CeftazidiMe

Ceftazidime(GR20263) is an antibiotic useful for the treatment of a number of bacterial infections.Target: AntibacterialCeftazidime is an antibiotic useful for the treatment of a number of bacterial infections. It is a third-generation cephalosporin. As with all antibiotics, ceftazidime is not used to treat viral infections. Cephalosporins have activity against Gram-positive and Gram-negative bacteria. The balance of activity tips toward Gram-positive organisms for earlier generations; l

Semisynthetic, broad-spectrum antibacterial derived from CEPHALORIDINE and used especially for Pseudomonas and other gram-negative infections in debilitated patients.

In ceftazidime the oxime moiety is more complex, containing two methyl groups and a carboxylic acid. This assemblage conveys even more pronounced β-lactamase stability, greater anti–Pseudomonas aerugi nosa, and increased activity against Gram-positive organisms. The C-3 side chain has been replaced by a charged pyridinium moiety. The latter considerably enhances water solubility and also highly activates the β-lactam bond toward cleavage. The drug must be protected against heat and light and may darken without significant loss of potency. It is not stable under some conditions. such as the presence of aminoglycosides and vancomycin. It also is attacked readily in sodium bicarbonate solutions. Resistance is mediated by chromosomally mediated β-lactamases and by lack of penetration into target bacteria. Otherwise, it has a very broad antibacterial spectrum.

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ChEBI: A cephalosporin bearing pyridinium-1-ylmethyl and {[(2Z)-2-(2-amino-1,3-thiazol-4-yl)-2-{[(2-carboxypropan-2-yl)oxy]imino}acetamido groups at positions 3 and 7, respectively, of the cephem skeleton.

Method 1: 572 mg (Z)-2-(2-tert-butoxycarbonylpropan-2-oxyimino)-2-(2-tritylaminothiazol-4-yl)acetic acid and 328 mg 3-acetyl Oxymethyl-7-aminocephem-3-ene-4-carboxylic acid tert-butyl ester was dissolved in 10ml of dimethylformamide, cooled to 0°C, and 150mg 1-hydroxybenzotriazole and 225mg DCC were added in sequence. Dicyclohexylcarbodiimide). Heated to room temperature, and stirred at room temperature for 5h and left overnight. Filter and wash the white filter cake with a small amount of ether. The washing liquid and the filtrate were combined, diluted with 50 ml of water, and extracted with ethyl acetate. The extract was washed successively with water, 2 mol/L hydrochloric acid, water, sodium bicarbonate solution and saturated brine, dried, and concentrated. The residue was subjected to column chromatography (silica gel-ether). Collect 3-acetoxymethyl-7-[(Z)-2-(2-tert-butoxycarbonylprop-2-oxyimino)-2-(2-tritylaminothiazole-4- ) Acetamido] cephalosporin-3-ene-4-carboxylic acid tert-butyl effluent, concentrated to give 533mg of product. Part of the product can be recrystallized with diisopropyl ether, melting point 103 ~ 113 ℃ (decomposition), [α] D20 + 8.5 ° (C = 1.0, dimethyl sulfoxide). 2.4g of the product obtained above was dissolved in 18ml of anisole, 18ml of trifluoroacetic acid was added at 0°C, then stirred at room temperature for 2h, and concentrated. The residue was dissolved in ethyl acetate and extracted with saturated sodium bicarbonate solution. The pH value of the extract was adjusted to 6, then ethyl acetate was added, and the aqueous layer was acidified to a pH value of 1.5, saturated with sodium chloride, and then extracted with ethyl acetate. The extracts were combined, washed with saturated brine, dried and concentrated. The residue was dissolved in 20ml of hot 50% formic acid aqueous solution and allowed to stand for 2h. Dilute with 50ml water and filter. The filtrate was concentrated and the residue was redissolved in 50 ml of water and filtered. Freeze under reduced pressure to obtain 920 mg of 3-acetoxymethyl-7-[(Z)-2-(2aminothiazol-4-yl)-2-(2-carboxyprop-2-oxyimino)acetamido ] Cephalosporin-3-ene-4-carboxylic acid, [α]D20+20.0° (C=1.0, dimethyl sulfoxide). 1.8g of the product obtained above and 2ml of pyridine were added to a solution of 7.12g of sodium iodide dissolved in 2.2ml of water under stirring at 80°C. React for 1 h at 80°C, cool and use. Dilute with 100ml water. The pH of the reaction was adjusted to 6.0 with 2 mol/L sodium hydroxide, and concentrated to remove pyridine. The remaining aqueous solution was diluted with 100ml of water, and added two drops of methyl isobutyl ketone, and then with 2mol/k. Acidified by hydrochloric acid to pH=1. Filter and wash the filter cake with 1L of water. The filtrate and washing liquid were combined, washed with ethyl acetate, and then adjusted to pH=6.0 with 2mol/L sodium hydroxide. After concentration to 50 ml, column chromatography was performed with 500 g of Amberlite: XAD-2 resin, using water and then 20% ethanol in water as a developing solution. The effluent containing ceftazidime was collected, concentrated, and frozen under reduced pressure to obtain 0.56 g of product. Method 2: The side chain (I) reacts with phosphorus pentachloride to form the corresponding acid chloride (Ⅱ), without separation, it is directly acylated with 7-aminocephalosporin tert-butyl ester (Ⅲ) to produce the cephalosporin compound (Ⅳ) . It is then treated with a mixture of formic acid and hydrochloric acid to remove all three protecting groups to obtain the cephalosporin compound (V). In the presence of sodium iodide, it reacts with pyridine to replace acetoxy, and then purified to obtain an amorphous solid ceftazidime. Method 3: It is best to use ceftazidime as the raw material, because ceftazidime has 3-pyridylmethyl. After silylation with trimethylsilyl chloride, and then reacting with phosphorus pentachloride at a low temperature, lower alcohol or diol is added to obtain an amorphous solid, and then a suitable solvent such as acetonitrile or isopropanol containing hydrochloric acid is used to After treatment, pure crystalline compound (VI) is obtained. Next, it reacts with the dichloromethane solution of compound (II). After washing the reaction solution with water and distilling off the dichloromethane, dimethylformamide is added to obtain a pure compound (Ⅶ) containing 2.5 molecules of dimethylformamide. No impurities. To the dimethylformamide solution of compound (VII), add a mixture of formic acid and hydrochloric acid for treatment, filter to remove the precipitate, and then add acetone or methanol to obtain a very pure compound (VIII). The compound (Ⅷ) is dissolved in water, the pH value is adjusted to the isoelectric point, and the precipitated ceftazidime pentahydrate crystallizes with high yield and the product is pure and stable. The side chain compound (I) used can be synthesized by the following method.

Third generation cephalosporin antibiotic. Antibacterial

5-HT agonist, anti-migrane

pyrimidine synthesis inhibitor disease-modifying antirheumatic drug

Like most of the third-generation cephalosporin antibiotics described above, ceftazidime has a broad spectrum of antimicrobial action, including the most clinically important microorganisms: Gram-positive, Gram-negative, aerobic, and anaerobic. It is resistant to most beta-lactamases of Gram-positive and Gram-negative bacteria. It is used for treating most serious bacterial infections. Synonyms of this drug are fortum, ceftim, stacef, and tazicef.