.2 is hydrogen or halogen atom, C.sub.1 -C.sub.4 alkyl or acyloxy group,R.sub.3 is hydrogen atom, C.sub.1 -C.sub.4 alkyl or alkoxy, benzyl group or a methylene andR.sub.4 is chloro, fluoro, hydrogen atom or an organic group.The compounds I are elastase inhibitors. A process for their preparation is also provided, as are pharmaceutical compositions containing them.

Abstract: A process for the conversion of a 4-chlorosulfonyl azetidinone (a) to a 3-hydroxy-3-cephem-sulfoxide ester (d) by subjecting an intermediate comprising a tin containing Lewis acid-type Fiedel-Crafts catalyst and 3-exomethylene cepham to ozonolysis.

Abstract: Cephalosporin compounds having a 3-position substituent of the formula (I) are described,--CH.sub.2 --Y--Q (I)wherein Y is a bond or a linking group --NR.sup.4 --Y'--, --O--Y'--, --S--Y'-- wherein R.sup.4 is hydrogen, various optionally substituted alkyl groups, alkenyl, alkanoyl or alkanesulphonyl, and Y' is a bond or various optionally substituted alkylene groups; and Q is a benzene ring (optionally fused to a further benzene ring so forming a naphthyl group or optionally fused to a 5 or 6 membered heterocyclic aromatic group containing 1, 2 or 3 heteroatoms selected from nitrogen, oxygen and sulphur), said benzene ring being substituted by groups R.sup.1 and R.sup.2 which are ortho with respect to one another, wherein R.sup.1 is hydroxy or an in vivo hydrolysable ester thereof and R.sup.2 is hydroxy, an in vivo hydrolysable ester thereof, carboxy, sulpho, hydroxymethyl, methanesulphonamido or ureido; or Q is a group of the formula (II) or (III): ##STR1## wherein M is oxygen or a group NR.sup.3 wherein R.

Abstract: There are presented antibacterial cephalosporine having broad antimicrobial activity, having the formula ##STR1## wherein R is hydrogen or a carboxylic acid-protecting group: R.sub.1 represents a substituted piperazinyl group of formula ##STR2## or a substituted pyrrolidinylamino group of formula ##STR3## or a substituted pyrrolidinylmethylamino group of formula ##STR4## where the piperazinyl or pyrrolidinyl group may be optionally substituted with one or more lower alkyl groups, and where Q represents a substituted quinolinyl or naphthyridinyl group: R.sub.2 is selected from the group consisting of hydrogen, lower alkoxy, lower alkylthio and amido; R.sub.3 is hydrogen or an acyl group: and m is 0, 1 or 2, but preferably 0; as well as the corresponding readily hydrolyzable esters. pharmaceutically acceptable salts and hydrates of these compounds.

Abstract: There are presented antibacterial cephalosporins having broad antimicrobial activity as well as intermediates for their formation, such compounds having the formula ##STR1## wherein R is hydrogen or a carboxylic acid-protecting group; R.sub.1 is a substituted piperazinium group of the formula ##STR2## in which Q represents a substituted quinolinyl or naphthyridinyl group and the piperazine nucleus may be optionally substituted with one or more lower alkyl groups; R.sub.2 is selected from the group consisting of hydrogen, lower alkoxy, lower alkylthio and amido; R.sub.3 is hydrogen or an acyl group; and m is 0, 1 or 2, preferably 0;as well as the corresponding readily hydrolyzable esters, pharmaceutically acceptable salts and hydrates of these compounds.

Abstract: A method for synthesizing .DELTA..sup.3 -7-substituted amino desacetoxy cephalosporanic acid from a penicillin sulfoxide or its alkylsilylated ester derivative is provided. According to the method, penicillin sulfoxide is heated in the presence of an organic ammonium salt catalyst and a copolymer composed of dimethylsilane and urea units until formation of the cephalosporanic acid occurs by ring expansion reaction. The copolymer functions both as a dehydrating agent for removing the water by-product generated from the reaction as well as an esterifying agent for converting penicillin sulfoxide into its dimethylsilyl ester derivative. The method of the invention produces high yields of the cephalosporanic acid and avoids the need for excess dimethylsilyating agents.

Abstract: 7 .alpha.-formamido cephalosporin derivatives having a 3[N-(optionally substituted)aminothiopyridinium thiomethyl] substituent have anti-bacterial activity and are of use in anti-bacterial therapy. Processes for the preparation thereof and intermediates for use in these processes are also disclosed.