Abstract: The present invention relates to an improved process for oxidizing 3-hydroxy-methyl-cephem derivatives to the corresponding 3-formyl-cephem derivatives. In particular this oxidation process is for the preparation of 7-[2-(5-amino-[1,2,4]thia-diazol-3-yl)-2-hydroxyimino-acetylamino]-3-formyl-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid derivatives of formula (I) using a combination of a hypervalent iodine oxidizing agent of the type 10-I-3 such as bis(acetoxy)iodo-benzene (BAIB) and a catalyst such as 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO). These compounds of formula (I) are intermediates in the synthesis of ceftobiprole.

Abstract: The present invention relates to a method for the production of organic compounds, in particular sodium (6R,7R)-7-[(Z)-2-(5-amino-[1,2,4]thiadiazol-3-yl)-2-hydroxyimino-acetylamino]-8-oxo-3-[(E)-(R)-1?-(5-methyl-2-oxo-[1,3]-dioxol-4-ylmethoxycarbonyl)-2-oxo-[1,3?]bipyrrolidinyl-3-ylidenemethyl]-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylate (ceftobiprole medocaril), and compounds of the general formula (1) and of the general formula (2), the compounds themselves and intermediates in the production according to the invention.

Abstract: The present invention provides a process for producing silylated pullulan, which features reacting pullulan with N,O-bistrimethylsilylacetamide by using, as a reaction medium, only one of N-methyl-2-pyrrolidone and N-ethyl-2-pyrrolidone or a mixed solvent of both of them. Compared with conventional processes, the process according to the present invention can produce high-purity silylated pullulan simply, easily and efficiency.

Abstract: The present invention relates to a method for the production of organic compounds, in particular sodium (6R,7R)-7-[(Z)-2-(5-amino-[1,2,4]thiadiazol-3-yl)-2-hydroxyimino-acetylamino]-8-oxo-3-[(E)-(R)-1?-(5-methyl-2-oxo-[1,3]-dioxol-4-ylmethoxycarbonyl)-2-oxo-[1,3?]bipyrrolidinyl-3-ylidenemethyl]-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylate (ceftobiprole medocaril), and compounds of the general formula (1) and of the general formula (2), the compounds themselves and intermediates in the production according to the invention.

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: 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: 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. Compounds of the invention include those of formula: and pharmacologically acceptable salts thereof where variables Z, Y, M, y, n, R, R4, R5, R1 and R2 are as defined in the specification. M most generally represents a chemical moiety which is in conjugation with the nitrogen of the core beta-lactam ring system of the compound, such that one or more reactive species, e.g., electrophilic or nucleophilic sites are generated on modification of M which is initiated by cleavage of the beta-lactam ring. Also provided are methods of making beta-lactamase inhibitors and beta-lactam antibiotics exhibiting such inhibition.

Abstract: A solid DMSO solvate of a compound of formula (I) is described, which is a useful intermediate for preparing the broad spectrum antibiotics Ceftobiprole and Ceftobiprole Medocaril.

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 ?-lactamase, for example, as an indicator of expression of a nucleic acid sequence including a sequence coding for a ?-lactamase. Kits are disclosed that include the disclosed compounds and additional components, for example, cells, antibodies, a ?-lactamase or instructions for using the components in an assay.

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: 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: Pharmaceutical compositions including a cephalosporin disclosed herein as having the structure of formula (III).

Abstract: A compound represented by formula (I) or a pharmaceutically acceptable salt thereof wherein A represents a group represented by one of formulae (i)-(iii); B represents a group represented by formula (v) or (vi); and E represents a substituted or unsubstituted heterocyclic group having a cationic nitrogen atom.

Abstract: The present invention relates to cephalosporin antibacterial compounds of Formula (I): or corresponding pharmaceutically acceptable salts thereof, corresponding pharmaceutical compositions, compound preparation and treatment methods for bacterial infections, especially those caused by gram-negative bacteria.

Abstract: The present invention relates generally to methods and compounds for regulating the release of nitric oxide in the vicinity of biofilm-forming microorganisms to regulate programmed cell death in the microorganisms and thereby promote dispersal of microorganism from biofilms and/or inhibit biofilm formation or development. More particularly, the invention relates to the use of compounds to provide spatial and temporal control over nitric oxide release.

Abstract: The invention features pharmaceutically acceptable salts of cefdinir, including primary, secondary, and tertiary amine salts of cefdinir, and preparation methods, and pharmaceutical compositions including cefdinir. The invention also features water dispersible pharmaceutical dosage forms including cefdinir as active agent and methods for preparing the dosages. The invention also features tablet forms of cefixime characterized in that the tablets are in effervescent form. The invention also features the process for preparing effervescent tablet forms with cefdinir as active agents and pharmaceutical formulations obtained by the process.

Abstract: The present invention provides novel bisphosphonate conjugates, pharmaceutical compositions comprising bisphosphonate conjugates and methods of using such analogs in the treatment of bone cancer, bone-related diseases, bone infection, bone inflammation, and diseases of the soft tissues surrounding bones.

Abstract: The invention features pharmaceutically acceptable salts of cefdinir, including primary, secondary, and tertiary amine salts of cefdinir, and preparation methods, and pharmaceutical compositions including cefdinir. The invention also features water dispersible pharmaceutical dosage forms including cefdinir as active agent and methods for preparing the dosages. The invention also features tablet forms of cefixime characterized in that the tablets are in effervescent form. The invention also features the process for preparing effervescent tablet forms with cefdinir as active agents and pharmaceutical formulations obtained by the process.

Abstract: Inhibitors of the enzyme beta-lactamase are provided comprising compounds of formula (II) wherein R1 or R2 is a pyridyl group and R5 is a group of formula 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: This invention provides cross-linked glycopeptide-cephalosporin compounds and pharmaceutically acceptable salts thereof which are useful as antibiotics. This invention also provides pharmaceutical compositions containing such compounds; methods for treating bacterial infections in a mammal using such compounds; and processes and intermediates useful for preparing such compounds.

Abstract: The present invention relates to novel cephalosporin derivatives represented by Chemical Formula 1. Wherein, X, Y, L, R1, and R2 are as same as defined in the description of the invention. The present invention also relates to pharmaceutical antibiotic compositions comprising a novel celphalosporin derivative represented by Chemical Formula 1, a prodrug thereof, a hydrate thereof, a solvate thereof, an isomer thereof, or a pharmaceutically acceptable salt thereof as an effective ingredient. According to the present invention, novel cephalosporin derivatives, a prodrug thereof, a hydrate thereof, a solvate thereof, an isomer thereof, or a pharmaceutically acceptable salt thereof as an effective ingredient for the broad spectrum of antibiotic resistant, low toxicity, particularly in Gram-negative bacteria, which can be useful with strong antimicrobial activity.

Abstract: The present invention relates to a method for inhibiting the induction of cell death by inhibiting the synthesis or secretion of AGE-albumin in cells of the mononuclear phagocyte system, to an AGE-albumin synthesis inhibitor, and to a pharmaceutical composition comprising the AGE-albumin synthesis inhibitor for preventing or treating degenerative disease and autoimmune disease. The AGE-albumin of the present invention is synthesized and secreted in human microglia or human macrophages in an Alzheimer's model, stroke model, Parkinson's disease model and rheumatoid arthritis model. The AGE-albumin synthesis and secretion are caused by oxidative stress. The expression of RAGE increases in first-order human neurons or cartilage cells to which AGE-albumin is administered, whereupon a MAPK signaling pathway is activated and the expression of Bax increases to induce an increase in calcium in mitochondria, thus finally inducing cell death.

Abstract: A compound of the formula: wherein X is —N?, —CH?, or the like; W is —CH2— or the like; U is —S— or the like; R1 and R2 are each independently hydrogen, halogen, optionally substituted lower alkyl, or the like; R3 is hydrogen or the like; each R4 is independently hydrogen, halogen, or the like; m is an integer from 0 to 2; Q is a single bond, or the like; G is —C(?O)—, or the like; D is a single bond, —NH—, or the like; and E is a cyclic quaternary ammonium group, or an ester, a protected compound at the amino on the ring in the 7-side chain, a pharmaceutically acceptable salt, or a solvate thereof.

Abstract: Provided is a cephem compound which has a wide antimicrobial spectrum, and in particular exhibit potent antimicrobial activity against beta-lactamase producing Gram negative bacteria, and pharmaceutical composition comprising the same. A Compound of the formula (I): wherein W and U are as defined in the specification; R1 is as defined in the specification; R2A and R2B are as defined in the specification, provided that R2A and R2B are not taken together to form an optionally substituted oxime group when R1 is aminothiazole or aminothiadiazole optionally protected at the amino group; ring A is a benzene ring or a 6-membered aromatic heterocyclic group having 1-3 nitrogen atoms; R3 is a hydrogen atom, —OCH3 or —NH—CH(?O); k is an integer from 0 to 2; R4 is as defined in the specification; and D and E are as defined in accordance with a) or b) described in the specification.

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 an improved process for oxidizing 3-hydroxy-methyl-cephem derivatives to the corresponding 3-formyl-cephem derivatives. In particular this oxidation process is for the preparation of 7-[2-(5-amino-[1,2,4]thia-diazol-3-yl)-2-hydroxyimino-acetylamino]-3-formyl-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid derivatives of formula (I) using a combination of a hypervalent iodine oxidizing agent of the type 10-I-3 such as bis(acetoxy)iodo-benzene (BAIB) and a catalyst such as 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO). These compounds of formula (I) are intermediates in the synthesis of ceftobiprole.

Abstract: The invention features pharmaceutically acceptable salts of cefdinir, including primary, secondary, and tertiary amine salts of cefdinir, and preparation methods, and pharmaceutical compositions including cefdinir. The invention also features water dispersible pharmaceutical dosage forms including cefdinir as active agent and methods for preparing the dosages. The invention also features tablet forms of cefixime characterized in that the tablets are in effervescent form. The invention also features the process for preparing effervescent tablet forms with cefdinir as active agents and pharmaceutical formulations obtained by the process.

Abstract: A compound represented by Formula I, wherein M represents Na+, K+, NH4+, or Cs+; and 1) when Y represents SO42?: when m=1, then n=1; and when m=0.5, then n=1.5; and 2) when Y represents PO43?, when m=1, then n=2. The compound has good solubility and high bioavailability and can be formulated into oral pharmaceutical preparations and pharmaceutical preparations for injections.

Abstract: The present invention relates to novel cephalosporin derivatives represented by Chemical Formula 1. Wherein, X, Y, L, R1, and R2 are as same as defined in the description of the invention. The present invention also relates to pharmaceutical antibiotic compositions comprising a novel celphalosporin derivative represented by Chemical Formula 1, a prodrug thereof, a hydrate thereof, a solvate thereof, an isomer thereof, or a pharmaceutically acceptable salt thereof as an effective ingredient. Compounds of the present invention are effective ingredients for the broad spectrum of antibiotic resistance, exhibit low toxicity, particularly in Gram-negative bacteria, which can be useful with strong antimicrobial activity.

Abstract: The present invention relates to novel cephalosporin derivatives represented by Chemical Formula 1. Wherein, X, Y, L, R1, and R2 are as same as defined in the description of the invention. The present invention also relates to pharmaceutical antibiotic compositions comprising a novel celphalosporin derivative represented by Chemical Formula 1, a prodrug thereof, a hydrate thereof, a solvate thereof, an isomer thereof, or a pharmaceutically acceptable salt thereof as an effective ingredient. According to the present invention, novel cephalosporin derivatives, a prodrug thereof, a hydrate thereof, a solvate thereof, an isomer thereof, or a pharmaceutically acceptable salt thereof as an effective ingredient for the broad spectrum of antibiotic resistant, low toxicity, particularly in Gram-negative bacteria, which can be useful with strong antimicrobial activity.

Abstract: The present invention relates to a method for the production of organic compounds, in particular sodium (6R,7R)-7-[(Z)-2-(5-amino-[1,2,4]thiadiazol-3-yl)-2-hydroxyimino-acetylamino]-8-oxo-3-[(E)-(R)-1?-(5-methyl-2-oxo-[1,3]-dioxol-4-ylmethoxycarbonyl)-2-oxo-[1,3?]bipyrrolidinyl-3-ylidenemethyl]-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylate (ceftobiprole medocaril), and compounds of the general formula (1) and of the general formula (2), the compounds themselves and intermediates in the production according to the invention.

Abstract: The present invention relates to a method for the production of organic compounds, in particular sodium (6R,7R)-7-[(Z)-2-(5-amino-[1,2,4]thiadiazol-3-yl)-2-hydroxyimino-acetylamino]-8-oxo-3-[(E)-(R)-1?-(5-methyl-2-oxo-[1,3]-dioxol-4-ylmethoxycarbonyl)-2-oxo-[1,3?]bipyrrolidinyl-3-ylidenemethyl]-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylate (ceftobiprole medocaril), and compounds of the general formula (1) and of the general formula (2), the compounds themselves and intermediates in the production according to the invention.

Abstract: The present invention relates to cephalosporin of formula (I) in crystalline form. The compound of formula (I) in crystalline form is useful as antibiotics having potent and broad antibacterial activity; especially against methicillin resistant Staphylococci (MRSA) and Pseudomonas aeruginosa.

Abstract: Substrates for ?-lactamase of the general formula I in which one of X and Y is a fluorescent donor moiety and the other is a quencher (which may or may not re-emit); R? is selected from the group consisting of H, lower (i.e., alkyl of 1 to about 5 carbon atoms) and (CH2)nOH, in which n is 0 or an integer from 1 to 5; R? is selected from the group consisting of H, physiologically acceptable metal and ammonium cations, —CHR2OCO(CH2)nCH3, —CHR2OCOC (CH3)3, acylthiomethyl, acyloxy-alpha-benzyl, delta-butyrolactonyl, methoxycarbonyloxymethyl, phenyl, methylsulphinylmethyl, beta-morpholinoethyl, dialkylaminoethyl, acyloxyalkyl, dialkylaminocarbonyloxymethyl and aliphatic, in which R2 is selected from the group consisting of H and lower alkyl; A is selected from the group consisting of S, O, SO, SO2 and CH2; and Z? and Z? are linkers for the fluorescent donor and quencher moieties.

Abstract: High penetration compositions (HPC) of a parent compound, which are capable of crossing biological barriers with high penetration efficiency. The HPCs are capable of being converted to parent drugs or parent drug-related compounds such as metabolites after crossing one or more biological barriers and thus can render treatments for the conditions that the parent drugs or parent drug-related compounds can. Additionally, the HPCs are capable of reaching areas that their parent drugs or parent drug-related compounds may not be able to access or to render a sufficient concentration at the target areas HPCs of NSAIA, for example, have demonstrated indications such as treating hair loss. A HPC can be administered to a subject through various administration routes, e.g., locally delivered to an action site of a condition with a high concentration or systematically administered to a biological subject and enter the general circulation with a faster rate.

Abstract: This invention provides cross-linked glycopeptide—cephalosporin compounds and pharmaceutically acceptable salts thereof which are useful as antibiotics. This invention also provides pharmaceutical compositions containing such compounds; methods for treating bacterial infections in a mammal using such compounds; and processes and intermediates useful for preparing such compounds.

Abstract: The present invention provides an improved process for the preparation of Cefixime of formula (I), a cephalosporine antibiotic with an improved quality in regard to color and solubility. This process includes: (i) reaction of 7-?-(4-chloro-2-alkoxycarbonyl methoxyimino-3-oxobutyromido)-3-cephem-4-carboxylic acid (V) with thiourea at pH 5.0 to 6.0 at temperature 25-40° C. in water, (ii) carbon treatment to the reaction mixture in presence of sodium dithionite or ethylenediaminetetraacetic acid (EDTA) followed by filtration, (iii) acidification of the filtrate obtained in step (ii) to pH 2.0 to 3.0 with acid at 50-80° C. to give cefixime ester (IV) (iv) alkaline hydrolysis of cefixime ester of formula (IV) in water followed by acidification to pH 5.0 to 6.0, (v) precipitation of cefixime (I) by adding ketone solvent followed by acidification to pH 2.0 to 3 and (vi) isolation of solid.

Abstract: The present invention provides Cephem compounds which have a wide antimicrobial spectrum and have potent antimicrobial activity against beta-lactamase producing Gram negative bacteria as follows: A compound of the formula: wherein, X is N, CH or C—Cl; T is S or the like; A and G are lower alkylene or the like; B is a single bond or the like; D is a single bond, —NR7—, —CO—, —CO—NR7—, —NR7—CO—, —NR7—CO—NR7—, or the like; E is optionally substituted lower alkylene; F is a single bond or optionally substituted phenylene; R3, R4, R5 and R6 each is independently hydrogen, halogene, nitrile, or the like; or an ester, a compound protected at the amino on the ring in the 7-side chain, a pharmaceutically acceptable salt, or a solvate thereof.

Abstract: A solid DMSO solvate of a compound of formula (I) is described, which is a useful intermediate for preparing the broad spectrum antibiotics Ceftobiprole and Ceftobiprole Medocaril.

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: A fluorescent probe which is represented by the following formula (I): (wherein, R1 represents a monovalent substituent other than hydrogen atom, carboxy group, or sulfo group; R2 represents hydrogen atom, or a monovalent substituent; R3 and R4 each independently represents hydrogen atom or a halogen atom; and R5 represents a monovalent group which is cleaved by contact with a measuring object, provided that a combination of R1 and R2 is selected so that the oxidation potential of the benzene ring to which they bind makes (1) the compound represented by the formula (I) substantially no fluorescent before the cleavage, and (2) a compound after the cleavage, which is derived from the compound represented by the formula (I), substantially highly fluorescent after the cleavage).

Abstract: This invention provides processes for preparing cefepime, including crystalline intermediates of Formula V.

Abstract: 7-[2-(2-aminothiazol-4-yl)-2-(methylcarbonyloxyimino)acetamido]-3-vinyl-cephem-4-carboxylic acid of formula (I), in the form of a crystalline salt and use thereof, e.g. in the preparation of pure cefdinir. In another aspect this invention relates to the compound of formula (I) in the form of a salt, optionally in crystalline form, wherein the salt is selected from the group consisting of phosphate, hydrogen phosphate, mesylate, tosylate, sulfate, hydrogen sulfate and sulfamate.

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: This invention provides cross-linked glycopeptide-cephalosporin compounds and pharmaceutically acceptable salts thereof which are useful as antibiotics. This invention also provides pharmaceutical compositions containing such compounds; methods for treating bacterial infections in a mammal using such compounds; and processes and intermediates useful for preparing such compounds.

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: 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: Crystalline acetonitrile solvate of cefuroxime acid, useful for preparing the antibiotic cefuroxime sodium salt.

Abstract: A process for the production of intermediates having a formula IA that can be used for the synthesis of cephalosporins, such as cefepime of formula V. The intermediates of formula IA are produced by desilyation of a compound of formula II wherein R4 is a silyl-protecting group, with a protic solvent to obtain a compound of formula III, and reacting the compound of formula III with an organic base of formula IV wherein R2 and R3 together represent a C4-alkylene group, and with the adjacent nitrogen atom form a saturated 5-membered heterocycle, and R1 represents a methyl group, to obtain the compound of formula 1A.

Abstract: A novel crystalline modification of cefuroximaxetil (?-modification), pharmaceutical compositions containing this modification, and their use.