Cefpimizole

Cefpimizole is a peptide.|Cefpimizole is a semisynthetic, broad-spectrum, third-generation cephalosporin with antibacterial activity. Cefpimizole binds to and inactivates penicillin-binding proteins (PBPs) located on the inner membrane of the bacterial cell wall. PBPs are enzymes involved in the terminal stages of assembling the bacterial cell wall and in reshaping the cell wall during growth and division. Inactivation of PBPs interferes with the cross-linkage of peptidoglycan chains necessary for bacterial cell wall strength and rigidity. This results in the weakening of the bacterial cell wall and causes cell lysis.

Imidazole-4, 5-dicarboxylic acid (I) (7.8g, 50mmol) was suspended in 100ml of dry benzene containing 4ml of dimethylformamide, 30ml of thionyl chloride was added, and the mixture was stirred and refluxed at 85°C for 6h. The solvent is evaporated, and 50mi of dry benzene is added to the remainder. Concentrate in vacuo to obtain a solid, add 50 ml of benzene to the solid, and stir at room temperature for 30 min. The insoluble matter was collected by filtration, washed with benzene, and dried to obtain 7.0 g of compound (II) with a yield of 89%. Compound (II) (62.6g, 200mmol) was suspended in 800ml of water and stirred at 40°C for 6h. The insoluble solids were collected by filtration, washed with 100 ml of water, and then washed with acetone (5×100 ml). After vacuum drying, 60.8 g of compound (III) was obtained, the yield was 97%, and the melting point was 284°C (decomposition). Cephaloglycin ((3ephaloglycin) (12.2g, 30mmo1) was suspended in 50ml of water, under ice-cooling, carefully adjusted to Ph=8.5 with 13.5% sodium hydroxide. Under cooling and stirring, add the compound in small amounts in batches (Ⅲ) (9.36g, 30mmo1), and use 13.5% sodium hydroxide solution to maintain the Ph value of the reaction solution at 7.30-7.60. The reaction solution is cooled in an ice bath, stirred for 40 minutes, and adjusted to Ph=6.3 with 6% hydrochloric acid. Stirring: After 10 minutes, the precipitate was removed by filtration, and the filtrate was adjusted to Ph=2 with 6% hydrochloric acid. The resulting solid was collected by filtration, washed with water, and dried under vacuum. The solid was suspended in a mixture of ethyl acetate-methanol (1:1) After stirring for 20 minutes at 40°C, the insoluble matter was removed by filtration. The filtrate was concentrated to about 50ml under reduced pressure. 500nnl ether was added and placed in the refrigerator overnight. The precipitate was collected by filtration, washed with petroleum ether, and dried. 12.5g of compound (IV) was obtained. The yield was 75%. Compound (IV) (7.13g, 12.8mmol) and 4-pyridylethanesulfonic acid (4.9g, 26.3mmol) were suspended in 30ml of water, 2mol/L was added, and sodium hydroxide aqueous solution was added to dissolve it. Adjust to Ph=6.5. Add 87.5g of sodium iodide and stir at 65°C for 70min. Cool, add dropwise to 330ml of acetone under ice-bath cooling and stirring, and then cool overnight. Collect the solid by filtration and dissolve in water , Add acetone to make precipitation again. Use water and ethanol to re-precipitate once according to the previous method. Then dissolve the precipitate in 400ml water at 30℃, adjust to Ph=2 with 6mol/L hydrochloric acid. After stirring for 30min, centrifuge to remove the precipitate. The mother liquor was adjusted to Ph=4 with 2mol/L sodium hydroxide aqueous solution and concentrated to 80ml under vacuum at 30℃. 400ml ethanol was added, and the precipitate was collected by filtration. The precipitate was dissolved in 40ml water and adjusted to Ph=3.3 with 2mol/L hydrochloric acid. Chromatography with 120ml Ambelilite XAD-7, eluting with water. Collect the eluent containing the product and concentrate under reduced pressure. Adjust the concentrate to Ph=3.2 with 2mol/L hydrochloric acid, add 300ml acetone under cooling and stirring. Filter. The precipitate was collected, dried in vacuum, dissolved in water, and freeze-dried to obtain 2.7 g of cefomizole sodium with a yield of 28%.

It is used for acute bronchitis, chronic bronchitis, pneumonia, cholecystitis, cholangitis, peritonitis, sepsis caused by sensitive bacteria such as pneumococcus, digestive streptococcus, Escherichia coli, Pseudomonas aeruginosa, and influenza bacillus.

Molecular Weight:670.7
XLogP3:-0.3
Hydrogen Bond Donor Count:5
Hydrogen Bond Acceptor Count:12
Rotatable Bond Count:11
Exact Mass:670.11518339
Monoisotopic Mass:670.11518339
Topological Polar Surface Area:277
Heavy Atom Count:46
Complexity:1340
Defined Atom Stereocenter Count:3
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes