Cefpiramide

ChEBI: A third-generation cephalosporin antibiotic with [(1-methyl-1H-tetrazol-5-yl)sulfanyl]methyl and (R)-2-{[(4-hydroxy-6-methylpyridin-3-yl)carbonyl]amino}-2-(4-hydroxyphenyl)acetamido groups at positions 3 and 7, respectiv ly, of the cephem skeleton. It has a broad spectrum of antibacterial activity.

Solid

Cefpiramide is a third-generation cephalosporin antibiotic with [(1-methyl-1H-tetrazol-5-yl)sulfanyl]methyl and (R)-2-{[(4-hydroxy-6-methylpyridin-3-yl)carbonyl]amino}-2-(4-hydroxyphenyl)acetamido groups at positions 3 and 7, respectively, of the cephem skeleton. It has a broad spectrum of antibacterial activity. It has a role as an antibacterial drug. It is a cephalosporin and a carboxylic acid. It is a conjugate acid of a cefpiramide(1-).|Cefpiramide is a third-generation cephalosporin antibiotic.|Cefpiramide is a third-generation, semi-synthetic, beta-lactam cephalosporin antibiotic with antibacterial activity. Cefpiramide binds to penicillin-binding proteins (PBPs), transpeptidases that are responsible for crosslinking of peptidoglycan. By preventing crosslinking of peptidoglycan, cell wall integrity is lost and cell wall synthesis is halted.

D-(-)-p-Hydroxyphenylglycine (I) (4.175g, 25mmo1) and triethylamine (3.79g, 37.5mmo1) dissolved in 13ml water, add 2-(4-methoxybenzyloxycarbonyl sulfide) )-4, 6-lutidine (II) (8.36g, 27.5mmol) in 17ml dioxane solution. Then it was stirred at room temperature for 2h. Add 33ml of water and extract with 45ml of ethyl acetate to remove unreacted carbonate (II). The water layer was cooled to 0-5°C, adjusted to Ph=2 with 6mol/L and hydrochloric acid, extracted once with 45ml ethyl acetate, and then extracted twice with 20ml ethyl acetate. The extracts were combined, washed twice with 25 ml of 5% hydrochloric acid aqueous solution, and washed with 40 ml of saturated sodium chloride aqueous solution three times, and dried with anhydrous magnesium sulfate. Concentrate to 1/3 of the volume, cool to below 10°C, filter the crystals, wash with 12ml of ethyl acetate, and dry in vacuo to obtain 7.47g of compound (III), yield 90.2%, melting point 136-137°C. Compound (III) (0.2mol) and N-methylmorpholine (0.2mol) were dissolved in 420ml of acetonitrile, and cooled to -20～-15℃ under stirring. Add isobutyl chloroformate (0.2mol), maintain at -20～-15℃ for 10min. Compound (IV) (prepared by reacting 0.42mol of N, O-bis(trimethylsilyl)acetamide and 0.2mol of free amine of compound (IV) in 350ml of acetonitrile) was added and stirred at -15°C for 2h. Slowly rise to 5°C and stir at 5°C for another 1h. 25 ml of methanol was added, and the free amine of the unreacted compound (IV) was removed by filtration. The filtrate was concentrated to dryness in vacuo, and the residue was dissolved in 10% potassium bicarbonate aqueous solution. Wash with ethyl acetate twice, then add fresh ethyl acetate, adjust to Ph=2 with 2mol/L hydrochloric acid at 0-5°C and stirring. The organic layer was separated, and the aqueous layer was extracted twice with ethyl acetate. The organic layers were combined, washed with an aqueous sodium chloride solution, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was treated with dichloromethane. The precipitate was collected by filtration, washed with dichloromethane, and dried in vacuum to obtain compound (V) with a melting point of 127-134°C (decomposition). 10mmol of compound (V) was stirred in 30ml of trifluoroacetic acid in 6ml of anisole at room temperature for 20min. Under stirring, this solution was added to 400 ml of ether. The precipitate was collected by filtration, washed with ether, and dried in vacuum to obtain compound (VI), which was directly used in the next reaction without purification. 30mmol of triethylamine and 10mmol of compound (VII) were dissolved in 30-50ml of dimethylsulfoxide, 10mmol of compound (VI) was added with stirring, and then stirred at room temperature for 30min. Filter to remove traces of insoluble matter, and add the filtrate to 600-1000ml of acetone under stirring. The precipitate was collected by filtration, washed with acetone, and dried in vacuum. Then dissolve it in 40-80ml of water and 40-80ml of methanol (or acetonitrile), and filter to remove any insoluble matter. Adjust to Ph=2 with 2mol/L hydrochloric acid at 5～15℃. The precipitate was collected by filtration, washed with water-methanol (or acetonitrile), and dried under vacuum. Finally, it was purified by preparative liquid chromatography to obtain cefpiramide.

Used for septicemia caused by sensitive bacteria such as Staphylococcus, Peptococcus, Enterobacter, Proteus, Influenza, Streptococcus, etc. Cholangitis, intrauterine infection, etc.

Molecular Weight:612.6
XLogP3:-0.1
Hydrogen Bond Donor Count:5
Hydrogen Bond Acceptor Count:13
Rotatable Bond Count:9
Exact Mass:612.12093748
Monoisotopic Mass:612.12093748
Topological Polar Surface Area:259
Heavy Atom Count:42
Complexity:1270
Defined Atom Stereocenter Count:3
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes