Abstract: Provided herein is a method for the synthesis of cephalosporin antibiotic compounds comprising the conversion of a protected 7-amino group into a 7-carboxamide moiety in a single step.

Abstract: It is an object of the present invention to provide antimicrobial metallodrugs comprising an antimicrobial peptide (“AMP”) and/or an antibiotic covalently bound to a metal binding moiety. These metallodrugs combine a metal binding domain which typically catalyzes oxido-reductase chemistry or acts as a Lewis-Acid catalyst, with a member of a diverse class of antimicrobial agents currently validated in preclinical and clinical settings for the treatment of a broad spectrum of pathogenic organisms.

Abstract: Broad spectrum beta-lactamase inhibitors. Certain inhibitors also exhibit potent antibiotic activity in addition to beta-lactamase inhibition. Compounds of the invention are designed such that on cleavage of the beta-lactam ring reactive moieties are generated which can inactivate beta-lactamase. Also provided are methods of making beta-lactamase inhibitors and beta-lactam antibiotics exhibiting such inhibition. Additionally provided are pharmaceutical compositions for treatment or prevention of bacterial infections and methods of treatment of such infections.

Abstract: Provided herein is a method for the synthesis of cephalosporin antibiotic compounds comprising the conversion of a protected 7-amino group into a 7-carboxamide moiety in a single step.

Abstract: The present invention provides novel cephalosporin derivatives of formula I, their analogues, their use for the treatment of infections in mammals, pharmaceutical composition containing these novel compounds, and methods for the preparation of these compounds.

Abstract: Cefodroxil monohydrate is formed by a processing which includes a) bringing an aqueous solution of cefadroxil monohydrate to a pH of between 7 to 9 with a suitable titrant; b) lowering the pH to a value of between 5 and 6.5 to obtain a suspension of cefadroxil monohydrate in crystal form; and c) isolating the cefadroxil monohydrate in crystal form from the suspension obtained in step b). The cefadroxil monohydrate thereby obtained exhibits a CIE b value of below 6, and advantageously a CIE b value of below 12 when stored at a temperature of 25° C. for at least 1 month.

Abstract: It is an object of the present invention to provide antimicrobial metallodrugs comprising an antimicrobial peptide (“AMP”) and/or an antibiotic covalently bound to a metal binding moiety. These metallodrugs combine a metal binding domain which typically catalyzes oxido-reductase chemistry or acts as a Lewis-Acid catalyst, with a member of a diverse class of antimicrobial agents currently validated in preclinical and clinical settings for the treatment of a broad spectrum of pathogenic organisms.

Abstract: The present invention relates to a process for the preparation of cefadroxil in crystal form, comprising a) adding an aqueous solution of cefadroxil to a crystallization vessel and a titrant to keep a pH in the crystallization vessel of between 7 to 9; and b) lowering the pH in the crystallization vessel to a value of between 5 and 6.5 to obtain a suspension of the ?-lactam compound in crystal form. The invention further relates to cefadroxil in crystal form obtainable by the process according to the present invention. The invention also relates to cefadroxil in crystal form with a CIE b value of below 12 when stored at a temperature of 25° C. for at least 1 month.

Abstract: The present invention relates to compounds that are substrates for an enzyme, and upon reaction with the enzyme provide a detectable response, such as an optically detectable response. In particular, the compounds have utility in detecting the presence of a ?-lactamase in a sample. In addition to the compounds, methods are disclosed for analyzing a sample for the presence of a ?-lactmase, for example, as an indicator of expression of a nucleic acid sequence including a sequence coding for a ?-lactmase. Kits are disclosed that include the disclosed compounds and additional components, for example, cells, antibodies, a ?-lactmase or instructions for using the components in an assay.

Abstract: The present invention relates to cephalosporin derivatives having ?-lactamase inhibitory activity. The compounds are useful in preventing or treating bacterial resistance to an antibiotic, e.g. a ?-lactam antibiotic. Disclosed herein are compounds that are inhibitors of class B metallo-?-lactamases, as well as class A, C, and D serine ?-lactamases. In some preferred embodiments, the compounds are 3?-thiobenzoate derivatives of a cephalosporin. Pharmaceutical compositions, methods, uses, kits and commercial packages comprising the compounds are also disclosed.

Abstract: Example solar cells and methods for making and using the same are disclosed. An example solar cell may include an electron conductor layer, a quantum dot layer, a bifunctional ligand layer coupling the electron conductor layer and the quantum dot layer, and a hole conductor layer coupled to the quantum dot layer. The bifunctional ligand layer may include an antibiotic, and in some cases, a cephalosporin-based antibiotic.

Abstract: An intermediate compound represented by formula (IV) as follows:

Abstract: The present invention relates to a process for the preparation of cefadroxil in crystal form, comprising a) adding an aqueous solution of cefadroxil to a crystallisation vessel and a titrant to keep a pH in the crystallisation vessel of between 7 to 9; and b) lowering the pH in the crystallisation vessel to a value of between 5 and 6.5 to obtain a suspension of the ?-lactam compound in crystal form. The invention further relates to cefadroxil in crystal form obtainable by the process according to the present invention. The invention also relates to cefadroxil in crystal form with a CIE b value of below 12 when stored at a temperature of 25° C. for at least 1 month.

Abstract: The present invention describes a process for preparing cephradine, said process comprising reacting 7-aminodesacetoxy cephalosporanic acid (7-ADCA) with D-dihydrophenylglycine in activated form (DHa) in the presence of an enzyme in a reaction mixture to form cephradine, resulting in a conversion of 7-ADCA into cephradine of at least 70%, wherein the concentration D-dihydrophenylglycine (DH) in the reaction mixture is below 2 wt.%, wherein the conversion of 7-ADCA into cephradine & equals; (nCEF/n7-ADCA)*100%, wherein nCEF=quantity of cephradine formed (in mole); and n7-ADCA=total quantity of 7-ADCA added to reaction mixture (in mole).

Abstract: Provided is a process for preparing a compound of formula 1 or its salt, which includes reacting a compound of formula 2 with a compound of formula 3 in the presence of a base.

Abstract: Provided is a process for preparing a compound of formula 1 or its salt, which includes reacting a compound of formula 2 with a compound of formula 3 in the presence of a base.

Abstract: The present invention relates to a process for preparing a key intermediate of cefprozil and use of this intermediate in the preparation of cefprozil thereby avoiding impurity-causing self-acylation. [R-(Z)]-[4-hydroxy-?-[(3-methoxy-1-methyl-3-oxo-1-propenyl)amino]]benzeneacetic acid, mono potassium salt is reacted with ethyl chloroformate to obtain mixed anhydride which is then silylated with N,O-bis(trimethylsilyl)acetamide. The silylated compound obtained is reacted with [7-trimethylsilylamino-3-(Z/E-propen-1-yl)-3-cephem-4-carboxylic acid]trimethylsilyl ester and deprotected with aqueous hydrochloric acid to give cefprozil.

Abstract: There is provided a process for the preparation of a compound according to Formula (II): which includes the step of cyclizing a compound of Formula (III): wherein R1, R2, R3, R4, X and m have meanings which are given in the description.

Abstract: A process for the preparation of 3-methylcepham-4-carboxylate of the formula (I). wherein R2 and R3 may be same or different and represent hydrogen, halogen, amino, alkyl, phenacetamido, substituted acetamido, phthalimido with a proviso that both R2 and R3 are not NH2, phenacetamido, phthalimido and the like; R1 represents a lower alkyl, p-methoxybenzyl, p-nitrobenzyl, o-nitrobenzyl, o-methoxybenzyl, o-chlorobenzyl or diphenylmethyl group, or a suitable ester residue which can be deprotected at a latter stage, L represents a leaving group; which comprises cyclizing the compound of formula (III) using a cyclizing agent in the presence of organic or inorganic nitrites and a solvent at a temperature in the range of ?40° C. to +60° C. to obtain compound of formula (I).

Abstract: The invention relates to a process for the preparation of cephalexin with the aid of a penicillin amidase immobilized on a crosslinked hydrophilic copolymer which has binding activity for ligands having nucleophilic groups and is in bead form.

Abstract: There is provided a process for the preparation of a compound according to Formula (II): which includes the step of cyclising a compound of Formula (III): wherein R1, R2, R3, R4, X and m have meanings which are given in the description.

Abstract: The present invention relates to novel processes for the preparation of 3-methylenecephams. More specifically, the present invention relates to the intramolecular cyclization of penicillin sulfoxide derived monocyclic azetidinone derivatives with organometallic catalysts of the formula III. MEx(H2O)y  (III) wherein: M is Sc, Y, La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, Lu, Zr, Hf, Th, Nb, Ta, U, Bi, or In; E is O[SO2(C1-C6 polyfluoroalkyl)], N[SO2(C1-C6 polyfluoroalkyl)]2, or C[SO2(C1-C6 polyfluoroalkyl)]3; x is 3; y is 0, 1, 2, 3, 4, 5, 6, 7, 8, or 9.

Abstract: 7-amino-3-methoxymethyl-3-cephem-4-carboxylic acid of formula (I) can be easily prepared by reacting 7-aminocephalosporanic acid of formula (II) with an azeotropic mixture of trimethyl borate and methanol in the presence of methanesulfonic acid:

Abstract: A process for the preparation of Cefuroxime acid (I), which comprises the following steps: (1) Extraction of deacetyl 7-glutaryl ACA (II) aqueous solution at acid pH with organic solvents (for example according to the procedures disclosed in U.S. Pat. No. 5,801,241); (2) drying the resulting solution while preventing lactonization of the intermediate; (3) carbamoylation of the hydroxymethyl group at the 3-position by reaction with chlorosulfonyl isocyanate or similar products; (7) extraction of the carbamoyl derivative from step 3 with water at neutral pH; (8) enzymatic hydrolysis of the amide at the 7-position of the cephalosporanic ring with glutaryl acylase; (6) acylation of the amnino group by condensation with 2-furanyl(sin-methoxyimino)acetic acid chloride or mixed anhydride.

Abstract: Processes for preparing compounds having two or three antibiotic functionalities using quinolone derivatives, &bgr;-lactams and vancomycin and the like as the starting materials and chloride linking agents; and the novel compounds prepared by these processes, are disclosed.

Abstract: A process for preparing a 3-cephem compound represented by the formula (3), the process comprising the steps of reacting a &bgr;-lactam compound represented by the formula (1) with a phosphorus halide compound in the presence of an organic base to give an imino-&bgr;-lactam compound represented by the formula (2), adding a phenol to the same reaction system to cause decomposition due to reaction with an alcohol and simultaneously to remove the protection of carboxylic acid ester, giving a 3-cephem compound represented by the formula (3) or a salt thereof where R1, R2, R3 and X are as defined above.

Abstract: The invention provides compounds of formula I and IV: wherein R1-R11 and A have any of the values defined in the specification, and their pharmaceutically acceptable salts, are useful for inhibiting &bgr;-lactamase enzymes, for enhancing the activity of &bgr;-lactam antibiotics, and for treating &bgr;-lactam resistant bacterial infections in a mammal. The invention also provides pharmaceutical compositions, processes for preparing compounds of formula I and IV, and novel intermediates useful for the synthesis of compounds of formula I and IV. The A can be, for example, thio, sulfinyl, or sulfonyl.

Abstract: A method for preparing crystalline cefadroxil hemihydrate from cefadroxil dimethyl formamide solvate using a mixture of a lower alkanol and water.

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: A process for preparing halogenated &bgr;-lactam compounds, characterized in that a &bgr;-lactam amino compound of the formula (1) is reacted with nitrous acid or nitrite in a slurry dispersion state in water, under acid condition in the presence of halogen molecules, thereby obtaining a halogenated &bgr;-lactam compound of the formula (4) wherein n is an integer of 0 to 2; A is the formula (2) or (3); R1 and R2 are the same or different and are hydrogen atom, halogen atom, C1˜C3 alkyl group, C2˜C4 alkenyl group, C2˜C4 alkynyl group, nucleophilic group, or CH2R3; and R3 is halogen atom or nucleophilic group  wherein A is as defined above; X1 is hydrogen atom or halogen atom; and X2 is halogen atom.

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: A method for preparing an &agr;-oxolactam comprising, reacting a corresponding &agr;-diazolactam with an oxygen donor, in the presence of a transition metal catalyst, to yield the corresponding &agr;-oxolactam.

Abstract: The present invention provides substituted amino bicyclic-&bgr;-lactam penam derivatives and substituted amino bicyclic-&bgr;-lactam cepham derivatives and their diastereoisomers of formula I, as well as compositions, methods of making, and methods of using, which exhibit excellent cysteine protease inhibitory activity and which may be used for treatment of different diseases such as cancer (including cancer metastasis), osteoporosis, rheumatoid arthritis.

Abstract: The present invention relates to novel substituted pyridines/pyrimidines of the formula I where A is CH or N; X is NH, oxygen or S(O)q where q is 0, 1 or 2; Y is a direct bond or CH2; Z is oxygen, NR7 or S(O)m is 0, 1 or 2, and the radicals R1, R2, R3, R4, R5, R6 and R7 are as defined in the description, to processes for their preparation, and to their use as pesticides, fungicides, ovicides or as veterinary medicaments.

Abstract: The subject matter of the present invention relates to a reagent and a process useful for cleaving a functional group protected by an alkoxycarbonyl group during an organic synthesis. This reagent comprises: a) an aqueous phase; b) a catalyst comprising at least one group VIII element in the periodic table of elements and at least one water-soluble ligand, wherein the group VIII element in the periodic table is maintained in the aqueous phase by the formation of a complex with at least one water-soluble ligand; and c) a nucleophilic compound soluble in the aqueous phase; and optionally d) an organic phase.

Abstract: A phloroglucide derivative having the following formula: ##STR1## wherein Q is halogen; X is CH.sub.2 or C.dbd.O; Y is cephalosporin having a formula of ##STR2## wherein Ph is phenyl, Ac is acetoxy, or pharmaceutically acceptable salts thereof, and an antibacterial pharmaceutical composition derived thereof.

Abstract: Process for purifying 7-substituted aminodeacetoxycephalosporins through the use of filter membranes. A process for purification by ultrafiltration and/or nanofiltration with a cut-off for molecular weights over 10,000 Dalton and preferably over 2000 Dalton is described. For example cephalosporin-G of increased purity, represented by a 6-8% increase in the HPLC titre, with a reduction of 50% in absorbance, is obtained using this technique. The invention makes it possible for the purified products to be used directly in the synthesis of other antibiotic compounds without the need for intermediate isolation.

Abstract: A compound having the following general formula (I): ##STR1## where R is a hydrogen atom; a linear or branched C.sub.1 -C.sub.4 alkyl group, unsubstituted or substituted by at least a phenyl group or at least a hydrogen atom; a benzyl group substituted by at least a linear or branched C.sub.1 -C.sub.4 alkyl or alkoxy group or a nitro group; a silyl substituted by at least a linear or branched, unsubstituted or substituted C.sub.1 -C.sub.4 alkyl group; n is 0 or 1; and Y is a radical of formula ##STR2## wherein A is H, OH, Cl, CH.sub.2, CH.sub.2 X, where X is F, Cl, Br, I, OH or OR' and R' is COCH.sub.3 or a linear or branched, unsubstituted or substituted C.sub.1 -C.sub.4 alkyl group and - - - represents a single or a double bond, with the proviso that when n=0 and R is H, R' is not a methyl group.

Abstract: An industrially excellent, novel process for producing cephem compounds which are useful as medicines, particularly, antibiotics and represented by the following formula (III): ##STR1## wherein R.sup.1 means either group represented by the following formula: ##STR2## R.sup.2 denotes a carboxyl group or a carboxyl anion, and R.sup.3 stands for a lower alkyl group, a halogen atom, a lower alkyl group substituted by an aliphatic acyloxy group having 1-6 carbon atoms, or any one of the groups represented by the following formulae: ##STR3## which comprises reacting in water a 3-cephem-4-carboxylate represented by the following formula (I): ##STR4## or a salt thereof with an acid chloride represented by the formula (II), R.sup.1 COCl.

Abstract: The present invention is concerned with a chemical acetylation process for the preparation of 3'-acetylated cephalosporin from desacetyl-cephalosporin. The novel process is carried out with an acetyl donor and an activator or catalyst.

Abstract: A process for the manufacture of the antibiotic 7-(D-.alpha.-amino-.alpha.-phenylacetamido)-3-methyl-3-cephem-4-carboxylic acid (cephalexin) and pharmaceutically acceptable salts thereof. It consists of reacting an enamine protected potassium salt of D-(-)-.alpha.-phenyl glycine (Dane salt) with an acid chloride in a twin solvent mixture in the presence of a pyridine derived twin catalytic mixture at -20 to -65.degree. C. The resulting mixed anhydride is condensed with an alkyl guanidinium salt solution of 7-amino desacetoxy cephalosporanic acid (7-ADCA) at -10.degree. C. to -65.degree. C. followed by hydrolytic cleavage of the enamine derivative of the resulting compound with an aqueous mineral acid and precipitation of the antibiotic in the presence of an alcohol as co-solvent. If desired the cephalexin is converted into its pharmaceutically acceptable salts in a known manner.

Abstract: The disclosed process is for the recovery of cephalexin from a mixture containing cephalexin and 7-aminodesacetoxy cephalosporanic acid (7-ADCA), wherein a mixture of cephalexin and 7-ADCA, with a pH higher than 7, which apart from any solid cephalexin being present is homogeneous at a pH between 7 and 8.5, is subjected to a pH modification until a pH lower than 7.8 is reached, and the solid substance is recovered. The disclosed process is particularly suited for application to a reaction mixture obtained after the enzymatic acylation reaction of 7-ADCA with a phenylglycine derivative as an acylation agent. Pure cephalexin can thus be recovered in a simple manner.

Abstract: The invention relates to a new process for the depletion of 7-amino-3-?(E)-1-propen-1-yl!-3-cephem-4-carboxylic acid in mixtures of 7-amino-3-?(Z)-1-propen-1-yl!-3-cephem-4-carboxylic acid and 7-amino-3-?(E)-1-propen-1-yl!-3-cephem-4 carboxylic acid, by means of the crystalline hydrochloride or a metal or amine salt of 7-amino-3-?(Z/E)-1-propen-1-yl!-3-cephem-4-carboxylic acid or by adsorption chromatography.

Abstract: The subject matter of the present invention relates to a reagent and a process useful for cleaving a functional group protected by an alkoxycarbonyl group during an organic synthesis. This reagent comprises: a) an aqueous phase; b) a catalyst comprising at least one group VIII element in the periodic table of elements and at least one water-soluble ligand, wherein the group VIII element in the periodic table is maintained in the aqueous phase by the formation of a complex with at least one water-soluble ligand; and c) a nucleophilic compound soluble in the aqueous phase; and optionally d) an organic phase.

Abstract: A process is described for preparing 3-exomethylene cephalosporanic acid derivatives for use in the synthesis of cephalosporin antibiotics such as ceftibuten. The process comprises electrochemical reduction of a compound of the formula (IV) ##STR1## wherein: R.sup.3 is ##STR2## is an optional sulfoxide group; n is 2 or 3; R.sup.1 is H and R is H or NHR.sup.2, where R.sup.2 is H or a protecting group selected from C.sub.6 H.sub.5 CH.sub.2 OC(O)--, C.sub.6 H.sub.5 C(O)-- or C.sub.1 -C.sub.6 alkoxy-C(O)--; or wherein R and R.sup.1 together with the carbon atom to which they are attached comprise --C(O)--, and produces the desired 3-exomethylene compounds with low levels of the corresponding 3-methyl tautomers.

Abstract: The cephalosporin intermediates, desacetyl 7-glutaryl ACA and desacetyl cephalosporin D, are obtained in the form of a concentrated aqueous solution from an aqueous solution containing said intermediates in less concentrated form by solvent extraction using cyclohexanone followed by back-extraction into water. The concentrated aqueous solution of intermediate is in a form which can be used for economical production of 7-ACA using known procedures.

Abstract: The present invention relates to the use of 7-alkylidene derivatives of cephalosporin esters, such as sulfides, sulfoxides, and sulfones, as inhibitors of human leukocyte elastase. These materials are therefore useful as anti-inflammatory and anti-degenerative agents.

Abstract: There are disclosed new compounds of formula (I), wherein R is: a hydrogen atom: a linear or branched C1-C4 alkyl group, unsubstituted or substituted by at least a phenyl group or at least a hydrogen atom: a benzyl group substituted by at least a linear or branched C1-C4 alkyl or alkoxy group or a nitro group; a silyl substituted by at least a linear or branched, unsubstituted or substituted C1-C4 alkyl group; n is 0 or 1; and Y is a radical of formula (II), wherein A is H, OH, Cl, CH2, CH2X, where X is F, Cl, Br, I, OH or OR' and R' is COCH3 or a linear or branched, unsubstituted or substituted C1-C4 alkyl group and . . . represents a single or a double bond, with the proviso that when n=0 and R is H, R' is not a methyl group; and processes for obtaining them.

Abstract: An object of the invention is to provide a process for preparing a 3-substituted cephem compound from an allenyl-.beta.-lactam compound which can be easily produced from an inexpensive penicillin compound by a simple reaction procedure.The process of the invention comprises reacting an allenyl-.beta.-lactam compound with an organohalogen compound in the presence of a metal having a standard oxidation-reduction potential of -0.3 (V/SCE) or less in an amount at least equimolar with the allenyl-.beta.-lactam compound and 0.0001 to 0.5 mole, per mole of the allenyl-.beta.-lactam compound, of a metal compound having a higher standard oxidation-reduction potential than said metal.

Abstract: The present invention relates to a novel process for preparing ceftaroline fosamil as well as to intermediates of this process.