84957-29-9

Basic information

• Product Name: Cefpirome
• Synonyms: CEFPIROME;CEFPIROME SULPHATE;1-[[(6R,7R)-7-[2-(2-amino-4-thiazolyl)glyoxylamido]-2-carboxy-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-en-3-yl]methyl]-6,7-dihydro-5H-1-pyrindinium hydroxide, inner salt, 72-(Z)-(O-methyloxime);3-[(2,3-cyclopenteno-1-pyridinium)methyl]-7-[2-syn-methoxyimino-2-(2-aminothiazol-4-yl)acetamido]ceph-3-em-4-carboxylate;HR-810;Keitim;(6R,7R)-7-(()-2-(2-Amino-4-thiazolyl)-2-methoxyiminoacetamido)-8-oxo-3-(2beta-trimethylenpyridinio)methyl)-5-thia-1-azabicyclo(4.2.0)oct-2-en-2-carboxylat;1-(((6R,7R)-7-(2-(2-Amino-4-thiazolyl)glyoxylamino)-2-carboxy-8-oxo-5-thia-1-azabicyclo(4.2.0)oct-2-en-3-yl)methyl)-6,7-dihydro-5H-1-pyridinium hydroxide, inner salt
• CAS NO: 84957-29-9
• Molecular Formula: C₂₂H₂₂N₆O₅S₂
• Molecular Weight: 514.58
• EINECS: 1592732-453-0
• Product Categories: Cefpirome;Pharmaceutical intermediate
• Mol File: 84957-29-9.mol
• Article Data: 4

Chemical Properties

• Appearance: powder
• Storage Temp.: 2-8°C(protect from light)
• CAS DataBase Reference: Cefpirome(CAS DataBase Reference)
• NIST Chemistry Reference: Cefpirome(84957-29-9)
• EPA Substance Registry System: Cefpirome(84957-29-9)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38-42/43
• Safety Statements: 22-26-36/37/39
• Hazardous Substances Data: 84957-29-9(Hazardous Substances Data)

Usage

Description

This drug is resistant with respect to a broad spectrum of beta-lactamases. Its spectrum of activity is analogous to that of the third-generation cephalosporin cefotaxime (32.1.2.56), although it is more active with respect to some staphylococci, enterococci, and also a few enterobacteria. Synonyms of this drug are cefrom, cedixen, and others.

Uses

Cephalosporin antibiotic Claforan

Brand name

Cefrom (Hoechst-Roussel).

Antimicrobial activity

A semisynthetic aminothiazoyl cephalosporin formulated as the sulfate for parenteral administration. Activity against common pathogens is similar to that of cefotaxime and ceftriaxone, but it is more active against Ps. aeruginosa. Unlike other cephalosporins it exhibits activity against some strains of enterococci (MIC 4–16 mg/L), but this is of doubtful clinical benefit. It is generally very stable to β-lactamases. It is active against strains of Enterobacter spp., Citrobacter spp., Hafnia spp., Providencia spp., Ser. marcescens and Pr. vulgaris producing molecular class C cephalosporinases. Sten. maltophilia is resistant. A 1 g intramuscular injection produces a plasma concentration of 25 mg/L after 1.6–2.3 h. A similar intravenous dose achieves a peak concentration of 97 mg/L. The plasma half- life is 1.4–2.3 h and protein binding is around 10%. It is well distributed, achieving therapeutic concentrations in tissues and exudates. It penetrates poorly into CSF in the absence of meningeal inflammation, but concentrations around 2–4 mg/L have been found in patients with purulent meningitis. Little, if any, of the drug is metabolized and most is excreted unchanged in the urine within 12 h, mainly by glomerular filtration. Clearance declines in proportion to renal function. Around 60% of the drug is removed in 3 h by hemodialysis. Low concentrations are found in breast milk. Side effects are those common to other cephalosporins. Diarrhea is common and occasional cases of pseudomembranous colitis have been reported. It is mainly used in the treatment of serious sepsis, particularly nosocomial infections in which resistant Gram-negative pathogens are known or suspected to be involved. It is not widely available, but is marketed in Japan.

Clinical Use

Cefpirome (Cefrom) is a newer parenteral, -lactamase–resistant cephalosporin with a quaternary ammonium groupat the 3-position of the cephem nucleus. Because its potencyagainst Gram-positive and Gram-negative bacteria rivals thatof the first-generation and third-generation cephalosporins,respectively, cefpirome is being touted as the first fourthgenerationcephalosporin. Its broad spectrum includesmethicillin-sensitive staphylococci, penicillin-resistantpneumococci, and β-lactamase–producing strains of E. coli,Enterobacter, Citrobacter, and Serratia spp. Its efficacyagainst P. aeruginosa is comparable with that of ceftazidime.Cefpirome is excreted largely unchanged in the urine with ahalf-life of 2 hours.

Synthesis

Cefpirome, {6R-[6α,7β(Z)]}-1-[(7-{[(2-amino-4-thiazolyl)-(methoximino) acetyl]amino}-2-carboxy-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-en-3-yl)methyl- 1-methyl]pyrrolidine chloride (32.1.2.100), is also synthesized by methods described for synthesizing third-generation cephalosporins, in particular, ceftazidime (32.1.2.82).

InChI:InChI=1/C22H22N6O5S2/c1-33-26-15(13-10-35-22(23)24-13)18(29)25-16-19(30)28-17(21(31)32)12(9-34-20(16)28)8-27-7-3-5-11-4-2-6-14(11)27/h3,5,7,10,16,20H,2,4,6,8-9H2,1H3,(H3-,23,24,25,29,31,32)/b26-15-/t16-,20+/m1/s1

Upstream product

• 63527-52-6 cefotaxime 
• 533-37-9 2,3-cyclopentenopyridine 
• 83421-24-3 7β-<2-(2-aminothiazol-4yl)-2-(Z)-methoximinoacetamide>-3-iodomethyl-2-<(trimethylsilyloxy)carbonyl>cephalosporin 
• 86070-92-0 (6R,7R)-7-{2-(2-Amino-thiazol-4-yl)-2-[(Z)-methoxyimino]-acetylamino}-3-iodomethyl-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid 
• 101156-40-5 (6R,7R)-4-methoxybenzyl-3-(iodomethyl)-8-oxo-7-(2-phenylacetamido)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate 
• 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 
• 87314-56-5 7-amino<3-(2,3-cyclopentenopyridinium)methyl>ceph-3-em-4-carboxylate 
• 95055-53-1 C₂₄H₂₃N₃O₄S 
• 1273319-61-1 p-methoxybenzyl 7-phenylacetamido-3-(2,3-cyclopenteno-1-pyridinio)-3-cephem-4-carboxylate iodide 
• 104498-86-4 C₁₉H₂₅N₅O₇S₂Si 
• 65872-41-5 cefotaxime 

Downstream Products

• 98753-19-6 cefpirome Sulfate 
• 123176-07-8 2,4-dinitrophenylhydrazone of 2-<(Z)-2-(2-amino-4-thiazolyl)-2-methoxyiminoacetamido>acetaldehyde 
• 130431-30-0 epi-cefpirome 
• 97164-55-1 cefpirome 
• 124667-22-7 Δ₂-cefpirome 
• 130468-09-6 2-<<(2-amino-4-thiazolyl) ((Z)-methoxyimino)acetyl>aminomethyl>-1,2,5,7-tetrahydro-7-oxo-4H-furo<3,4-d> <1,3>thiazine 
• 533-37-9 2,3-cyclopentenopyridine 
• 104301-63-5 2-<<(2-amino-4-thiazolyl)((Z)-methoxyimino)acetyl>amino>acetoaldehyde 

Relevant articles and documents

One-pot synthesis of cefpirome sulfate from GCLE

Cefpirome was synthesized in 37.7% overall yield from 3-chloromethyl-7- phenylacetylamino cephalosporanic acid p-methoxybenzyl ester (GCLE) by sequential substitution of C-3 chloride with iodide and 2,3- cyclopentenopyridine, followed by a one-pot procedure including deprotection of carboxyl group, hydrolysis of 7-phenylacetamido, and reaction with 2-mercaptobenzothiazolyl-(Z)-2-(2-aminothiazol-4-yl)-2-methoxyiminoacetate (MAEM). The reaction conditions were as follows: obtained from GCLE at low temperature (-5 to 0°C) and absence of light, 3-iodomethyl-7- phenylacetylamino cephalosporanic acid p-methoxybenzyl ester (GILE) without purification was reacted directly with 2,3-cyclopentenopyridine, in which the molar ratio of GCLE, NaI, and 2,3-cyclopentenopyridine was 1:2:4, and the molar ratio of the resulting compound p-methoxybenzyl 7-phenylacetylamido-3-(2,3- cyclopenteno-1-pyridinio)methyl-3-cephem-4-carboxylate iodide and MAEM was 1:1.1. The structure of the intermediate and the target compound obtained were determined by nuclear magnetic resonance spectra and mass spectroscopy.

Synthesis and biological evaluation of a series of parenteral 3'-quaternary ammonium cephalosporins

The preparation and biological evaluation of a series of 7β-[2-(2-aminothiazol-4-yl)-2(Z)-methoximinoacetamido]cephalosporins, substituted at the 3'-position with monocyclic or bicyclic nitrogen-containing heterocycles are described. The resulting family of parenteral compounds displays a broad spectrum of antibacterial activity. Some compounds exhibit a similar level of Gram-negative activity to that of the 'third-generation' cephalosporins with increased staphylococcal activity. The in vitro and in vivo antimicrobial activity, structure-activity relationships, β-lactamase stability, and in vitro and in vivo pharmacological evaluations are presented.