ChemicalBook--->CAS DataBase List--->73384-59-5


73384-59-5 Structure

73384-59-5 Structure

(6R,7R)-7-[[(2E)-2-(2-Amino-1,3-thiazol-4-yl)-2-methoxyiminoacetyl]amino]-3-[(2-methyl-5,6-dioxo-1H-1,2,4-triazin-3-yl)sulfanylmethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid


Ceftriazone sodium(Sterile)
5-Thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid, 7-[[(2-amino-4-thiazolyl)(methoxyimino)acetyl]amino]-8-oxo-3-[[(1,2,5,6-tetrahydro-2-methyl-5,6-dioxo-1,2,4-triazin-3-yl)thio]methyl]-, [6R-[6α,7β(Z)]]-
5-Thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid, 7-[[(2Z)-(2-amino-4-thiazolyl)(methoxyimino)acetyl]amino]-8-oxo-3-[[(1,2,5,6-tetrahydro-2-methyl-5,6-dioxo-1,2,4-triazin-3-yl)thio]methyl]-, (6R,7R)-
(6R,7R)-7-[[(2E)-2-(2-Amino-1,3-thiazol-4-yl)-2-methoxyiminoacetyl]amino]-3-[(2-methyl-5,6-dioxo-1H-1,2,4-triazin-3-yl)sulfanylmethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
(6R,7R)-7-[[(Z)-(2-Amino-4-thiazolyl)(methoxyimino)acetyl]amino]-8-oxo-3-[[(2,5-dihydro-6-hydroxy-2-methyl-5-oxo-1,2,4-triazin-3-yl)thio]methyl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
(6R,7R)-7-[2-(2-Amino-4-thiazolyl)-2-[(Z)-methoxyimino]acetylamino]-3-[[(2,5-dihydro-6-hydroxy-2-methyl-5-oxo-as-triazin-3-yl)thio]methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
Antibiotic Ro-13-9904

[Molecular Formula]

[MDL Number]

[Molecular Weight]

[MOL File]

Chemical PropertiesBack Directory
[Melting point ]

155 °C
[density ]

1.96±0.1 g/cm3(Predicted)
[storage temp. ]

Keep in dark place,Sealed in dry,2-8°C
[solubility ]

DMSO (Slightly), Methanol (Slightly)
[form ]


pKa –3.2±0.6 (Uncertain);–1.8±0.2 (Uncertain);2.57±0.50 (Uncertain);2.90±0.50 (Uncertain);8.03±0.40 (Uncertain)
[color ]

Off-White to Pale Yellow
[CAS DataBase Reference]

73384-59-5(CAS DataBase Reference)
[EPA Substance Registry System]

73384-59-5(EPA Substance)
Safety DataBack Directory
[Hazard Codes ]

[Risk Statements ]

R42/43:May cause sensitization by inhalation and skin contact .
[Safety Statements ]

S22:Do not breathe dust .
S24:Avoid contact with skin .
S37:Wear suitable gloves .
S45:In case of accident or if you feel unwell, seek medical advice immediately (show label where possible) .
[HS Code ]

Raw materials And Preparation ProductsBack Directory
[Raw materials]

Benzaldehyde-->Methylhydrazine-->Chloroacetyl chloride-->Potassium thiocyanate-->thiosemicarbazide-->Silicon tetrahydride-->Methylhydrazine sulfate-->Dimethyl oxalate-->Activ Ester-->PIVALAMIDE-->Thiotriazinone-->7-ACT-->CARBOXYLIC ACID-->Formic acid
Hazard InformationBack Directory

Ceftriaxone has the same C-7 side-chain moiety as cefotaxime and ceftizoxime, but the C-3 side chain consists of a metabolically stable and activating thiotriazinedione in place of the normal acetyl group. The C-3 side chain is sufficiently acidic that at normal pH, it forms an enolic sodium salt; thus, the commercial product is a disodium salt.


Possible carcinogen. Packaged under nitrogen

This drug has a broad spectrum of antimicrobial action that includes the majority of the clinically significant microorganisms: Gram-positive, Gram-negative, aerobic, anaerobic, and blue-pus bacillus. It is resistant with respect to most beta-lactamases of Gram-positive and Gram-negative bacteria.
It is used for peritonitis, sepsis, meningitis, cholangitis, empyema of the gall bladder, pneumonia, lung abscesses, pyelonephritis, infections of the bones, joints, skin, soft tissues, abdominal and gynecological infections, and for infected wounds and burns. The main synonym of this drug is rocefin.

ChEBI: A cephalosporin compound having 2-(2-amino-1,3-thiazol-4-yl)-2-(methoxyimino)acetylamino and [(2-methyl-5,6-dioxo-1,2,5,6-tetrahydro-1,2,4-triazin-3-yl)sulfanyl]methyl side-groups.
[Manufacturing Process]

19 g of (6R,7R)-7-[2-[2-(2-chloroacetamido)-4-thiazolyl]-2-(methoxyimino) acetamido]-8-oxo-3-[[(1,4,5,6-tetrahydro-4-methyl-5,6-dioxo-as-triazin-3- yl)thio]methyl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid are suspended in 150 ml of water together with 9.5 g of thiourea. The pH is adjusted to 6.8 with 5% sodium hydrogen carbonate solution while gassing with nitrogen and stirring, there being obtained a yellow-orange solution. The pH of the solution is held constant at 6.8-7.0 for 6 hours by adding sodium hydrogen carbonate solution by means of an autotitrator. 100% formic acid is added to the orange colored solution until the pH is 3.5. The precipitated material is filtered off under suction and washed with 100 ml of 10% formic acid. This material is denoted as (1). The filtrate is adjusted to pH 2.5 by adding 100% formic acid, whereby additional substance precipitates out. The mixture is held in an ice-bath for 1 hour, the precipitated substance is then filtered off and washed with a small amount of ice-water. This material is denoted as fraction I. The aforementioned orange-brown material (1) is suspended in 250 ml of water. The suspension is adjusted to pH 7 with 2 N sodium hydroxide, there being obtained an orange-brown solution. Additional 100% formic acid is added to this solution until the pH is 3.5. The material which thereby precipitates out is filtered off under suction and discarded. The filtrate is adjusted to pH 2.5 with 100% formic acid, whereby additional substance precipitates out. The mixture is held in an ice-bath for 1 hour, the precipitated substance is then filtered off under suction and washed with a small amount of ice-water. This material is denoted as fraction II. Fractions I and II are suspended together in 500 ml of ethanol and evaporated in a rotary evaporator in order to remove water. After adding ether, the mixture is filtered under suction and the precipitate is washed successively with ether and low-boiling petroleum ether. There is thus obtained the title substance in the form of a yellowish solid material which is denoted as A.
The mother liquors and washings of fractions I and II are concentrated from a volume of about 1.7 liters to 250 ml, the pH is adjusted to 2.5 with 100% formic acid and the solution is stored overnight in a refrigerator, whereby further substance crystallizes. This is filtered off under suction and washed with a small amount of water. The residue on the suction filter is azeotropically distilled with ethanol. There is obtained solid, almost colorless title substance which is denoted as B. B is purer than A according to thin-layer chromatography.
In order to obtain pure title substance, the acid B is suspended in 150 ml of methanol and treated while stirring with 10 ml of a 2 N solution of the sodium salt of 2-ethylcaproic acid in ethyl acetate. After about 10 minutes, there results a solution which is treated with 100 ml of ethanol. The mixture is extensively concentrated at 40°C in vacuo. The sodium salt precipitates out in amorphous form after adding ethanol. This salt is filtered off under suction, washed successively with ethanol and low-boiling petroleum ether and dried at 40°C in a high vacuum. There is obtained the title substance in the form of an almost colorless amorphous powder.
[Therapeutic Function]

[Antimicrobial activity]

Most β-lactamase-producing enterobacteria are highly susceptible, as are streptococci (but not enterococci) and fastidious Gram-negative bacilli, although brucellae are less sensitive (MIC 0.25–2 mg/L). Treatment failure has been reported in tularemia. Ps. aeruginosa, mycoplasmas, mycobacteria and L. monocytogenes are resistant.
[Acquired resistance]

Ceftriaxone is hydrolyzed by some chromosomal enzymes, including those of Enterobacter spp. and B. fragilis. Derepression of chromosomal β-lactamase production can cause resistance in some species of Gram-negative bacilli in vitro and has been observed in patients.

Cmax 500 mg/L intramuscular: c. 40 mg/L after 2 h
1 g intravenous (15–30-min infusion): c. 120–150 mg/L end infusion
Plasma half-life: 6–9 h
Volume of distribution: 0.15 L/kg
Plasma protein binding: 95%
Ceftriaxone penetrates well into normal body fluids and natural and experimental exudates. In children treated for meningitis with 50 or 75 mg/kg intravenously over 10–15 min, mean peak CSF concentrations ranged from 3.2 to 10.4 mg/L, with lower values later in the disease. In patients receiving 2 g before surgery, concentrations in cerebral tissue reached 0.3–12 mg/L. In patients with pleural effusions of variable etiology given a 1 g intravenous bolus, concentrations of 7–8.7 mg/L were found at 4–6 h. In patients with exacerbations of rheumatoid arthritis receiving the same dose, joint fluid contained concentrations close to those in the serum, but with wide individual variation. Tissue fluid:serum ratios have varied from around 0.05 in bone and muscle to 0.39 in cantharides blister fluid. The apparent volume of distribution is increased in patients with cirrhosis where the drug rapidly enters the ascitic fluid, but its elimination kinetics are unaffected.
Ceftriaxone rapidly crosses the placenta, maternal doses of 2 g intravenously over 2–5 min producing mean concentrations in cord blood of 19.5 mg/L, a mean cord:maternal serum ratio of 0.18; and in amniotic fluid 3.8 mg/L, a fluid:maternal serum ratio of 0.04. The plasma elimination half-life appears to be somewhat shortened in pregnancy (5–6 h). Some appear in the breast milk, the milk:serum ratio being about 0.03–0.04, secretion persisting over a long period with a half-life of 12–17 h.
Metabolism and excretion
Ceftriaxone is not metabolized. Biliary excretion is unusually high, 10–20% of the drug appearing in the bile in unchanged form, with concentrations up to 130 mg/g in biopsied liver tissue from patients receiving 1 g intravenously over 30 min. The insoluble calcium salt may precipitate in the bile leading to pseudolithiasis. About half the dose appears in the urine over the first 48 h, somewhat more (c. 70%) in neonates. Excretion is almost entirely by glomerular filtration, since there is only a small effect of probenecid on the excretion of the drug. The half-life is not linearly correlated with creatinine clearance in renal failure and, in keeping with the low free plasma fraction, it is not significantly removed by hemodialysis. The volume of distribution is not affected by renal failure.
[Clinical Use]

Uses of Ceftriaxone are similar to those of cefotaxime, the long half-life offering the advantage of once-daily administration. It is used in the treatment of acute bacterial meningitis and as an alternative to rifampicin (rifampin) in the prophylaxis of meningococcal disease.
[Side effects]

Reactions are those common to other cephalosporins. Mention has been made of thrombocytopenia, thrombocytosis, leukopenia, eosinophilia abdominal pain, phlebitis, rash, fever and increased values in liver function tests. Diarrhea is common and suppression of the aerobic and anaerobic fecal flora has been associated with the appearance of resistant bacteria and yeasts.
Biliary pseudolithiasis due to concretions of insoluble calcium salt has been described in adults but principally in children. The precipitates can be detected in a high proportion of patients by ultrasonography and can occasionally cause pain, but resolve on cessation of treatment. Ceftriaxone is better avoided in patients with pre-existing biliary disease, but the principal hazard appears to be misdiagnosis of gallbladder disease and unnecessary surgery.

Ceftriaxone, 7-[[(2-amino-4-thiazolyl)-2-(Z)-(methyoximino)acetyl]amino]-8- oxo-3-[[(1,2,5,6-tetrahydro-2-methyl-5,6-dioxo-1,2,4-triazin-3-yl)thio]methyl]-5-thia-1- azabicyclo[4.2.0]oct-2-en-2-carboxylic acid (, is synthesized by acylating 7-amino-3-[[(2,5-dihydro-6-hydroxy-2-methyl-1,2,4-triazin-5-on-3-yl)thio]methyl]3-cefem- 4-carboxylic acid (, by the 2-(4-thiazolyl)-2-methoxyiminoacetic acid chloride, which is protected at the amino group by a chloroacetyl group, namely with 2-(2-chloroacetamido-4-thiazolyl)-2-methoxyiminoacetylchloride ( The last is synthesized from ethyl ester of 2-(2-amino-4-thiazolyl)-2-methoxyiminoacetic acid (, the amino group of which is protected by the acylation with chloracetic acid chloride in dimethylacetamide, giving ethyl ester of 2-(2-chloroacetamido-4-thiazolyl)-2-methoxyiminoacetic acid ( Hydrolysis of the ester group of this compound by potassium hydroxide to an acid (, and its subsequent reaction with phosphorous pentachloride in the presence of trimethylamine gives 2-(2-chloroacetamido-4-thiazolyl)-2-methoxyiminoacetylchloride ( The synthesis of 7-amino-3-[[(2,5-dihydro-6-hydroxy-2-methyl-1,2,4-triazin-5- on-3-yl)thio]methyl]-3-cefem-4-carboxylic acid ( is done in parallel.
In order to do this, methylhydrazine is reacted with potassium thiocyanate to give 1-amino-1-methylthiourea (, which is reacted with dimethyloxalate in the presence of sodium methoxide to form a heterocyclization product, 2,5-dihydro-6-hydroxy-2-methyl-3-mercapto-1,2,4-triazin- 5-on ( Reacting this with 7-aminocephalosporanic acid replaces the acetoxy group giving 7-amino-3-[[(2,5-dihydro-6-hydroxy-2-methyl-1,2,4-triazin-5-on-3-yl)thio]methyl]-3- cefem-4-carboxylic acid ( Acylating this with the acid chloride synthesized earlier ( in tetrahydrofuran in the presence of sodium hydroxide gives the desired product ( Removal of the chloroacetyl protection in this molecule is accomplished in the following manner. Subsequent reaction of the product ( with thiourea in the presence of sodium bicarbonate results in the formation of a new thiazole derivative. Subsequent cleaving of the resulting secondary heteroaromatic amine with formic acid gives ceftriaxone (


[Drug interactions]

Potentially hazardous interactions with other drugs
Anticoagulants: effects of coumarins may be enhanced.
Ciclosporin: may cause increased ciclosporin levels.

About 40-65% of a dose of ceftriaxone is excreted unchanged in the urine, principally by glomerular filtration; the remainder is excreted in the bile and is ultimately found in the faeces as unchanged drug and microbiologically inactive compounds.
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