Novel cephalosporins useful as antibacterial agents

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.

Novel compounds with high therapeutic index

The present invention is directed to novel therapeutic compounds comprised of an amino acid bonded to a medicament or drug having a hydroxy, amino, carboxy or acylating derivative thereon. These high therapeutic index derivatives have the same utility as the drug from which they are made, and they have enhanced pharmacological and pharmaceutical properties. In fact, the novel drug derivatives of the present invention enhance at least one therapeutic quality, as defined herein. The present invention is also directed to pharmaceutical compositions containing same.

METALLODRUGS HAVING IMPROVED PHARMACOLOGICAL PROPERTIES AND METHODS OF MANUFACTURE AND USE THEREOF

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. 1. An antimicrobial composition , comprising:a first moiety which is (i) an antimicrobial peptide (“AMP”), or peptide that binds to a pathogenic target, the sequence of which is between 6 and 100 amino acids, is net positively charged, and is amphipathic, (ii) an antibiotic, or (iii) a conjugate comprising an AMP, or peptide that binds to a pathogenic target, and an antibiotic; anda second moiety which is a metal binding moiety,wherein the first moiety and the second moiety are covalently linked to form a complex, andwherein the first moiety promotes uptake of the complex into a target cell or organelle.2. A composition according to claim 1 , wherein the first moiety comprises an antimicrobial peptide claim 1 , or peptide that binds to a pathogenic target claim 1 , that adopts a structure selected from the group consisting of an α-helix claim 1 , a β-hairpin-like beta-sheet claim 1 , a beta-sheet claim 1 , or an α-helix/beta-sheet mixed structure.3. A composition according to claim 2 , wherein the antimicrobial peptide claim 2 , or peptide that binds to a pathogenic target claim 2 , adopts an amphipathic α-helical structure.4. A composition according to claim 2 , wherein the antimicrobial peptide claim 2 , or peptide that binds to a pathogenic target claim 2 , adopts a structure comprising antiparallel β-sheets.5. A composition according to claim 2 , wherein the antimicrobial peptide claim 2 , or peptide that binds to a pathogenic target claim 2 , adopts an extended backbone ...

PROCESS FOR THE CRYSTALLISATION OF CEFADROXIL MONOHYDRATE

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. 1. Cefadroxil monohydrate in crystal form obtained by a process comprising: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; andc) isolating the cefadroxil monohydrate in crystal form from the suspension obtained in step b).2. Cefadroxil monohydrate according to claim 1 , wherein step a) and step b) are carried out at a temperature of between 5 and 25° C.3. Cefadroxil monohydrate according to claim 1 , wherein lowering the pH in step b) is carried out within a period of time of between 20 to 60 min.4. Cefadroxil monohydrate according to claim 1 , wherein the suspension of the cefadroxil monohydrate in crystal form obtained in step b) is stirred for 10 to 120 min.5. Cefadroxil monohydrate according to claim 1 , wherein the cefadroxil in crystal form is isolated from the suspension obtained in step b).6. Cefadroxil monohydrate in crystal form with a CIE b value of below 6.7. Cefadroxil monohydrate in crystal form with a CIE b value of below 12 when stored at a temperature of 25t for at least 1 month.8. A pharmaceutical composition comprising cefadroxil monohydrate as defined in claim 6 , and a pharmaceutically acceptable carrier. This application is a continuation of commonly owned co-pending U.S. patent application Ser. No. 12/300 ...

Regulation of nitric oxide release and biofilm development

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.

New crystal form of cefathiamidine compound and preparation method therefor

A novel crystalline form of Cefathiamidine compound and its preparation method, characterizing in its X-ray powder diffraction pattern and differential scanning calorimetry thermogram. Dissolving Cefathiamidine compound with a purity of 98% or higher in a solvent at a temperature of 30˜45° C. to form a solution, whose concentration is controlled within 0.05˜0.2 g/mL, and then adding a solventing-out agent to the solution, wherein the amount of the solventing-out agent is 3˜5 times (in volume) of that of the solvent; followed by cooling the solution down to 0˜10° C. at a rate of 0.2˜1° C./min; continuing to stir for 1˜3 hours, and separating the obtained solid-liquid suspension to provide a novel crystalline form of Cefathiamidine compound after drying.

Antibacterial compositions

Pharmaceutical compositions comprising cefepime or a pharmaceutically acceptable salt thereof, tazobactam or a pharmaceutically acceptable salt thereof, and arginine or a pharmaceutically acceptable salt thereof; and their use in treatment, control or prevention of bacterial infection is disclosed.

Broad Spectrum Beta-Lactamase Inhibitors

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. 119-. (canceled)20. A method of treating bacterial infection , the method comprising:administering to an individual in need of treatment a therapeutically effective amount of a beta-lactam antibiotic;wherein the beta-lactam antibiotic is also a beta-lactamase inhibitor that inhibits a beta-lactamase enzyme andwhich comprises a leaving group that is in conjugation with the lactam nitrogen of the beta-lactam ring through a styryl moiety such that, when the beta-lactam ring is opened by the beta-lactamase enzyme to form a ring-opened compound, the leaving group is expelled to form a reactive moiety on the ring-opened compound, and the reactive moiety covalently binds to the beta-lactamase enzyme, wherein the reactive moiety is a substituted or unsubstituted cyclohexadienyl methide.22. The method of claim 21 , wherein Rand Rare both hydrogen.23. The method of claim 21 , wherein Rand Rare independently selected from hydrogen claim 21 , halogen claim 21 , (C1-C6) alkyl claim 21 , and (C1-C6) alkoxy.26. The method of claim 25 , wherein Ris hydrogen.27. The method of claim 25 , wherein Rand Rare independently selected from hydrogen claim 25 , halogen claim 25 , (C1-C6) alkyl claim 25 , and (C1-C6) alkoxy.30. The method of claim 20 , wherein the beta-lactam antibiotic is a cephalosporin claim 20 , a carbapenem or a monobactam.31. The beta-lactam antibiotic of claim 20 , wherein the beta-lactam antibiotic is a ...

CEPHALOSPORIN COMPOSITIONS AND METHODS OF MANUFACTURE

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. 113-. (canceled)145. A composition comprising a compound of formula (V) , or a salt thereof , selected from the compounds of Table 2 , or salts thereof , prepared according to the method of claim .16. A method of treating a bacterial infection in a patient claim 15 , comprising the step of administering to the patient a composition of .2021-. (canceled) This application claims priority to U.S. Provisional Application No. 61/782,365, filed Mar. 14, 2013. The entire content of this application is incorporated herein by reference in its entirety.The present disclosure relates to cephalosporin compositions and the manufacture thereof.Cephalosporin compounds containing the chemical substructure of formula (I) are important antibacterial therapeutic agents. The manufacture of these cephalosporin compounds is typically performed in a series of synthetic chemical reactions. Reducing the number of synthetic chemical reactions and associated purification steps can increase product yield and decrease the time for production, thereby increasing efficiency and decreasing production costs.Syntheses of antibiotic cephalosporin compounds containing the substructure of formula (I) typically require two reactions for the formation of a 7-carboxamide moiety: (1) deprotection (i.e., removal of a protecting group) of the 7-amino group, and (2) acylation of the 7-amino group to form the 7-carboxamide moiety. One example of this two-step procedure is disclosed in U.S. Pat. No. 5,134,138 (see ). Most cephalosporin antibiotics can be manufactured in an analogous way. Ceftolozane (CXA-101, FR264205) is a cephalosporin antibiotic compound, a synthesis of which is disclosed in U.S. Pat. No. 7,129,232. Additional cephalosporin antibiotic compounds include the compounds of Table 2. There remains an unmet need to ...

Platform drug delivery system utilizing crystal engineering and theanine dissolution

A platform drug delivery system and a method of improving the delivery of low solubility pharmaceuticals utilizing crystal engineering and Theanine dissolution resulting in enhanced bioactivity, dissolution rate, and solid state stability.

INTERMEDIATES IN THE SYNTHESIS OF CEPHALOSPORIN COMPOUNDS

Described herein are crystalline forms of a compound of formula (III), including toluene solvates off A TD-CLE, as well as processes for the preparation thereof and use thereof in the preparation of cephalosporin compounds such as ceftolozane. Provided herein is a crystalline form of a compound of formula (III): wherein X is CI, Br, or I; and R1 and R2 are each independently an oxygen protecting group; processes for making the crystalline form, and use of said form in the synthesis of antibacterial cephalosporins such as ceftolozane. 2. The crystalline form of claim 1 , wherein Rand Rare each independently tert-butyldimethylsilyl claim 1 , tert-butyl claim 1 , 4-methoxybenzyl claim 1 , 2-methoxybenzyl claim 1 , or triphenylmethyl.4. The crystalline form of which is a solvate of an aromatic solvent.5. The crystalline form of claim 4 , wherein the aromatic solvent is toluene claim 4 , xylene claim 4 , ethylbenzene claim 4 , benzene claim 4 , cumene claim 4 , or mixtures thereof.6. The crystalline form of claim 5 , which is a toluene solvate.7. The crystalline form of claim 4 , which is in about 1:1 molar ratio of compound (III) to solvent.8. The crystalline form of claim 1 , wherein the form has an X-ray powder diffraction pattern comprising one or more characteristic peaks expressed in degrees 2θ at about 6.1 claim 1 , about 12.1 claim 1 , about 13.1 claim 1 , about 18.5 claim 1 , and about 24.3.9. The crystalline form of claim 1 , wherein the form has an X-ray powder diffraction pattern comprising one or more characteristic peaks expressed in degrees 2θ at about 7.3 claim 1 , about 10.0 claim 1 , about 11.6 claim 1 , about 17.7 claim 1 , and about 24.6.11. The process of claim 10 , wherein Rand Rare each independently tert-butyldimethylsilyl claim 10 , tert-butyl claim 10 , 4-methoxybenzyl claim 10 , 2-methoxybenzyl claim 10 , or triphenylmethyl.13. The process of claim 10 , wherein the aromatic solvent comprises toluene.14. The process of claim 13 , wherein the ...

Intermediates in the synthesis of cephalosporin compounds

Described herein are crystalline forms of a compound of formula (III′), including toluene solvates of TATD-CLE, as well as processes for the preparation thereof and use thereof in the preparation of cephalosporin compounds such as ceftolozane.

Broad Spectrum Beta-Lactamase Inhibitors

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. 3. The compound or pharmaceutically acceptable salt of claim 2 , wherein each Ris independently selected from hydrogen or halogen and each Ris independently selected from hydrogen claim 2 , halogen or —CH—X and at least one Ris —CH—X.4. The compound or pharmaceutically acceptable salt of claim 2 , wherein each Ris hydrogen and each Ris independently selected from hydrogen or —CH—X and at least one Ris —CH—X.8. The compound or pharmaceutically acceptable salt of claim 7 , wherein each Ris independently selected from hydrogen or halogen and each Ris independently selected from hydrogen claim 7 , halogen or —CH—X and at least one Ris —CH—X.9. The compound or pharmaceutically acceptable salt of claim 7 , wherein each Ris hydrogen and each Ris independently selected from hydrogen or —CH—X and at least one Ris —CH—X.16. The compound or pharmaceutically acceptable salt of claim 15 , wherein each Ris independently selected from hydrogen or halogen and each Ris independently selected from hydrogen claim 15 , halogen or —CH—X and at least one Ris —CH—X.17. The compound or pharmaceutically acceptable salt of claim 15 , wherein each Ris hydrogen and each Ris independently selected from hydrogen or —CH—X and at least one Ris —CH—X. This application is a continuation of U.S. application Ser. No. 15/808,204, filed Nov. 9, 2017, which is a continuation of U.S. application Ser. No. 15/247,536, filed Aug. 25, 2016, which is a ...

Derivatized 3-Styryl-Cephalosporins

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. 2. The compound of wherein Z is —S— and Ris H.3. The compound of wherein Z is —S— and Ris —OCH.4. The compound of wherein Z is —CH— or —O—.5. The compound of wherein L is —CH—.613.-. (canceled)14. The compound of wherein Ris hydrogen.1516.-. (canceled)17. The compound of wherein R claim 1 , Rand Rare all hydrogen.18. The compound of wherein R claim 1 , R claim 1 , Rand Rare all hydrogens.1922.-. (canceled)2313. The compound of any one of - wherein R claims 1 , R claims 1 , RRand Rare all hydrogens.29a. (canceled)3336.-. (canceled)37. The compound of wherein R claim 32 , Rand Rare all hydrogen.38. The compound of wherein R claim 32 , R claim 32 , Rand Rare all hydrogens.39. The compound of wherein:{'sup': 5', '7', '8', '6, 'R, Rand Rare all hydrogen and Ris nitro.'}44. The compound of wherein X is a halide.45. The compound of wherein X is chloride.50. The compound of wherein all Rare hydrogen.51. The compound of wherein Ris hydrogen claim 49 , Ris hydrogen claim 49 , methyl claim 49 , ethyl claim 49 , —CH—COH claim 49 , —CH—CH—COOH claim 49 , or —C(CH)—COOH and Ris hydroxyl.55. (canceled)56. A pharmaceutical composition comprising a therapeutically effective amount of one or more compounds of .57. A method of treatment of infections claim 1 , which comprises the step of administering a therapeutically effective amount of one or more compounds of to an individual in need of treatment.58. A method of inhibiting ...

Broad Spectrum Beta-Lactamase Inhibitors

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.

BROAD SPECTRUM BETA-LACTAMASE INHIBITORS

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. 5. The compound or pharmaceutically acceptable salt of claim 2 , wherein Rand Rare hydrogen.7. The compound or pharmacologically acceptable salt thereof of claim 6 , wherein X is halogen claim 6 , pyridinium claim 6 , phenoxy claim 6 , pentafluorophenoxy claim 6 , or tosyl.8. The compound or pharmacologically acceptable salt thereof of claim 6 , wherein X is halogen or pyridinium.9. The compound or pharmacologically acceptable salt thereof of claim 6 , wherein X is halogen or pyridinium and each Ris independently hydrogen claim 6 , an optionally substituted C1-C6 alkyl or an optionally substituted C6-C12 aryl.10. The compound or pharmaceutically acceptable salt thereof of claim 6 , wherein each Ris hydrogen.12. The compound or pharmacologically acceptable salt thereof of claim 11 , wherein X is halogen claim 11 , pyridinium claim 11 , phenoxy claim 11 , pentafluorophenoxy claim 11 , or tosyl.13. The compound or pharmacologically acceptable salt thereof of claim 11 , wherein X is a halogen or pyridinium.14. The compound or pharmacologically acceptable salt thereof of claim 13 , wherein X is Cl or Br.16. A pharmaceutical composition comprising a therapeutically effective amount of one or more compounds of .17. A pharmaceutical composition comprising a therapeutically effective amount of one or more compounds of .18. A method of treatment of a bacterial infection which comprises the step of administering a ...

SYNTHESIS PROCESS OF PRECURSORS OF DERIVATIVES OF BETA-LACTAM NUCLEI AND PRECURSORS AND DERIVATIVES THEREOF

A synthesis process of precursors of derivatives of beta-lactam compounds, said beta-lactam compounds being selected from 6-aminopenicillanic acid and 7-aminocephalosporanic acid, preferably 6-aminopenicillanic acid, comprising the following steps: a) protection of the amine group of the beta-lactam compound, selected from 6-aminopenicillanic acid and 7-aminocephalosporanic acid, preferably 6-aminopenicillanic acid, through the formation of a carbamate by reaction with a dicarbonate; b) esterification of the carboxyl group in position 2 of the beta-lactam compound obtained in step a) by reaction with propargyl alcohol. 1. A synthesis process of precursors of derivatives of β-lactam compounds , said β-lactam compounds being selected from 6-aminopenicillanic acid and 7-aminocephalosporanic acid , comprising the following steps:a) protection of the amine group of the β-lactam compound, selected from 6-aminopenicillanic acid and 7-aminocephalosporanic acid through the formation of a carbamate by reaction with a dicarbonate;b) esterification of the carboxyl group in position 2 of the β-lactam compound obtained in step a) by reaction with propargyl alcohol.2. A synthesis process of triazole derivatives of β-lactam compounds wherein the precursor obtained according to is subjected to a further step c):c) cycloaddition reaction between the precursor obtained in step b) and an organic azide, with the formation of the corresponding triazole derivative of the β-lactam compound.3. The process according to wherein step a) is carried out by reaction with an alkyl claim 1 , aromatic or cyclic dicarbonate.4. The process according to claim 1 , wherein step a) is carried out at room temperature for a time ranging from 10 to 32 hours claim 1 , in a solvent which is a mixture 1:1 by volume of 1 claim 1 ,4-dioxane and water or a mixture 1:1 by volume of tetrahydrofuran (THF) and water claim 1 , the di-(tent-butyl dicarbonate) being present in a molar ratio ranging from 2 to 1 with ...

Novel compounds

Complexo e processo para preparação de um composto

头孢菌素衍生物的制备方法

式(I)β-内酰胺或其盐抗菌素： 其中R 1 为氢，甲氧基或甲酰氨基； R 2 为酰基； CO 2 R 3 为羧基或羧酸根阴离子，或R 3 为易被消去的 羧基保护基；R 4 代表至多4个取代基；X为S，SO， SO 2 ，O或CH 2 ；m为1或2；n为0，用于治疗人体和 动物的细菌感染。

头孢菌素衍生物的制备方法

式(Ⅰ)β-内酰胺或其盐抗菌素： 其中R 1 为氢，甲氧基或甲酰氨基； R 2 为酰基； CO 2 R 3 为羧基或羧酸根阴离子，或R 2 为易被消去的羧基保护基；R 4 代表至多4个取代基；X为S，SO，SO 2 ，O或CH 2 ；m为1或2；n为0，用于治疗人体和动物的细菌感染。

Sulfide derivatives

FIELD: antibiotics. SUBSTANCE: product of the formula QR 2 SR 1 Het where Q - AcS, Hal; Ac - C 1 -C 12 -acyl, Het - 1,2,3-triazole-4-yl, R 1 - bond or C 1 -C 4 -alkylene, R 2 - C 1 -C 4 -alkylene. Product is used for cephalosporin synthesis. EFFECT: improved method of synthesis. 7 cl с66090с ПЧ Го ВОИ ”” 2 060 993 Сл 50° С 070 249/04 РОССИЙСКОЕ АГЕНТСТВО ПО ПАТЕНТАМ И ТОВАРНЫМ ЗНАКАМ 12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ РОССИЙСКОЙ ФЕДЕРАЦИИ (21), (22) Заявка: 93051089/04, 10.11.1993 (71) Заявитель: Сионоги Энд Ко., Лтд. (Р) (30) Приоритет: 19.07.1990 УР 191889/90 25.10.1990 УР 2897721/90 (72) Изобретатель: Тадатоси Кубота[Р], 21.11.1990 УР 319578/90 Масахару Куме[/Р] 19.06.1991 УР 147357/91 (73) Патентообладатель: ата публикации: 27.05. ионоги Энд Ко., Лтд. (46) Д 6 27.05.1996 С Энд Ко., Лтд. (УР) и (56) Ссылки: Франция, 2505840, С 070501/22, 1982. о (62) Первичная заявка, из которой выделена настоящая: 5001259/04 ©& © (54) ПРОИЗВОДНЫЕ СУЛЬФИДОВ < (57) Реферат: С 12-ацил, НеЁ - 1, 2, З-триазол-4-ил, Ка - Использование: В синтезе связь или Са - Сил-алкилен, В? - С. - > цефалоспоринов. Сущность: продукт - ‹о ОК2 ЗКа Не, где @ - Ас$, Нар Ас - С: - С д-алкилен. 6 з. п. ф-лы. © Сс' — 0 с66090с ПЧ Го КУЗЗАМ АСЕМСУ ГОК РАТЕМТ$ АМО ТКАОЕМАКК$ 12) АВЗТКАСТ ОЕ 1МУЕМТОМ (19) ВИ "” 2 060 993 ' (51) п. С1.6 [в 07 О 249/04 13) СЛ (21), (22) АррИсаНоп: 93051089/04, 10.11.1993 (30) РНошу: 19.07.1990 УР 191889/90 25.10.1990 УР 289772/90 21.11.1990 УР 319578/90 19.06.1991 /Р 147357/91 (46) Рае ог ричбИсаНоп: 27.05.1996 (62) Еа\ег аррйсаНоп: 5001259/04 (71) АррИсапе: Зюопод! Еппа Ко., Ца. (Р) (72) пуетог. — Таааюз Кираа[Р], МазаКкКпаги Ките]рР] (73) Ргорпеюг: Зопоа! Еппа Ко., Ша. (}Р) (54) ЗУЕЕОЕ ОЕКМАТМЕЗ$З (57) АБзГасЕ: НЕГО: апйбюйс$. ЗУВЗТАМСЕ: ргодис{ о Фе Югтуа ОВК Не мпеге @ - Ас$, На! Ас - С1-С12-асу|, Не - 1,2,3Пахое-4-У, Кл - ропа ог С1-Сл-акКуепе, К - С1-С.-аКуепе. Рго4дисЕ 1$ изеа ог серпаозропйп зупез$. ЕРЕЕСТ: итргоуеяа птеПоа оЁ зупПе$5. 7 с! 2060993 С1 КО с66090с% ПЧ] ГЭ ...

一种头孢唑肟钠化合物晶型、制备方法及其药物制剂

本发明公开了一种头孢唑肟钠化合物晶型，采用X-射线粉末衍射测定，其图谱中以衍射角2θ±0.2°表示的主要特征峰如下：4.7°，6.3°，6.7°，8.8°，9.4°，9.7°，12.1°12.5°，13.7°，14.1°，14.6°，16.4°，17.0°，17.7°，18.0°，18.5°，18.9°，19.8°，20.1°，21.2°。本发明还公开了上述晶型的制备方法及药物制剂。本发明通过对头孢唑肟钠的深入研究，发现经重结晶后得到了新的头孢唑肟钠晶型，该化合物晶型明显呈细小颗粒状，粒径分布均匀，流动性好，吸湿性减弱，其在生产过程中，无需粉碎，无静电，提高了产品装量的稳定性。

一种头孢氨苄共晶化合物及其制备方法

本发明公开了一种头孢氨苄共晶化合物，所述共晶化合物由一个头孢氨苄分子、一个2,6‑二羟基苯甲酸分子和一个水分子通过分子间作用力形成基本结构单元，再以基本结构单元重复排列形成。本发明将头孢氨苄和2,6‑二羟基苯甲酸制备得到头孢氨苄盐，该头孢氨苄盐为单晶体结构，该单晶结构呈均一稳定的固态形式，不仅能够保持头孢氨苄原有药物活性不改变，而且还有效改善了头孢氨苄在水中的溶解性，有助于其在体内的吸收，从而提高其药效的发挥。

Способы получения промежуточных соединений для 2-алкилцефемовых соединений

1. Способ получения соединения формулы (II) или его соли,[Химическая формула 1]где,Rпредставляет собой низший алкил;Y представляет собой уходящую группу;L представляет собой простую связь, низший алкилен или низший алкенилен;Pпредставляет собой ацил или амино-защитную группу;Pпредставляет собой карбокси-защитную группу;который включает:окисление соединения формулы (I) или его соли,[Химическая формула 2]где каждый символ имеет значение, определенное выше,с получением соединения формулы (II) или его соли.2. Способ получения соединения формулы (II) или его соли,[Химическая формула 3]гдеRпредставляет собой низший алкил;Y представляет собой уходящую группу;L представляет собой простую связь, низший алкилен или низший алкенилен;Pпредставляет собой ацил или амино-защитную группу;Pпредставляет собой карбокси-защитную группу;который включает:взаимодействие соединения формулы (IV) или его соли,[Химическая формула 4]гдеволнистая линия означает, что связь представляет собой смесь α-конфигурации и β-конфигурации;другие символы имеют значения, определенные выше,с основанием с получением соединения формулы (II) или его соли.3. Способ получения соединения формулы (II) или его соли,[Химическая формула 5]гдеRпредставляет собой низший алкил;Y представляет собой уходящую группу;L представляет собой простую связь, низший алкилен или низший алкенилен;Pпредставляет собой ацил или амино-защитную группу;Pпредставляет собой карбокси-защитную группу;который включает:окисление соединения формулы (I) или его соли,[Химическая формула 6]где каждый символ имеет значение, определенное выше,с получением соединения формулы (V) или его соли,[Химическая формула 7]где каждый символ имеет значение, РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) (51) МПК C07D 501/14 (13) 2015 120 084 A (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ (12) ЗАЯВКА НА ИЗОБРЕТЕНИЕ (21)(22) Заявка: 2015120084, 29.10.2013 (71) Заявитель(и): СИОНОГИ ЭНД КО., ЛТД. (JP) Приоритет(ы): (30) Конвенционный приоритет: 29.10.2012 US 61 ...

一种头孢克肟的精制方法

本发明公开一种头孢克肟的精制方法，属于医药技术领域。该方法包括：在一定初始浓度的头孢克肟盐有机溶剂与水的混合溶液中或水溶液中，在10～40℃温度下，加入酸，将溶液pH调节到3.25～3.75，同时搅拌，加入一定量晶种，并用在线pH计监控体系pH，5～30min后体系pH开始上升，此时缓慢加酸至终点pH＝2.20，降温养晶2～4小时；将产物过滤、洗涤、干燥后得到头孢克肟晶体。在未自发成核之前加入晶种，可以提高产物的结晶度，得到的产物稳定性好、白度高、粒度分布窄、流动性好、堆密度较大、含量高、产率高、水分与溶残达标。实验的重复性强，受外界因素干扰小，尤其适用于工业生产。

一种头孢地尼微粉的制备方法

本发明涉及一种头孢地尼微粉的制备方法，所述方法，步骤如下：将头孢地尼磷酸盐加入冷水中，用碱液调pH值为6.8-7.1，加入活性炭、保险粉、EDTA，搅拌，过滤，洗涤；滤液和洗涤液混合，搅拌下加入乙醇，乙醇加入量为冷水重量的1/10，用酸调pH值为4.1，养晶15-25分钟，继续酸调pH值为2.5-2.7，搅拌养晶0.5-2h，降温至15-25℃，搅拌养晶0.5-2h，降温至0-5℃，搅拌养晶0.5-2h。过滤，干燥，即得。

药物组合物的制备方法

一种药物组合物的制备方法,包括将式(Ia)化合物或其药学上可接受的盐或其在体内可水解的酯和药学上可接受的载体混合,所说式(Ia)为:其中R 1 、R 2 、R 3 、R 4 、X、m和m的定义详述于说明书中。

Synthesis method of ceftizoxime acid

本发明公开了一种头孢唑肟酸的合成方法，属于医药合成技术领域。本发明采用7‑ANCA与AE活性酯反应制备头孢唑肟酸。本发明合成方法简单，反应容易操作，收率及纯度较高，产品副产物少的优点，适合工业化生产。

Derivatives of thioalkylthiocephalosporin or their pharmaceutically acceptable salts, antibacterial composition

FIELD: organic chemistry, antibiotics. SUBSTANCE: product: derivatives of thioalkylthiocephalosporin of the formula where acyl - lower halogenalkylthio(lower)alkanoyl or group of the formula where R 3 - H, OH, imino, or group of the formula where: R 4 - H, protective group; R 5 - H, lower alkylene, oxygen, NOR 6 ; R 6 - H, protective group, lower alkyl, lower alkenyl, lower cycloalkyl, carboxy(lower)alkyl or carboxy(lower)alkenyl; Het - pyridyl, thiadiazolyl, triazolyl or tetrazolyl; R 1 - simple bond or methylene; R 2 - - methylene; X - S; Y - H. Synthesized compounds were used in medicine. EFFECT: improved method of synthesis. 3 cl (19) 13) ВИ “” 2071 963 Сл 51) М с 070 501/06, 501/59, А 671 К 31/545 РОССИЙСКОЕ АГЕНТСТВО ПО ПАТЕНТАМ И ТОВАРНЫМ ЗНАКАМ 12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ РОССИЙСКОЙ ФЕДЕРАЦИИ (21), (22) Заявка: 5001259/04, 18.07.1991 (71) Заявитель: Сионоги энд Ко., Лтд. (ЦР) (30) Приоритет: 19.07.1990 УР 191889/90 25.10.1990 УР 289772/90 21.11.1990 УР 319578/90 19.06.1991 УР 147357191 (72) Изобретатель: Тадатоси Кубота[Р], Масахару Куме]Р] (73) Патентообладатель: соон с 96 0с ПЧ Го алкилен, кислород, МОВб; Кб-Н, защитная (46) Дата публикации: 20.01.1997 Сионоги энд Ко., Лтд. (Р) < (56) Ссылки: Патент США М 4604367, кл. А 61 К о 31/545 1986. Заявка Японии М 62-99380, кл. А 61 К 31/545, 1985. Машкосвский М.Д. Средства.- М., Медицина, 1988, ч. 2, с. 216 © - 218. <о (54) ПРОИЗВОДНЫЕ ТИОАЛКИЛТИОЦЕФАЛОСПОРИНА ИЛИ ИХ ФАРМАЦЕВТИЧЕСКИ ПРИЕМЛЕМЫЕ © СОЛИ, АНТИБАКТЕРИАЛЬНАЯ КОМПОЗИЦИЯ = (57) Реферат: 7х (11), ^ Использование: в медицине. Сущность фене изобретения: продукт: производные — | З © тиоалкилтиоцефалоспорина ф-лы . Е с: где К?-Н, ОН, имино, или группа ф-лы Ацил-нн и К ь СТТТ» ‚, т у ИБ в . ДУ! г] ^в^” “’-неф, где с1> в мн 5 > 57 где Р“-Н, защитная группа, В ?-Н, низший О где ацил низший галогеналкилтио(низший)алканоил или группа (11) группа, низший алкил, низший алкенил, низший циклоалкил, карбокси(низший)алкил или карбокси(низший)алкенил; Не - пиридил, ...

Process for preparing 3'-substituted-5'-(2-amino-4-pyridyl)-1',2'4'-triazoles

3-(2-alkylamino-4-pyridinyl)-1,2,4-triazole derivs. (I), used as antagonists of histamine H2 receptors and antiulcer agents, are new (where R1 = H, Me or Et; Y = H, CH2 OH, alkyl or (CH2)nNHC(Z) -Q; n = 1 - 4; Z + Q form a 4-pyrimidinone gp. (sic.); or Z = 0, S, N-CN or CH-NO2; and Q = CH:CHR2 or (CH2)mR3; R2 = 2-methyl-5thiazolyl, 4- pyridinyl or 4-imidazolyl; R3 = H, alkyl, thioalkoxy, alkoxy, NH2, mono- or di-alkylamino, 2-guanidino-4-thiazolyl, 5-methyl-4- imidazolyl or Ph, 3- or 4-pyridinyl, all 3 gps. being opt. mono- substd. by halogen, alkoxy, OH or alkylamino; and m = 0 - 3).

Bicyclic beta-lactame/parabene complexes

Amino acyl cephalosporin derivatives

Antibacterial cephalosporin compounds of the Formula (I): ##STR1## wherein W is a pharmaceutically acceptable salt or a carboxyl-protecting group; n is an integer from 1 to 2; --X-- is --X 1 -- where the X 1 moieties are the same or different and selected from the group consisting of (D) or (L) ##STR2## Y is --O--; wherein R 1 is selected from the group consisting of: ##STR3## R 2 is H, --CH 2 R 4 , --CHR 5 2 or --CR 5 3 , wherein R 4 is H, F, Cl, Br, --OH, --CN, ##STR4## --CH(CH 3 ) 2 , --CH 2 (OH), ##STR5## or --C.tbd.CH, where Q 1 , Q 2 and Q 3 are the same or different and selected from the group consisting of H, F, Cl or Br; R 5 is F, Cl or Br; and Z 1 is H or an amino protecting group.

Cephalosporin compounds, and antibacterial agents

A cephalosporin compound having the formula: ##STR1## wherein R 1 is a hydrogen atom, a halogen atom, a methoxy group, a substituted or unsubstituted vinyl group, or --CH 2 --A wherein A is a hydrogen atom, an azido group, an acyloxy group, a carbamoyloxy group, a subsituted or unsubstituted heterocyclic group (wherein the hetrocyclic ring is a 5- or 6-membered heterocyclic ring having from 1 to 4 oxygen, nitrogen or sulfur atoms), or a substituted or unsubstituted heterocyclic thio group (wherein the heterocyclic ring is a monocyclic or bicyclic heterocyclic ring having from 1 to 5 oxygen, nitrogen or sulfur atoms), or a pharmaceutically acceptable salt thereof.

Cephalosporin derivatives useful as .beta.-lactamase inhibitors and compositions and methods of use thereof

The present invention relates to cephalosporin derivatives having ß- lactamase inhibitory activity. The compounds are useful in preventing or treating bacterial resistance to an antibiotic, e.g. a ß-lactam antibiotic. Disclosed herein are compounds that are inhibitors of class B metallo-ß-lactamases, as well as class A, C, and D serine ß-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.

Cefradine compound prepared by adopting high-flux medicine crystal form rapid screening technology and preparation thereof

本发明公开了一种采用高通量药物晶型快速筛选技术制备的头孢拉定化合物。“高端医药产品精制结晶技术的研发与产业化项目”获得2015年国家科学技术进步二等奖，高通量药物晶型快速筛选技术属于高端医药产品精制结晶技术中的一项。所述头孢拉定化合物采用X‑射线粉末衍射测定，其图谱中以衍射角2θ表示的主要特征峰为11.46±0.2°，18.47±0.2°，20.85±0.2°，23.21±0.2°，29.32±0.2°。该化合物纯度高、杂质含量低、流动性好、稳定性好。同时，本发明还公开了一种采用上述头孢拉定制备的制剂即注射用头孢拉定。该制剂制备过程简单，不需任何赋形剂，较以往制剂具有更好的溶解性和稳定性且副作用小。

Process for preparing 3-iodomethyl cephalosporins

(Alkanoyloxymethyl)- and (carbamoyloxy methyl) cephems were treated with trialkylsilyl iodides to yield iodomethyl analogs [II; R=H, CH2CN, halomethyl, phenoxyalkyl, phenylthio-alkyl, phenylalkyl, thienyl-, furyl-, benzothienyl, (un)substituted 5-oxazolymethyl, 5-thiazolylmethyl, 5-imidazolylmethyl etc.; Ro=H, OMe; R1=alkyl, CH2CCl3, Ch2I, CHPh2, (un) substituted benzyl, Na, K, trialkylsilyl. 4-Nitrobenzyl 7-phenoxyacetamido-3-acetoxymethyl-3-cephem-4-carboxylate in CH2Cl2 was treated with Me3SiI to give II (R=PhOCH2; Ro=H;R1=4-O2NC6H4CH2).

Method for determining cefotaxime by reversed-phase high-performance liquid chromatography

FIELD: technological processes.SUBSTANCE: present invention relates to a method of determining cefotaxime by reversed-phase high-performance liquid chromatography, comprising an isocratic mode of elution using a chromatographic column filled with a sorbent with particle size of 5 mcm, used as a mobile phase is a mixture of a solution of ammonium acetate with acetonitrile, characterized by the fact that chromatographic separation is carried out on a column with size of 250×3 mm, filled with sorbent C18, using as a mobile phase mixture of 0.02 M ammonium acetate solution pH = 4.7 with acetonitrile in ratio of 90:10 using ultraviolet detector at wave length 252 nm and volume of introduced sample 10 mcl.EFFECT: effective separation of cefotaxime with impurity compounds of the sample and providing high retention of cefotaxime, which increases sensitivity and resolution of the method, reduced consumption of the mobile phase, which increases cost-effectiveness of analysis.1 cl, 2 dwg, 1 ex РОССИЙСКАЯ ФЕДЕРАЦИЯ (19) RU (11) (13) 2 687 493 C1 (51) МПК G01N 30/02 (2006.01) G01N 30/10 (2006.01) G01N 30/26 (2006.01) G01N 30/50 (2006.01) G01N 30/74 (2006.01) C07D 501/06 (2006.01) ФЕДЕРАЛЬНАЯ СЛУЖБА ПО ИНТЕЛЛЕКТУАЛЬНОЙ СОБСТВЕННОСТИ C07D 501/24 (2006.01) C07D 417/12 (2006.01) (12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ (52) СПК G01N 30/02 (2019.02); G01N 30/10 (2019.02); G01N 30/26 (2019.02); G01N 30/50 (2019.02); G01N 30/74 (2019.02); C07D 501/06 (2019.02); C07D 501/24 (2019.02); C07D 417/12 (2019.02) (21) (22) Заявка: 2018135531, 08.10.2018 08.10.2018 Дата регистрации: Приоритет(ы): (22) Дата подачи заявки: 08.10.2018 (45) Опубликовано: 14.05.2019 Бюл. № 14 C 1 (73) Патентообладатель(и): Федеральное казённое учреждение здравоохранения "Ставропольский научно-исследовательский противочумный институт" Федеральной службы по надзору в сфере защиты прав потребителей и благополучия человека (RU) (56) Список документов, цитированных в отчете о поиске: N. Lalitha, P.S. Pai: "Development R U 2 6 ...

Crystalline form of 7beta((z)-2-(2-aminothiazol-4-yl)-4- carboxybut-2-enoylamino)-3-cephem-4-carboxylic acid and pharmaceutical compositions

Vinyl cephalosporin compound that replaces and preparation method thereof and as the application of medicine

如下式所示的β-内酰胺化合物及其盐，式中R 1 、R 2 、R 3 和R 4 各自代表氢或一种不同的有机基团，R 5 为卤素，CN，CF 3 ，COOH，烷氧羰基，烷基或芳基磺酰基，烷基或芳基磺酰氧基，任意取代的H 2 SO 2 -；或任意取代的环烷基，环烷基烷基，炔烃基，芳基或杂环基。

Preparation process of cefathiamidine

本发明属于医药技术领域，公开了一种头孢硫脒的制备工艺。以7‑ACA为原料，经硅烷化，与氯乙酰氯反应生成氯乙酰7‑ACA，在催化剂的作用下，与N,N‑二异丙基硫脲反应，生成头孢硫脒，与现有技术相比，本发明提供的头孢硫脒的制备工艺简单，产品杂质含量少，纯度较高，适合工业化生产。

Method of isolation of cefaclor from a reaction mixture of an enzymatic acylation

FIELD: biochemistry. SUBSTANCE: method involves addition of anthraquinone-1,5-disulfoacid or its salt in combination with alkaline metal to a reaction mixture of an enzymatic acylation followed by if necessary acidification with hydrochloric acid to isolate cefaclor/anthraquinone salt-1,5- -disulfoacid at ratio 1:2. EFFECT: improved effectiveness of isolation, decreased cost of a procedure. 9 cl, 1 tbl, 3 ex ЕРУЭСТЬС ПЧ Го (19) РОССИЙСКОЕ АГЕНТСТВО ПО ПАТЕНТАМ И ТОВАРНЫМ ЗНАКАМ ВИ” 2 126 411 Сл 57 М ° С 070 501/12 (21), (22) Заявка: 95118294/04, 01.02.1994 (30) Приоритет: 05.02.1993 Ш$ 08014,015 (46) Дата публикации: 20.02.1999 (56) Ссылки: ЗИ 468430 А, 10.11.75. 4$ 3676434 А, 11.07.72. 4$ 3816233 А, 11.07.74. ЕР 0341991 А, 15.12.89. (85) Дата перевода заявки РСТ на национальную фазу: 05.09.95 (86) Заявка РСТ: 4$ 94/01375 (87) Публикация РСТ: М/О 94/18209 (18.08.94) (98) Адрес для переписки: 103735 Москва, ул.Ильинка 5/12 СОЮЗПАТЕНТ Лебедевой Н.П. (71) Заявитель: Эли Лилли энд Компани (1$) (72) Изобретатель: Джон Пол Гарднер (ЦЗ) (73) Патентообладатель: Эли Лилли энд Компани (0$) (57) Реферат: Изобретение относится к способу выделения цефаклора из реакционной смеси ферментативного ацилирования путем добавления антрахинон-1 ‚5-дисульфокислоты или ее соли с щелочным металлом к названной смеси с последующим при (54) СПОСОБ ВЫДЕЛЕНИЯ ЦЕФАКЛОРА ИЗ РЕАКЦИОННОЙ СМЕСИ ФЕРМЕНТАТИВНОГО АЦИЛИРОВАНИЯ необходимости подкислением соляной кислотой для выделения соли цефаклор/ антрахинон-1,5-дисульфокислоты в соотношении 1:2. Данное изобретение обеспечивает эффективный и требующий меньших затрат времени способ выделения. 1 с. иЗз.п. ф-лы, 1 табл. 12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ РОССИЙСКОЙ ФЕДЕРАЦИИ 2126411 С1 КО ЕРУЭСТЬС ПЧ Го КУЗЗАМ АСЕМСУ ГОК РАТЕМТ$ АМО ТКАОЕМАКК$ (19) 12) АВЗТКАСТ ОЕ 1МУЕМТОМ ВИ "” 2 126 411 ' (51) 1пЕ. С1.6 13) Сл С 070 501/12 (21), (22) АррИсаНоп: 95118294/04, 01.02.1994 (30) Рпошу: 05.02.1993 Ц$ 08/014,015 (46) Рае ог рибИсаНоп: 20.02.1999 (85) Соттепсетеп ...

Noval chemical compound and preparation method and purposes containing cephalosporin structure

本发明公开了含有头孢菌素结构的新化合物以及该化合物的制备方法和用途。该含有头孢菌素结构的新化合物制备成的药物比其他形式的药物或药剂在治疗眼内炎疾病的效果更好。

Cephalosporin compounds, their pharmaceutically acceptable nontoxic salts, physiologically hydrolyzable esters, isomers having e-configuration of double bond in propenyl group, syn-isomers and optical isomers and a method of their synthesis

FIELD: organic chemistry, antibiotics. SUBSTANCE: product: cephalosporin of the general formula (I): , its pharmaceutically acceptable nontoxic salt, physiologically hydrolyzable ester, hydrate or solvate or its isomers where Q means CH or N; R 1 means hydrogen or amino-protective group; R 2 and R 3 can be similar or different and mean independently hydrogen or hydroxy-protective group; or R 2 and R 3 together can form cyclic diol-protective group; R 4 means hydrogen or carboxyl-protective group; R 5 ,R 6 and R 7 independently mean hydrogen, amino or substituted amino, hydroxy, alkoxy, C 1-4 -alkyl, carboxyl or alkoxycarbonyl, or R 5 and R 6 together with carbon atoms to which they bound can form C 3 -C 7 -cycle. EFFECT: improved method of synthesis. 4 cl, 2 tbl Ос7Ууз60с ПЧ Го (19) РОССИЙСКОЕ АГЕНТСТВО ПО ПАТЕНТАМ И ТОВАРНЫМ ЗНАКАМ (51) МПК 13) ВИ” 2 098 420 ^^ Сл 31/545, С 07 М 7:00, 9:00 С 070 501/24, 501/04/А 61 К 12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ РОССИЙСКОЙ ФЕДЕРАЦИИ (21), (22) Заявка: 94032285/04, 09.09.1994 (30) Приоритет: 11.09.1993 КК 93-18321 (46) Дата публикации: 10.12.1997 (56) Ссылки: 1. ЕР, патент, 264091, кл.С 070 501/24, 1988. 2. ЕР, патент, 315518, кл.С 070 501/24, 1989. 3. ЕР, патент, 329785, кл.С 070 501/24, 1989. 4. ЕР, патент, 462009, кл.С 070 501/24, 1991.5. ЕК, патент, 2663332, кл.) 070 501/24, 1991. 6. ЕК, патент, 2678273, кл.С 070 501/24, 1992. (71) Заявитель: Лаки Лтд. (КК) (72) Изобретатель: Джае Хонг Йео[КН], Чан Сик Бан[КК], Джонг Чан Лим[КК], Йунг Мин ВУКК], Деог Хо ЯнГКК], Се Хо Ким[КВ], Джае Хун Джеон[КН], Му Йонг Ким[КК], Сам Сик Ким[КК]|, Тае Хи Ли[КК], Йонг Цу Ким[КВ1, Хун Сеунг Ох[КК] (73) Патентообладатель: Лаки Лтд. (КК) (54) СОЕДИНЕНИЯ ЦЕФАЛОСПОРИНА, ИХ ФАРМАЦЕВТИЧЕСКИ ПРИЕМЛЕМЫЕ НЕТОКСИЧНЫЕ СОЛИ, ФИЗИОЛОГИЧЕСКИ ГИДРОЛИЗУЕМЫЕ СЛОЖНЫЕ ЭФИРЫ, ИЗОМЕРЫ, ИМЕЮЩИЕ Е-КОНФИГУРАЦИЮ ДВОЙНОЙ СВЯЗИ В ПРОПЕНИЛЬНОЙ ГРУППЕ, СИН-ИЗОМЕРЫ И ОПТИЧЕСКИЕ ИЗОМЕРЫ И СПОСОБ ИХ ПОЛУЧЕНИЯ (57) Реферат: Настоящее изобретение относится к соединению ...

Processes for production of intermediates for 2-alkyl cephem compounds

本发明涉及用于制备可用作抗微生物药物的2-烷基头孢烯化合物的中间体的生产方法。本发明提供了一种方法，其包括，氧化式(I)的化合物或其盐以得到式(II)的化合物或其盐，其中每个符号如在说明书中所定义。

Cefprozil compound, and dispersible tablets, dry suspension and preparation method thereof

本发明涉及医药领域，具体讲，涉及一种头孢丙烯化合物、其分散片、干混悬剂及制备方法。本发明的头孢丙烯化合物为晶体，使用Cu-Kα射线测量得到的X-射线粉末衍射图如图1所示。经实验检测，本发明的头孢丙烯分散片、干混悬剂稳定性优越，气味和口感很好，非常适合临床应用。

Process for preparing -lactam antibiotics

내용 없음.

Refining method of cefprozil

本发明涉及一种头孢丙烯的精制方法，包括头孢丙烯粗品的合成和头孢丙烯的精制，其中精制包括：1)将头孢丙烯粗品加入乙醇中，搅拌，用稀盐酸水溶液调节pH至2.0～2.2，搅拌，粗品溶解，过滤，得到头孢丙烯盐的粗品溶液；2)向上述溶液中滴加4％的碳酸氢钠溶液，调节pH至4.6～5.0，降温，保温搅拌，抽滤，洗涤，抽干，得固体；3)将步骤2)所得固体溶解于水中，加入活性炭，加热至30～35℃，充分搅拌，过滤后得滤液，将滤液冷却至0～5℃，加入到混合溶剂中，析晶，控制温度及搅拌速度养晶1.5h，过滤，洗涤，抽干，真空干燥，得头孢丙烯纯品。本发明提供的精制方法具有条件简单，顺式异构体含量高等优点。

Cephalosporin derivative

(57)【要約】本公報は電子出願前の出願データであるた め要約のデータは記録されません。

Refining method of ceftizoxime sodium

本发明公开了一种头孢唑肟钠的精制方法，精制步骤包括：头孢唑肟酸加入水溶解，溶清后加浓盐酸控制pH，加碳酸氢钠，加入有机溶剂，进行搅拌均匀，加活性炭进行脱色，过滤，将温度控制在15‑20℃，快速搅拌30‑40HZ，加丙酮，降温至0‑5℃，将搅拌速度控制在20HZ，进行养晶1‑2h，干燥，制得头孢唑肟钠精品。通过本发明的精制方法，所得的头孢唑肟钠纯度能够达到99.9％以上，总杂质和最大单个杂质分别控制在0.2％,0.05％以内，产品的质量得到了显著的提高，且精制过程操作简便，适合工业化生产。

β-lactam compound, method for producing the same and drug

Process for the preparation of 3'-bromo-substituted deacetoxycephalosporanic acid sulphoxide derivatives

The title compds. of formula (B) were prepd. by protecting the 4- carboxy gp. of a 3'-unsubstd. cephalosporanic acid sulfoxide by silylating the mixt. in an inert, anhydrous, organic solvent with a silylating agent contg. at least 1 N-bound silyl gp. (A). After neutralizing any base generated or left behind by the silyl donor, the silylated compd. was brominated in situ. The silylating agent is pref., e.g. hexamethyl disilazane, N,N'-bis(trimethylsilyl) urea, 1,3-bis(trimethylsilyl) hydrotoin, etc. Bromination is pref. effected using N-bromosuccinamide, N-bromocaprolactam, Nbromoacetamide, etc. Neutralizing acids are pref. methanesulfonic acid, formic acid, etc. R1 is acylamino; R',R" and R"' are independently C1-6 alkyl or aryl.

Method of producing cephalosporane derivatives,or their salts,or esters

Method for manufacturing 3-halomethyl-3-cephem

PURPOSE: Provided is a method for manufacturing nitrobenzyl 7-phenoxyacet amido-3-halomethyl-3-cephem-4-carboxylate of the formula(I) useful as an intermediate in manufacturing cephalosporin antibiotics. CONSTITUTION: A method for manufacturing a compound of the formula(I), nitrobenzyl 7-phenoxyacet amido-3-halomethyl-3-cephem-4-carboxylate, is characterized by reacting a compound of the formula(III) with a halogenating agent and base, sequentially to give a compound of the formula(II), and reducing the compound of the formula(II), wherein X is a halogen such as chloride, bromine and the like.

Method of preparing unsaturated derivatives of 7-acylamido-3-cephem-4-carboxylic acid or their salts

Heteromonocyclic and heterobicyclic derivatives of unsaturated 7-ayclamide-3-cephem-4-carboxylic acid are disclosed, and process for preparing same. These compounds are suitable for treating infections caused by Gram-positive and Gram-negative microorganisms.

Patent SU414793A3

Process for preparing cephalosporins

Cephalosporins (I; R1=H, acyl; R2=residual group of nucleophilic compds.) were manufd. by reaction of compd. (II) with nucleophilic compd. Thus, 7-[D-5-(benzamido)adipinamido -3 (3`-oxobutyryloxy)methyl-e-cephem-4-carbonic acid reacted with 5-mercapto-1-methyl-1H-tetrazol and sodium hydrogen carbonate at 60≰C, the mixt. cooled, the pH adjusted to 1.5 with 4N-HCl to give 7-[D-5-(benzamide)adipinamido -3 (1 methyl-1H-tetrazol-5-yl)thiomethyl-3-cephem-4-carbonic acid.

Method of preparing cephalosporine derivatives or salts thereof

Method of obtaining derivatives of cephalosporine and their salts with metals or nitrogen-containing bases

A kind of Cefixime and refining methd

本发明涉及医药技术领域，尤其是一种头孢克肟及精制方法。该方法工艺简单，耗时短，不仅除杂效果好，而且仅用水作为反应溶剂，大大降低了工业化生产成本，无溶剂残留，提高了用药的安全性，且收率高，降低了对环境的污染。所得产品流动性好，产品质量高，一般精制后纯度可达99.70%以上，特别是聚合物可控制在0.10%以下，解决了目前国内市场所售产品普遍聚合物较高的问题。

The method of obtaining cephalosporin derivatives in the form of diastereoisomers or in the form of their mixture or in the form of acid-additive or additive with nitrogenous bases, except ammonium, or their metal salts

The method that cefalexin is separated in the reaction product of cefalexin is prepared from enzyme process

本发明涉及头孢氨苄制备领域，公开了从酶法制备头孢氨苄的反应产物中分离头孢氨苄的方法，该方法包括：(1)在0‑10℃的温度条件下，将所述反应产物通过40‑100目的筛网，得到含有头孢氨苄的滤出液和含有酶的截留物；(2)将所述滤出液的pH用酸调节至0.5‑2进行溶清，溶清后进行固液分离，得到含有头孢氨苄的液相；(3)将所述液相的pH用碱调节至3.5‑5.5进行结晶，得到含有头孢氨苄晶体的晶浆液。通过本发明的方法制备的头孢氨苄产品流动性好，且产品收率高。

Crystalline hydrate of oral cephalosporin and its composition

An antibacterial, 7β-[(Z)-2-(2-aminothiazol-4-yl)-4-carboxybut-2-enoylamino]-3-cephem-4-carboxylic acid is stable in a (di or tri)-hydrate crystal form. A pharmacologically effective amount of this hydrate is filled in a gelatin hard capsule sealed by a band of gelatin to make a stable composition for clinical use after storage for a long time.

Method for preparing crystalline hydrate of oral celphalosporin and its composition

An antibacterial, 7β-[(Z)-2-(2-aminothiazol-4-yl)-4-carboxybut-2-enoylamino]-3-cephem-4-carboxylic acid is stable in a (di or tri)-hydrate crystal form. A pharmacologically effective amount of this hydrate is filled in a gelatin hard capsule and sealed by a band of gelatin to make a stable composition for clinical use after storage for a long time.

Cephem-4-carboxylic acid derivatives

The cephene-4-carboxylic acid deriv. of formula (I) is prepd. by reacting an aldehyde cpd. of formula (II) with a phosphonium salt of formula (III) in the presence of a base and a solvent at 0-30 deg.C. In the formulas, R1 is methyl, ethyl, propyl, phenyl or benzyl; R2 is p-methoxy benzyl, diphenyl methyl or allyl; R3 is H, t- butoxy carbonyl or phenyl acetyl; R4 is H, t-butoxy carbonyl, formyl or phenyl acetyl. The solvent is pref. water, dichloromethane, ethylether and/or tetrahydrofurane. The deriv. of (I) is useful for antibiotics.

Novel salts in the production of cephalosporin antibiotics.

Patent SU399137A3

Preparation process of 7-(d-2-formyloxy-2-phenylacetamido)-3-(1-methyl-1h-tetrazole-5-ylthiomethyl)-3-cephem-4-carboxylic acid

Dissolve 7-amino-3-(1-phenyl-1H-tetrazole-5-ylthiomethyl)-3cephem-4- carboxylate.HCl (3.65g, 10m mole) in 1-methyl-2pyrrolidine (25ml), add trimethylchlorosilane (0.4mL, dehydrating agent) and slowly add O-fomylmandeloylchloride(2.38g, 12m mole) to former soln., stir for 80 mins at room temp.. Add rxn. mixt. to pre-cooled soln. (mixt. of water 50ml and ethylacetate 25ml), Sep. org. phase and evap. solvent by reduced distn. to give 4.8g (yield=98%) of the title compds. (I). The title compds. represent the wide range of antibacterial nature against gram pos. or neg. bacterial.

Process for preparing cephradine oxide D

本发明属于药物制备合成领域，具体涉及一种头孢拉定氧化物D的制备方法，将头孢拉定加入到水中，再加入高锰酸钾和乙酸，搅拌反应，反应结束后过滤，乙醚洗涤滤饼，烘干得到头孢拉定氧化物D。本发明以水为溶剂，绿色环保，高锰酸钾和乙酸为氧化剂，成本低，易除去，后处理简单，避免使用有机溶剂，反应温和，易于工业化生产。

Process for preparing cephalosporin compounds

A cephalosporin deriv. (I; R1 = H or acyl; R2 = residue of nucleophilic compd.) was prepd. by reaction of cephalosporanic acid ester (II; X = C6H5CH:, C6H4, CH3-CH-, -CH2CH2-) with nuclophilic compd. Formula II was obtained by acylation of 3-hydroxymethyl cephalosporanic acid with o-carboxymaleic anhydride or o-carboxysalicylic acid anhydride.

Method of preparing cephalosporin or salts thereof

Method for preparing cefalexin potassium monohydrate or cefalexin sodium crystalline monohydrate

Process for preparing derivatives of 3-oxyvinyl cephalosporin

New cephalosporins of the formula: <IMAGE> (I) in which n=0 or 1, R1 is a radical of the formula: <IMAGE> (II) [in which R4 is a protective radical and R5 is hydrogen, alkyl, vinyl, cyanomethyl or a protective radical], or R1 is a protective radical and R2 is a protective radical or an enzymatically removable radical, or R1 is an acyl radical which may be substituted in various ways and R2 is a protective radical, in the 3-oxoethyl-bicyclooct-2-ene or -bicyclooct-3-ene or 3-oxoethylidene-bicyclooctane form if n=0, and in the 3-oxoethyl-bicyclooct-2-ene or 3-oxoethylidene-bicyclooctane form if n=1, are useful as intermediates for the preparation of 3-thiovinyl-cephalosporins useful as antibacterial agents.

Method of producing 3-oxyvinylcephalosporin derivatives

New cephalosporins of the formula: <IMAGE> (I) in which n=0 or 1, R1 is a radical of the formula: <IMAGE> (II) [in which R4 is a protective radical and R5 is hydrogen, alkyl, vinyl, cyanomethyl or a protective radical], or R1 is a protective radical and R2 is a protective radical or an enzymatically removable radical, or R1 is an acyl radical which may be substituted in various ways and R2 is a protective radical, in the 3-oxoethyl-bicyclooct-2-ene or -bicyclooct-3-ene or 3-oxoethylidene-bicyclooctane form if n=0, and in the 3-oxoethyl-bicyclooct-2-ene or 3-oxoethylidene-bicyclooctane form if n=1, are useful as intermediates for the preparation of 3-thiovinyl-cephalosporins useful as antibacterial agents.

Method of producing crystalline form of cephalexin hydrochloride monohydrate

Crystalline cephalexin hydrochloride monohydrate, a useful antibiotic, can be prepared by the hydration of novel crystalline hydrochloride C 1-4 alkanol solvates.

Method for preparing derivatives of cephalosporin

New cephalosporins of the formula: <IMAGE> (I) in which n=0 or 1, R1 is a radical of the formula: <IMAGE> (II) [in which R4 is a protective radical and R5 is hydrogen, alkyl, vinyl, cyanomethyl or a protective radical], or R1 is a protective radical and R2 is a protective radical or an enzymatically removable radical, or R1 is an acyl radical which may be substituted in various ways and R2 is a protective radical, in the 3-oxoethyl-bicyclooct-2-ene or -bicyclooct-3-ene or 3-oxoethylidene-bicyclooctane form if n=0, and in the 3-oxoethyl-bicyclooct-2-ene or 3-oxoethylidene-bicyclooctane form if n=1, are useful as intermediates for the preparation of 3-thiovinyl-cephalosporins useful as antibacterial agents.

Method of preparing cephalosporin derivatives or salts thereof

Method of obtaining thieno(3,2-c)pyridine or derivatives thereof

New form crystal of cefathiamidine compound and preparation method of new crystal-form crystal

本发明提供了一种头孢硫脒化合物新晶型晶体，用X射线粉末衍射图谱和差式扫描量热数据描述其特征。在温度10～30℃的条件下，将纯度大于等于98％的头孢硫脒化合物溶解在溶剂中形成溶液，溶液浓度控制在0.02～0.15g/mL，再向溶液中滴加溶析剂，溶析剂体积用量为溶剂用量的1～3倍；加完溶析剂后悬浮3～5h，将所得的固液悬浮液分离，干燥，得到头孢硫脒化合物新晶型产品。所得产品结晶度高，晶型完整，产品纯度99％以上，过程收率89％以上；新晶型产品的热裂解温度比专利已经报道的晶型的热裂解温度更高，产品的热稳定性更好。

ANTIBACTERIAL COMPOSITIONS

Method of preparing cephalexine or salts thereof

Process for preparing 3-iodomethyl cephalosporins

A process is described for preparing a 3-iodomethyl cephalosporin of the formula which comprisesreacting in an aprotic solvent under substantially anhydrous conditions at a temperature between about 0°C and about 35°C a 3-alkanoylmethyl or 3-carbamoyloxymethyl cephalosporin oftheformula with a trialkylsilyl iodide of the formula where in the above formulas R is the residue of a carboxylic acid as defined in the specification; Ro is hydrogen or methoxy; R 1 is C 1 -C 4 alkyl, 2,2,2-trichloroethyl, iodomethyl, diphenylmethyl, benzyl, substituted benzyl substituted by methyl, methoxy or nitro; or R is a trialkylsilyl group of the formula wherein R 3 , R 3 , and R - 3 ; are independentlyC 1 -C 3 alkyl; orR 1 is sodium or potassium; R' 1 has the same meanings as R 1 , provided that, when R is sodium, potasstum. diphenylmethyl, or p-methoxybenzyl, R' 1 is R 2 is C 1 -C 4 alkanoyloxy or a carbamoyloxy group of the formula wherein R' 2 and R" 2 are independently hydrogen or C 1 -C 3 alkyl; and nis 0 or 1; with the limitation that when n is 1, the double bond represented by the dotted bonding lines is in the 3-position. The 3-iodomethyl cephalosporins are useful intermediates for antibiotics.

Antibacterial cephalosporins, pharmaceutical composition based on thereof and method of treatment

Изобретение относится к новым производным цефалоспорина общей формулы I, в которой R 1 обозначает водород или сложноэфирную группу, R 2 обозначает группу формулы (IIа, IIb, IIс), Y обозначает водород, алкил, замещенный алкил или ацил, R 4 обозначает водород, фенил, циклоалкил или алкил, R 5 обозначает водород, фенил, циклоалкил, низший алкил, насыщенный или ненасыщенный 5-6-членный гстероциклил, необязательно замещенный алкилом, трифторалкилом, оксо или аминогруппой, бензотиазолил или группу формулы (IId, IIe, IIf), R 7 обозначает алкил, R 8 обозначает водород, циклоалкил или алкил, R 9 обозначает водород или алкил, R 10 обозначает водород, алкил, замещенный алкил, где заместитель выбран из трифторалкила, пиридила, гидрокси, алкокси, галогена, амино или остатка сульфоновой кислоты; гидрокси, амино, фенил, алкенил, циклоалкил или группу формулы -N=CH-Phe, где Phe обозначает фенил, замещенный гидрокси, или R 9 и R 10 вместе с атомом азота обозначают насыщенный, ненасыщенный или замещенный 5-6-членный гетероциклил, содержащий один или два атома азота или кислорода, причем заместитель выбирают из формила или алкила и т.д. Соединение формулы IVa, R x представляет собой группу формулы -NН-С(СН 3 ) 3 и т.д., R y представляет собой NH, и R z представляет собой водород и т. д. Фармацевтическая композиция, предназначенная для лечения заболеваний, вызванных бактериями, содержит соединение формулы I в форме фармацевтически приемлемой соли или в свободной форме в комбинации с по меньшей мере одним фармацевтическим носителем или разбавителем. Способ лечения заболеваний, вызванных микробами, заключается в введении субъекту, нуждающемуся в таком лечении, эффективного соединений формулы I. Технический результат - получение новых антибактериальных цефалоспоринов. 4 с. и 9 з.п. ф-лы, 5 табл. I -O-Y IIa -N=R 6 IIc ССС Ьс ПЧ сэ (19) РОССИЙСКОЕ АГЕНТСТВО ПО ПАТЕНТАМ И ТОВАРНЫМ ЗНАКАМ ВИ” 2 183 212' ПМ С 070 501/46, А 64 К 31/546, 13) С2 А 61 Р 31/04 12) ОПИСАНИЕ ИЗОБРЕТЕНИЯ К ПАТЕНТУ ...

Crystalline solvate of cefuroxime acid

본 발명은 항생제 세푸록심 나트륨 염을 제조하는데 유용한 세푸록심 산의 결정성 용매화물에 관한 것이다. The present invention relates to crystalline solvates of cefuroxime acid useful for preparing the antibiotic cefuroxime sodium salt. 항생제, 세푸록심 산, 결정성 용매화물, 세푸록심 나트륨 염 Antibiotics, cefuroxime acid, crystalline solvate, cefuroxime sodium salt

Process for the preparation of 3-sulfonyloxy-3-cephem compounds

화학식 1로 나타내는 3-히드록시-3-세펨 화합물을 유기용매중 알칼리 금속탄산염 또는 알칼리토류 금속탄산염의 존재하에서, 화학식 2로 나타내는 술폰산할라이드 화합물과 반응시키는 것을 특징으로 하는, 화학식 3으로 나타내는 3-술포닐옥시-3-세펨 화합물의 제조방법. 3-hydroxy-3-cefem compound represented by Chemical Formula 1 is reacted with a sulfonic acid halide compound represented by Chemical Formula 2 in the presence of an alkali metal carbonate or an alkaline earth metal carbonate in an organic solvent. Process for the preparation of sulfonyloxy-3-cepem compound. (화학식 1) (Formula 1) (화학식 2) (Formula 2) (화학식 3) (Formula 3) (식중, R 1 ∼R 4 , X는 명세서 기재와 같음) (Wherein R 1 to R 4 , X are the same as those described in the specification)

3-vinyl-7- (thiazole methoxyimino) cephalosporanic acid crystal form and preparation method thereof

一种3‑乙烯基‑7‑(噻唑甲氧亚氨基)头孢烷酸晶型的制备方法，包括：S1：制备3‑乙烯基‑7‑(噻唑甲氧亚氨基)头孢烷酸的粗品；S2：制备所述粗品的磷酸盐；S3：将所述粗品的磷酸盐加入水溶液中，在1～5℃下，控制pH≤7.5；S4：加入碱溶解水溶液中的固体；加入活性炭；加入第一有机溶剂，调节pH＝3.5～7.0，达到析晶临界点；S5：加入第二有机溶剂，加入晶种析晶。本发明对粗品精制处理，控制温度、pH值、饱和度、分步加入有机溶剂，得到稳定性良好且具备抗菌性的3‑乙烯基‑7‑(噻唑甲氧亚氨基)头孢烷酸晶体。

The method of obtaining 7-aminocephalosporanic acid

7-acylamine-3-cephem-4-carboxylic acid derivative, its preparation and antimicrobial agent containing the same

(57)【要約】本公報は電子出願前の出願データであるた め要約のデータは記録されません。

Method of producing sodium salt of 7-/2,2-dimethyl-4(4-oxyphenyl)-5-oxo-1-imidazolinyl/-3-/1(z)-propenyl/-cef-3-em-4-carbolic acid

The antibiotic 7-[D-2-amino-2-(4-hydroxyphenyl)acetamido]-3-[(Z)-1-propenyl]ceph-3-em -4-carboxylic acid (BMY-28100) forms imidazolidinone derivatives on reaction with ketones. These derivatives are useful in pharmaceutical dosage forms and as intermediates for separation thereof from mixtures containing the [(E)-1-propenyl]isomer of the antibiotic.

Patent RU2016115906A3

ВУ“? 2016115906” АЗ Дата публикации: 30.09.2019 Форма № 18 ИЗПМ-2011 Федеральная служба по интеллектуальной собственности Федеральное государственное бюджетное учреждение 5 «Федеральный институт промышленной собственности» (ФИПС) ОТЧЕТ О ПОИСКЕ 1. . ИДЕНТИФИКАЦИЯ ЗАЯВКИ Регистрационный номер Дата подачи 2016115906/04(024973) 10.06.2010 Приоритет установлен по дате: [ ] подачи заявки [ ] поступления дополнительных материалов от к ранее поданной заявке № [Х] приоритета 10.06.2010 по первоначальной заявке № 2011152319 из которой данная заявка выделена [ ] подачи первоначальной заявки № из которой данная заявка выделена [ ] подачи ранее поданной заявки № [Х] подачи первой(ых) заявки(ок) в государстве-участнике Парижской конвенции (31) Номер первой(ых) заявки(ок) (32) Дата подачи первой(ых) заявки(ок) (33) Код страны 1. 12/482,373 10.06.2009 05 2. 200910141944.Х 10.06.2009 СМ Название изобретения (полезной модели): [Х] - как заявлено; [ ] - уточненное (см. Примечания) КОМПОЗИЦИИ ИЛИ ПРОЛЕКАРСТВА ПРОТИВОМИКРОБНЫХ И РОДСТВЕННЫХ ПРОТИВОМИКРОБНЫМ СОЕДИНЕНИЙ, ОБЛАДАЮЩИЕ ВЫСОКОЙ ПРОНИКАЮЩЕЙ СПОСОБНОСТЬЮ Заявитель: ТЕКФИЛДЗ БАЙОКЕМ КО.., ЛТД., СМ, ЮЙ Чунси, 0$ 2. ЕДИНСТВО ИЗОБРЕТЕНИЯ [Х] соблюдено [ ] не соблюдено. Пояснения: см. Примечания 3. ФОРМУЛА ИЗОБРЕТЕНИЯ: [Х] приняты во внимание все пункты (см. Примечания) [ ] приняты во внимание следующие пункты: [ ] принята во внимание измененная формула изобретения (см. Примечания) 4. КЛАССИФИКАЦИЯ ОБЪЕКТА ИЗОБРЕТЕНИЯ (ПОЛЕЗНОЙ МОДЕЛИ) (Указываются индексы МПК и индикатор текущей версии) Аб/1К 31/397 (2006.01) Аб1К 47/50 (2017.01) Аб1Р 33/10 (2006.01) Аб1К 31/43 (2006.01) Аб1Р 31/00 (2006.01) Аб/1К 31/545 (2006.01) Аб1Р 33/02 (2006.01) 5. ОБЛАСТЬ ПОИСКА 5.1 Проверенный минимум документации РСТ (указывается индексами МПК) Аб1К 31/397, Аб1К 31/43, Аб1К 31/545, Аб1К 47/50, Аб1Р 33/190, Аб1Р 31/00, Аб1Р 33/02 (2006.0 01 5.2 Другая проверенная документация в той мере, в какой она включена в поисковые подборки: 5.3 Электронные базы ...

Processes for manufacturing cephem derivatives

본 발명에 따르면, 구조식(2)의 화합물을 구조식(4)의 축합제 및 구조식(5)의 1-히드록시-6-트리플루오로메틸벤조트리아졸과 반응시킨 후 구조식(3)의 7-아미노세팔로스포란산(7-ACA) 또는 그 유도체와 아실화반응시키는 것을 특징으로 하는 하기 구조식(1)의 세펨 유도체의 제조방법이 제공된다. According to the present invention, the compound of formula (2) is reacted with the condensing agent of formula (4) and 1-hydroxy-6-trifluoromethylbenzotriazole of formula (5), followed by 7- Provided is a method for preparing a cefem derivative of Structural Formula (1) below, which is subjected to acylation with aminocephalosporanic acid (7-ACA) or a derivative thereof. 본 발명의 방법에 따르면 유기산(2)의 아민기를 보호하지 않고 온화한 온도조건에서 반응성 유도체로 전환시킨 후 이를 직접 아실화 반응시켜 고순도의 목적물을 수득할 수 있으므로 종래의 방법에 비해 경제적이며 산업화에 유리하다. According to the method of the present invention, since the amine group of the organic acid (2) can be converted into a reactive derivative under mild temperature conditions and then directly acylation reaction to obtain a high-purity target product, it is more economical than conventional methods and is advantageous for industrialization. Do.

Bicyclic beta-lactam/paraben complexes

本发明提供上列通式的复合物，其中：X是氯、氢、乙烯基或-CH 3 ；Z是CH 2 、S或O；n是0～5；Y是苯基或1，4-环己二烯-1-基；R 1 和R 2 是氢或羟基，但其条件是R 1 和R 2 不能同时是氢；而R 3 是-COO-、-COO(C 1 -C 4 烷基)、-NO 2 或-CO-R 4 ，其中R 4 是C 1 -C 4 烷基。

A kind of preparation method of Mandokef sodio-derivative

本发明涉及一种头孢孟多酯钠衍生物的制备方法，以化合物1为起始原料，经硅烷化保护后，与D‑(‑)‑O‑甲酰基扁桃酸酰氯进行酰化反应，然后经水解、分层得到头孢孟多酯钠衍生物1，其中，所述的化合物1的结构式为： 所述的头孢孟多酯钠衍生物1的结构式为： 所述的R 1 为碳原子数为1～3的烷基或碳原子数为1～3的烷羟基。本发明的制备方法能够高收率获得头孢孟多酯钠衍生物，为头孢孟多酯钠相关药学研究提供帮助，同时为合成新的头孢类结构化合物提供一种思路。

Enzymatic process for 3-substituted cephalosporins

3-Substd.-3-cephem-4-carboxylic acids of formula (I) are prepd. by contacting a 2beta-methyl-2alpha-substd. phenam-3-carboxylic acid of formula (II) with a deacetoxycephalosphorin C synthetase in an aq. medium at 20-40≰C and pH 6-9 in the presence of O2, Fe+2, ascorbate and alpha-ketoglutarate. In the formulas, R is 3- carboxyphenylacethyl or adipoyl; R1 is C1-3 alkyl, C1-3 alkoxy or C2-4 alkenyl.

Ceftibuten pharmaceutical composition for treating surgical infection

本发明属于医药技术领域，公开了一种治疗外科手术感染的药物头孢布烯组合物。所述的组合物由头孢布烯、精氨酸组成；所述的头孢布烯晶体化合物的结构式如式(I)所示，该晶体化合物用粉末X射线衍射测定法测定，以2θ±0.2°衍射角表示的X射线粉末衍射图谱如图1所示。本发明药物组合物不仅纯度高、杂质含量低、澄明度好，而且能保证生产中的分装效率、装量差异小，不良反应发生率大大降低，稳定性更好。 式（Ⅰ）。

Method of preparing unsaturated derivatives of 7-acylamido-3-cephem-4-carboxalic acid or their esters or their alkaline metal salts

Heteromonocyclic and heterobicyclic derivatives of unsaturated 7-ayclamide-3-cephem-4-carboxylic acid are disclosed, and process for preparing same. These compounds are suitable for treating infections caused by Gram-positive and Gram-negative microorganisms.

Process for preparation of crystalline half-hydrade of cefadroxyl

The invention relates to a novel crystalline cefadroxyl hemihydrate having a K.F. between about 3.5 and 2.0% : such compound is more stable than other cefadroxyl molecules. The novel cefadroxyl is obtained preparing and isolating a novel cefadroxil solvate of dimethylacetamide, or of N-methyl-2--pyrrolidone or of monomethylformamide, slurrying said solvate with a mixture methanol/isopropyl alcohol 30:70 to 70:30 by volume in the presence of from 5% to 12% of water a temperature of about +45 DEG C to + 55 DEG C and then filtering the so obtained compound.

Method of preparing cephalosporin compounds

New cyanomethylthioacetylcephalosporins of the following general formula, and their salts WHEREIN R is hydrogen, lower alkyl, aralkyl, tri(lower alkyl)silyl, a salt forming ion or the group ; R1 and R2 each is hydrogen, lower alkyl, lower alkenyl, aryl or aralkyl, each of which may be substituted, or R1 and R2 may together complete a carbocyclic ring; R3 is hydrogen, lower alkyl, lower alkenyl, cyclo-lower alkyl, unsaturated cyclo-lower alkyl, aryl, aralkyl or a heterocyclic group; R4 is lower alkyl, aryl or aralkyl and X is hydrogen, hydroxy, lower alkanoyloxy, lower alkoxy, lower alkylthio, aroyloxy, aralkanoyloxy, the radical of a nitrogen base, a quaternary ammonium radical or together X and R represent a bond linking carbon and oxygen in a lactone ring; are useful as antibacterial agents.

Process for preparing derivatives of cephalosporin,or their alkali metal salts,or their esters (modifications)

Beschrieben werden neue Cephalosporine der allgemeinen Formel I worin Y Wasserstoff oder Methoxy bedeutet, A sofern Y die Methoxygruppe darstellt, die Phenyl-, 4-Hydroxyphenyl-, 3,4-Dihydroxyphenyl- oder die 2- oder 3-Thienylgruppe bedeutet oder, sofern Y Wasserstoff oder die Methoxygruppe darstellt, eine Gruppe der Formel worin A' Wasserstoff, eine Halogenacetyl-, die Formyl- oder Tritylgruppe bedeutet, D Wasserstoff, die Acetoxy- oder Aminocarbonyloxygruppe, die Pyridinium- oder 4-Aminocarbonylpyridiniumgruppe oder die Gruppe -SHet bedeutet, worin Het ein gegebenenfalls substituierter Thiadiazol-, 4H-5,6-Dioxo-1,2,4-triazinyl- oder ein Tetrazolylrest darstellt, R die Gruppe -NHR 2 bedeutet, worin R 2 ein gegebenenfalls substituierter Pyridyl-, Pyrimidinyl-, Thienyl-, Furyl-, Thienylmethyl-, Imidazolylmethyl-, Thiazolylmethyl-, Pyridylmethyl- oder Pyrimidinylmethylrest sein kann und E Wasserstoff oder eine Schutzgruppe bedeutet, und ihre Salze mit anorganischen oder organischen Basen. Die Verbindungen besitzen eine sehr starke antibakterielle Wirkung.

Method of preparing cephalosporin derivatives or their salts with alkali metals or nitrogen bases