66148-78-5

Basic information

• Product Name: (2S,5R,6S)-6-[(3-Hydroxy-3-oxo-2-thiophen-3-ylpropanoyl)amino]-6-methoxy-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid
• Synonyms: TEMOCILLIN SODIUM;(2S,5R,6S)-6-[(3-Hydroxy-3-oxo-2-thiophen-3-ylpropanoyl)amino]-6-methoxy-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid;N-((2S,5R,6S)-2-Carboxy-6-methoxy-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-6-yl)-3-thiophenemalonamic acid;Temocillin;(6S)-6-[2-Carboxy-2-(3-thienyl)acetamido]-6-methoxypenicillanic acid;BRL-17421;Temopen;(6S)-6-[(Carboxy-3-thienylacetyl)amino]-6-methoxypenicillanic acid
• CAS NO: 66148-78-5
• Molecular Formula: C₁₆H₁₈N₂O₇S₂
• Molecular Weight: 458.42
• EINECS: 266-184-1
• Mol File: 66148-78-5.mol
• Article Data: 1

Chemical Properties

• Boiling Point: 761.9 °C at 760 mmHg
• Flash Point: 414.6 °C
• Appearance: /
• Density: 1.6 g/cm³
• Vapor Pressure: 2.09E-24mmHg at 25°C
• Refractive Index: 1.675
• PKA: 2.46±0.50(Predicted)
• CAS DataBase Reference: (2S,5R,6S)-6-[(3-Hydroxy-3-oxo-2-thiophen-3-ylpropanoyl)amino]-6-methoxy-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid(CAS DataBase Reference)
• NIST Chemistry Reference: (2S,5R,6S)-6-[(3-Hydroxy-3-oxo-2-thiophen-3-ylpropanoyl)amino]-6-methoxy-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid(66148-78-5)
• EPA Substance Registry System: (2S,5R,6S)-6-[(3-Hydroxy-3-oxo-2-thiophen-3-ylpropanoyl)amino]-6-methoxy-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid(66148-78-5)

Safety Data

• Hazardous Substances Data: 66148-78-5(Hazardous Substances Data)

Usage

Uses

Antibacterial.

Antimicrobial activity

The introduction of the 6-α-methoxy group has resulted in loss of activity against Gram-positive cocci and anaerobic Gram-negative bacilli, but it is active against enterobacteria (MIC 1–8 mg/L), H. influenzae and Mor. catarrhalis, with somewhat elevated MICs against carbapenemase- producing isolates of K. pneumoniae (MIC 16–64 mg/L) and Esch. coli (modal MICs 8–16 mg/L). In most cases, β-lactamase-positive and negative strains are equally susceptible. In contrast to the structurally related ticarcillin, it is inactive against Ps. aeruginosa, but Burkholderia cepacia, Ps. acidovorans and Aeromonas spp. are susceptible (MIC 4 mg/L). Most Acinetobacter spp. are resistant, and Ser. marcescens exhibits variable susceptibility. It is bactericidal at concentrations 2–4 times the MIC; filaments formed at lower concentrations slowly lyse at higher drug levels. Temocillin consists of diastereoisomers. The naturally predominant R epimer is more rapidly bactericidal than the S epimer. It is highly resistant to most bacterial β-lactamases, including those that confer resistance to extended-spectrum cephalosporins. It is hydrolyzed by β-lactamases produced by Flavobacterium spp. and by those of Bacteroides spp.

Pharmacokinetics

Oral absorption: Negligible Cmax 1 g intramuscular injection: 70 mg/L 1 g rapid intravenous infusion: 172 mg/L after 5 min Plasma half-life: 4.3–5.4 h Plasma protein binding: 85% Absorption and distribution It is not absorbed when given orally and must be administered parenterally. Relatively high protein binding, together with its distribution in a volume less than the extracellular fluid, accounts for its relatively low renal clearance and subsequent high urinary concentrations that may be effective against some Enterobacteriaceae resistant to other β-lactam antibiotics. In artificial blister fluid and peritoneal fluid, concentrations reach 50% of the peak plasma level; in lymph, concentrations reach 25–60% of the simultaneous plasma level, with a similar half-life. The R epimer differs from the S epimer in lower protein binding, a 25% greater volume of distribution and a 60% shorter half-life. Metabolism and excretion Elimination is principally in the glomerular filtrate, with 80% of the dose appearing in the urine in the first 24 h. A small amount is disposed of in the bile and by degradation. Elimination declines in parallel with renal function, the half-life reaching 30 h in patients with creatinine clearance below 5%.

Clinical Use

Severe infection with susceptible bacteria, including urinary and respiratory tract infections, peritonitis and septicemia.

Side effects

As with all penicillins, hypersensitivity reactions, including serious anaphylactic responses, may occur. It is generally well tolerated and administration of 4 g intravenously every 12 h produced no significant effect on template bleeding time, prothrombin time or ADP-induced platelet aggregation.

Drug interactions

Potentially hazardous interactions with other drugs Temocillin can reduce the excretion of methotrexate (increased risk of toxicity).

Metabolism

Temocillin is excreted unchanged mainly in the kidney.

InChI:InChI=1/C16H18N2O7S2/c1-15(2)9(12(22)23)18-13(24)16(25-3,14(18)27-15)17-10(19)8(11(20)21)7-4-5-26-6-7/h4-6,8-9,14H,1-3H3,(H,17,19)(H,20,21)(H,22,23)/t8?,9-,14+,16-/m0/s1

Upstream product

• 61545-07-1 rac-6β-((Ξ)-2-benzyloxycarbonyl-2-thiophen-3-yl-acetylamino)-6α-methoxy-penicillanic acid benzyl ester 
• 35353-32-3 6β-amino-6α-methoxy-penicillanic acid benzyl ester 
• 50893-38-4 monobenzyl 3-thienylmalonic acid chloride 

Relevant articles and documents

Process for the preparatin of β-lactam compounds

The present invention provides a process for the substitution of an acylamino β-lactam compound at the carbon atom carrying the acylamino group, which process comprises reacting the β-lactam compound with an halogenating agent and a nucleophilic reagent; characterized in that the acylamino group has an acidic group on the carbon atom adjacent the carbonyl group. In particular the process of this invention comprises reacting a β-lactam of partial structure (I): STR1 where X represents an acidic group; with an halogenating agent and a nucleophilic reagent.