61477-96-1

Basic information

• Product Name: Pipracil
• Synonyms: PIPERACILLIN NA;PIPERACILLIN SODIUM;3-dioxo-1-piperazinyl)carbonyl)amino)phenylacetyl)amino)-7-oxo-l-(2s-(2-al;4-thia-1-azabicyclo(3.2.0)heptane-2-carboxylicacid,3,3-dimethyl-6-(((((4-ethy;6-(d-(-)-alpha-(4-ethyl-2,3-dioxo-1-piperazinecarboxamido)phenylacetamido)pe;[2S-[2alpha,5alpha,6beta(S*)]]-6-[[[[(4-ethyl-2,3-dioxopiperazin-1-yl)carbonyl]amino]phenylacetyl]amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid;PIPERACILLIN EPP(CRM STANDARD);PIPERACILLIN USP(CRM STANDARD)
• CAS NO: 61477-96-1
• Molecular Formula: C₂₃H₂₇N₅O₇S
• Molecular Weight: 517.55
• EINECS: 262-811-8
• Product Categories: Antibiotic Explorer;Aromatics;Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals;Sulfur & Selenium Compounds
• Mol File: 61477-96-1.mol
• Article Data: 8

Chemical Properties

• Melting Point: 183-185?C (dec.)
• Appearance: Crystalline solid
• Density: 1.51 g/cm³
• Vapor Pressure: 0Pa at 20℃
• Storage Temp.: Hygroscopic, -20°C Freezer, Under Inert Atmosphere
• Solubility: Freely soluble in methanol. Only sparingly soluble in aqueous so
• PKA: 2.44±0.50(Predicted)
• Water Solubility: 256.8mg/L at 20℃
• Stability: Hygroscopic
• CAS DataBase Reference: Pipracil(CAS DataBase Reference)
• NIST Chemistry Reference: Pipracil(61477-96-1)
• EPA Substance Registry System: Pipracil(61477-96-1)

Safety Data

• Hazard Codes: Xi
• Statements: 42/43
• Safety Statements: 36/37
• RTECS: XH8952200
• Hazardous Substances Data: 61477-96-1(Hazardous Substances Data)

Usage

Chemical Properties

White Crystalline Solid; odorless; slightly hygroscopic. It is easily soluble in methanol, soluble in absolute ethanol or acetone, and very slightly soluble in water. It is a semi-synthetic penicillin antibiotic with broad-spectrum antibacterial effect.

Originator

Pentcillin, Toyama ,Japan ,1980

Uses

Piperacillin is a semisynthetic penicillin with wide spectrum of antimicrobial activity, particularly pseudomonas strains. It is used to treat moderate-to-severe infections due to susceptible organisms.

Definition

ChEBI: Piperacillin is a penicillin in which the substituent at position 6 of the penam ring is a 2-[(4-ethyl-2,3-dioxopiperazin-1-yl)carboxamido]-2-phenylacetamido group. It has a role as an antibacterial drug. It is a penicillin and a penicillin allergen. It is a conjugate acid of a piperacillin(1-).

Therapeutic Function

Antibiotic

Antimicrobial activity

It displays good activity against non-β-lactamaseproducing strains of N. gonorrhoeae, ampicillin-susceptible H. influenzae and many Enterobacteriaceae. It is the most active of the antipseudomonal penicillins against Ps. aeruginosa and retains its activity in the absence of a β-lactamase inhibitor. Synergy with aminoglycosides has been demonstrated against many strains of Enterobacteriaceae and Ps. aeruginosa.

Acquired resistance

There is complete cross-resistance with other ureidopenicillins, but ticarcillin-resistant strains of Ps. aeruginosa may be susceptible. Piperacillin-resistant strains of B. fragilis and other Bacteroides spp. are common. Because piperacillin is hydrolyzed by most β-lactamases, many β-lactamaseproducing isolates are resistant unless it is protected by β-lactamase inhibitors.

Pharmacokinetics

Oral absorption: Negligible Cmax 2 g (2–3 min intravenous injection): 305 mg/L after 5 min Plasma half-life: 0.9 h Volume of distribution: 16–24 L/1.73 m2 Plasma protein binding: 16% In patients with meningitis, mean CSF penetration of 30% has been found. The urine is the principal route of excretion, 50–70% of the dose appearing over 12 h, most in the first 4 h. Most is excreted via the tubules, 75–90% in active form. The half-life is prolonged in renal failure but much less than is the case with carboxypenicillins. There is substantial biliary excretion, levels in the common duct bile after a 1 g intravenous dose commonly reaching 500 mg/L or more. During hemodialysis the plasma half-life remains elevated and only 10–15% of the dose is removed.

Clinical Use

Piperacillin (Pipracil) is the most generally useful of the extended-spectrum acylureidopenicillins. It is more active thanmezlocillin against susceptible strains of Gram-negativeaerobic bacilli, such as Serratia marcescens, Proteus,Enterobacter, Citrobacter spp., and P. aeruginosa.Mezlocillin, however, appears to be more active againstProvidencia spp. and K. pneumoniae. Piperacillin is alsoactive against anaerobic bacteria, especially B. fragilis andS. faecalis (enterococcus). β-Lactamase–producing strainsof these organisms are, however, resistant to piperacillin,which is hydrolyzed by S. aureus β-lactamase. The β-lactamase susceptibility of piperacillin is not absolute becauseβ-lactamase–producing, ampicillin-resistant strainsof N. gonorrhoeae and H. influenzae are susceptible topiperacillin.Piperacillin is destroyed rapidly by stomach acid; therefore,it is active only by intramuscular or intravenousadministration. The injectable form is provided as the white,crystalline, water-soluble sodium salt. Its pharmacokineticproperties are very similar to those of the other acylureidopenicillins.

Side effects

Piperacillin is generally well tolerated, with mild to moderate pain on injection, thrombophlebitis and diarrhea in some patients. It otherwise exhibits side effects common to the group, including hypersensitivity, leukopenia and abnormalities of platelet aggregation without coagulation defect, except on prolonged treatment.

Synthesis

Piperacillin, (2S,5R,6R)-3,3-dimethyl-7-oxo-6-[(2R)-2-[(4-ethyl-2,3-dioxo- 1-piperazinyl)formamido]-2-phenylacetamido]-4-thia-1-azabicyclo[3.2.0]-heptan-2-carboxylic acid (32.1.1.30), is also synthesized by acylating ampicillin (32.1.1.16), but with 1-chlorocarbonyl-4-ethylpiperazin-2,3-dione (32.1.1.29). The necessary 1-chlorocarbonyl-4- ethylpiperazin-2,3-dione (32.1.1.29) is synthesized by reacting N-ethylethylenediamine with diethyloxalate, forming 4-ethylpiperazin-2,3-dione (32.1.1.28), and then acylating this with phosgene after initial silylation of the product at the nitrogen atom with trimethylchlorosilane.

Mode of action

Piperacillin binds to penicillin binding proteins (PBP) located on the inner membrane of the bacterial cell wall, thereby interfering with the cross-linking of peptidoglycan chains necessary for bacterial cell wall strength and rigidity. As a result, cell wall synthesis is interrupted leading to a weakened cell wall and eventually cell lysis.

InChI:InChI=1/C23H27N5O7S/c1-4-26-10-11-27(19(32)18(26)31)22(35)25-13(12-8-6-5-7-9-12)16(29)24-14-17(30)28-15(21(33)34)23(2,3)36-20(14)28/h5-9,13-15,20H,4,10-11H2,1-3H3,(H,24,29)(H,25,35)(H,33,34)/t13-,14-,15+,20-/m1/s1

Upstream product

• 59702-31-7 1-ethyl-2,3-dioxo-piperazine 
• 69-53-4 ampicillin 
• 59703-00-3 4-ethyl-2,3-dioxopiperazine-1-carbonyl chloride 
• 59703-84-3 sodium piperacillin 

Downstream Products

• 59703-84-3 sodium piperacillin 
• 89785-84-2 tazobactam sodium 

Relevant articles and documents

Preparation method of piperacillin

The invention discloses a preparation method of piperacillin. According to the method, DBU with stronger alkalinity is used as an initiator to promote the reaction of N-ethyl-2, 3-dioxopiperazine andtriphosgene to obtain N-ethyl-2, 3-dioxopiperazine acyl chloride, so that the use of trimethylchlorosilane is avoided; In the condensation reaction, sodium acetate is used as an acid-binding agent, sothat the pollution of carbon dioxide to the environment is avoided. The alkalinity of sodium acetate is weaker than that of sodium bicarbonate, the hydrolysis degree in the reaction process is low, meanwhile, DBU is used as a catalyst, and the N-ethyl-2, 3-dioxopiperazine acyl chloride hydrolysate can also react with ampicillin to obtain piperacillin, so that the reaction yield is increased, andthe production cost is further reduced.

Piperacillin sodium compound containing half water

The invention discloses a piperacillin sodium compound containing half water and a preparation method thereof. Each mole of piperacillin sodium contains a half mole of water. First, ampicillin trihydrate is reacted with 4-ethyl-2,3-dioxypiperazine formyl chloride to form piperacillin acid, then piperacillin acid is reacted with sodium acetate in a mixed solution of acetone and water, isopropanol is added dropwise, and crystallization, filtration and drying are conducted to obtain the piperacillin sodium compound containing half water. The piperacillin sodium compound containing half water hashigh fluidity, low hygroscopicity and impurity content, high thermodynamic stability and a wider application prospect.

In vitro and in vivo evaluation of positively charged liposaccharide derivatives as oral absorption enhancers for the delivery of anionic drugs

Oral delivery of hydrophilic, ionisable drugs remains a major challenge in drug development and a number of active pharmaceuticals fail to reach the market of oral drugs because of a lack of absorption and/or stability issues. One possible approach to improving the bioavailability of such drug candidates is to increase their lipophilicity, which is a key parameter in the permeation across cell membranes. However, modifying the chemical structure by adding lipid residues often results in changes in activity. With ionised molecules, ion-pairing can be considered to associate charged lipid moieties with the parent drug without altering its structure and therefore activity. This study presents the results of in vitro and in vivo evaluation of a series of synthetic, positively charged liposaccharide derivatives combined with an anionic model drug, piperacillin. The antimicrobial activity, plasma stability, Caco-2 cell permeability and oral absorption of the conjugates were assessed. Increases in apparent permeability were observed in vitro for three of the tested formulations, while retaining the antibacterial activity of the drug. However, the in vivo intestinal absorption of piperacillin formulated with the liposaccharide derivatives was found unchanged, possibly due to molecular dissociation, early degradation or structural differences between the intestinal epithelium and cultured monolayers.