117467-28-4

Basic information

• Product Name: Cefditoren pivoxil
• Synonyms: (6r-(3(z),6-alpha,7-beta-(z)))-dimethyl-1-oxopropoxy)methyleste;MEIACT;ME-1207;CEFDITOREN;CEFDITOREN PIVALOYLOXYMETHYL ESTER;CEFDITOREN PIVOXIL;CefditorenPivoxil,ME-1207,Meiact;(6R,7R)-7-[[(2Z)-(2-Amino-4-thiazolyl)methoxyimino)acetyl]amino]-3-[(1Z)-2-(4-methyl-5-thiazolyl)ethenyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic Acid Pivaloyloxymethyl Ester
• CAS NO: 117467-28-4
• Molecular Formula: C₂₅H₂₈N₆O₇S₃
• Molecular Weight: 620.72
• EINECS: 1308068-626-2
• Product Categories: Intermediates & Fine Chemicals;Pharmaceuticals;Sulfur & Selenium Compounds;Cefditoren;CYMBALTA
• Mol File: 117467-28-4.mol
• Article Data: 15

Chemical Properties

• Melting Point: 207-209°C
• Appearance: off-white powder
• Density: 1.55 g/cm³
• Refractive Index: 1.71
• Storage Temp.: -20?C Freezer
• Solubility: DMSO (Slightly), Ethanol (Slightly), Methanol (Slightly, Heated)
• PKA: 8.08±0.60(Predicted)
• Merck: 14,1921
• CAS DataBase Reference: Cefditoren pivoxil(CAS DataBase Reference)
• NIST Chemistry Reference: Cefditoren pivoxil(117467-28-4)
• EPA Substance Registry System: Cefditoren pivoxil(117467-28-4)

Safety Data

• RTECS: XI0367800
• Hazardous Substances Data: 117467-28-4(Hazardous Substances Data)

Usage

Description

Cefditoren pivoxil, also known as Meiact, is an orally bioavailable third-generation cephalosporin antibiotic. It is a prodrug of cefditoren, which is hydrolyzed by intestinal wall esterases to form the active compound. Cefditoren pivoxil is characterized by its off-white powder form and exhibits a broad-spectrum of activity against both Gram-positive and Gram-negative bacteria. It is more potent than many other existing agents of its class and shows the highest therapeutic activity against S. pneumoniae and S. marcescens infections. The drug is effective in treating a broad range of bacterial infections, including dermatological and other community-acquired infections, and is known for its resistance to β-lactamase hydrolysis, low toxicity, and minimal side effects.

Uses

Used in Pharmaceutical Industry:
Cefditoren pivoxil is used as an antibacterial agent for the treatment of a wide range of bacterial infections. Its broad-spectrum activity makes it effective against both Gram-positive and Gram-negative bacteria, including systemic infections caused by S. aureus, E. coli, K. pneumoniae, P. mirabilis, and S. marcescens.
Used in Respiratory Infections Treatment:
Cefditoren pivoxil is used as an antibiotic for the treatment of acute bacterial exacerbations of chronic bronchitis and community-acquired pneumonia. Its effectiveness in these respiratory infections is attributed to its broad-spectrum activity and resistance to β-lactamase hydrolysis.
Used in Dermatological Infections Treatment:
Cefditoren pivoxil is used as an antibacterial agent for the treatment of various dermatological infections caused by susceptible bacteria. Its broad-spectrum activity and low toxicity make it a suitable choice for treating skin infections.

Originator

Meiji Seika (Japan)

Manufacturing Process

A mixture of THF (250 ml) and water (150 ml) was stirred under inert atmosphere. At 0°-1°C, 7-amino-3-[(Z)-2-(methyl-5-thiazolyl)vinyl]-3-cephem-4-carboxylic acid (25.0 g) and 2-mercapto-5-phenyl-1,3,4- oxadiazolyl-(Z)-2-(2-aminothiazol-4-yl)-2-methoxyimino acetate (33.3 g) were added. Triethylamine (10.5 g) was slowly added to reaction by maintaining the pH between 7.5 to 8.5. The reaction was monitored by HPLC. After 4-5 hrs., the reaction mixture was extracted by methylene chloride. The aqueous layer is subjected for charcoal (0.125 g) treatment. Ethylacetate was added to the filtrate and the solution was acidified with diluted HCl at 10°C to pH 3.0. The solid separated was filtered, washed with water and ethylacetate and then dried under vacuum at 40-45°C to get 3-[(Z)-2-(4-methyl-5-thiazolyl)vinyl]-7- [(Z)-(2-aminothiazolyl-4-yl)-2-(methoxyimino)acetamido]-3-cephem-4- carboxylic acid (Cefditoren acid), 35.0 g (yield 90%), HPLC (purity)=96-98%.In practice it is often used as Cefditoren pivoxil.

Therapeutic Function

Antibiotic

Antimicrobial activity

It exhibits good activity against staphylococci, streptococci (but not enterococci), H. influenzae and M. catarrhalis, including β-lactamase-producing strains. Isolates of Str. pneumoniae exhibiting reduced susceptibility to penicillin are less susceptible (MIC 0.125–2 mg/L). Most enterobacteria, including many Enterobacter, Citrobacter, Serratia and Proteus spp., are susceptible. It is not active against Ps. aeruginosa, Sten. maltophilia or atypical respiratory pathogens such as Chlamydophila pneumoniae and M. pneumoniae. It is stable to staphylococcal and common enterobacterial β-lactamases.

Pharmacokinetics

Oral absorption: c. 70% Cmax 200 mg oral: c. 1.8 mg/L after 1.5–3 h Plasma half-life: 0.8–1.3 h Volume of distribution: 9.3 L Plasma protein binding: 88% After oral administration the pivaloyl ester is rapidly cleaved by esterases in the gut wall. Ingestion with food improves the bioavailability. Plasma concentrations are raised in elderly patients. There is no accumulation on repeated dosing. It is excreted unchanged in the urine with a half-life of around 1.5 h, achieving a concentration of 150–200 mg/L within 4 h. Dosage adjustment is recommended in patients with deteriorating renal function.

Clinical Use

It has been advocated for community-acquired upper and lower respiratory tract infections and skin infections.

Side effects

In common with other pivoxil esters it may cause carnitine deficiency. Other side effects are those common to cephalosporins, mainly gastrointestinal disturbance.

InChI:InChI=1/C25H28N6O7S3/c1-12-15(41-10-27-12)7-6-13-8-39-21-17(29-19(32)16(30-36-5)14-9-40-24(26)28-14)20(33)31(21)18(13)22(34)37-11-38-23(35)25(2,3)4/h6-7,9-10,17,21H,8,11H2,1-5H3,(H2,26,28)(H,29,32)/t17-,21-/m1/s1

Upstream product

• 64485-90-1 2-(2-aminothiazol-4-yl)-2-(methoxy)iminoacetic acid 
• 64485-89-8 ethyl (Z)-2-(methoxyimino)-2-[2-(triphenylmethyl)-aminothiazol-4-yl]acetate 
• 155723-02-7 (6R,7R)-7-amino-3-[(1Z)-2-(4-methyl-5-thiazolyl)vinyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid 
• 64485-88-7 ethyl 2-(2-aminothiazol-4-yl)-2-(anti)-methoxyiminoacetate 
• 53064-79-2 iodomethyl pivaloate 
• 957-68-6 7-Aminocephalosporanic acid 
• 80756-85-0 (Z)-S-benzo[d]thiazol-2-yl 2-(2-aminothiazol-4-yl)-2-(methoxyimino)ethanethioate 
• 104145-95-1 cefditoren 
• 104146-53-4 7-<(Z)-2-(2-Aminothiazol-4-yl)-2-methoxyiminoacetamido>-3(Z)-(4-methylthiazol-5-yl)vinyl-3-cephem-4-carboxylic acid sodium salt 
• 138514-31-5 7-phenylacetamido-3-[(Z)-2-(4-methyl-5-thiazolyl)ethenyl]-4-aminocephalosporanic acid p-methoxybenzylester 
• 119608-99-0 p-Methoxybenzyl 7-amino-3(Z)-(4-methylthiazol-5-yl)vinyl-3-cephem-4-carboxylate 
• 138450-73-4 p-Methoxybenzyl 7-<(Z)-2-(2-tritylaminothiazol-4-yl)-2-methoxyiminoacetamido>-3(Z)-(4-methylthiazol-5-yl)vinyl-3-cephem-4-carboxylate 
• 119636-62-3 [(6R,7R)-2-(4-Methoxy-benzyloxycarbonyl)-8-oxo-7-phenylacetylamino-5-thia-1-aza-bicyclo[4.2.0]oct-2-en-3-ylmethyl]-triphenyl-phosphonium; iodide 
• 104146-10-3 (6R,7R)-3-Chloromethyl-8-oxo-7-phenylacetylamino-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid 4-methoxy-benzyl ester 

Relevant articles and documents

Preparation method of cefdiaxone pivoxil

The invention relates to a preparation method of Cefditoren Pivoxil. The preparation method comprises steps as follows: 7-ACA (3-acetyloxymethyl-5-thio-7-amino-8-oxy-1-nitrogen heterobicyclic octyl-2-ene-2 carboxylic acid) is taken as a starting raw material and is subjected to iodination and Wittig reaction after silanization protection, and a Cefditoren parent nucleus 7-ATCA (7-amino-3-[(Z)-2-(4-methyl-5-thiazole) vinyl]-3-cephem-4-carboxylic acid) is generated; after amino protection of aminothiazole ethyl gallate, a compound 2 is produced from 7-ATCA under catalysis of AlMe3; the compound2 is subjected to an esterification reaction with iodomethyl pivalate under actions of a phase transfer catalyst and an acid adsorbent, the amino protection is removed, and a target product CefditorenPivoxil is obtained. According to the preparation method, reaction conditions are mild, product purity and yield are high, the process is stable, amplification is easy, and the method is applicable to industrial production.

Preparation method of cefditoren pivoxil

The invention relates to a preparation method of cefditoren pivoxil. The preparation method comprises the following steps: 7-aminocephalosporanic acid(ACA) is taken as a starting material and subjected to a series of reactions such as iodination and the like after silylation protection to generate parent nucleus for cefditoren, namely 7-amino-3-[(Z)-2-(4-methyl-5-thiazolyl)ethenyl]-3-cephem-4-carboxylic acid (7-ATCA); the compound 7-ATCA firstly reacts with sodium iso-octoate to form sodium salt and then reacts with ethyl 2-(2-aminothiazole-4-yl)-2-methoxyiminoacetate to generate a compound 2,namely cefditoren sodium, under the catalysis of immobilized penicillin acylase; and then the cefditoren sodium reacts with iodomethyl pivalate to obtain a target product, namely cefditoren pivoxil.The preparation method is mild in reaction conditions, environmentally-friendly, high in conversion rate, simple in process, high in content of cis isomers, easy to enlarge and suitable for industrialproduction.

A spore proper logical sequence of the ester preparation method

The invention belongs to the technical field of medicines and particularly relates to a preparation method of cefditoren pivoxil. The preparation method particularly includes following steps: (1) carrying out a reaction between cefditoren mother nucleus 7ATCA and AE-activated ester with dichloromethane as a solvent under an alkaline condition at 0-5 DEG C; (2) performing extraction with pure water and adding a sodium iso-octoate/acetone solution to obtain cefditoren sodium; (3) carrying out a reaction between the cefditoren sodium and iodomethyl pivalate under the alkaline condition at -40 DEG C to obtain a cefditoren pivoxil solution; (4) adding pure water to separate out a crystal to obtain a crude product of the cefditoren pivoxil. The technical scheme also comprises steps of dissolving the crude product of the cefditoren pivoxil in a mixed solution including dichloromethane and anhydrous ethanol, washing the material solution with a 1% sodium bicarbonate solution and pure water, collecting an organic phase, and performing a pressure-reducing evaporate-drying process to obtain the cefditoren pivoxil being higher than 99% in purity and less in impurities. The preparation method is simple in operation, is easy to control, is high in yield, allows the raw material to be obtained easily and is suitable for industrialized large-scale production.