32887-01-7 Usage
Description
Mecillinam, also known as amidinocillin, is a penicillin nucleus (6 APA) derivative that exhibits potent antibacterial activity against a wide range of aerobic and anaerobic Gram-negative bacteria. It is characterized by its effectiveness against E. coli and B. fragilis, while it does not show activity against Staphylococcus aureus, Enterococcus, or Pseudomonas. Mecillinam is also known for its synergistic effects when combined with other beta-lactam drugs, making it a valuable option for treating severe Gram-negative infections. It is a white solid and is commercially available under the brand name Coactin by Roche.
Uses
Used in Pharmaceutical Industry:
Mecillinam is used as an antibiotic for the treatment of infections caused by Gram-negative bacteria. Its application is particularly relevant in cases where there is a need for a targeted approach to combat specific bacterial strains without affecting other beneficial bacteria.
Used in Combination Therapy:
Mecillinam is used as a synergistic agent in combination with other beta-lactam drugs to enhance the treatment of severe Gram-negative infections. This combination approach helps to overcome potential resistance and provides a more effective treatment option.
Used in Research and Development:
Mecillinam serves as a valuable compound in the research and development of new antibiotics and treatment strategies for Gram-negative bacterial infections. Its unique properties and synergistic effects with other drugs make it an important candidate for further study and potential development of novel therapeutic agents.
Originator
Selexidin,Leo,UK,1979
Manufacturing Process
The starting material N-formylhexamethyleneimine was prepared from hexamethyleneimine and chloral.12.7 g of N-formylhexamethyleneimine were dissolved in 250 ml of dry ether.
While stirring and cooling, 8.5 ml of oxalyl chloride in 50 ml of dry ether were
added dropwise, whereafter the mixture was stirred overnight at room
temperature. The precipitated amide chloride was filtered off and washed with
dry ether, and was placed in an exsiccator.A solution of the amide chloride (4.6 g) in dry, alcohol-free chloroform (20 ml)
was added slowly to a solution of trimethylsilyl 6-amino-penicillanate (7.2 g)
and triethylamine (3.5 ml) in dry, alcohol-free chloroform (50 ml) with stirring
and cooling to -70°C. The temperature was raised to 0°C during 1.5 hours.
The solution was evaporated to dryness in vacuo and the residue was
triturated with dry ether (200 ml). The precipitate was filtered off and washed
with dry ether. The filtrate was diluted with ether (200 ml). 2-Butanol (2.8 ml)
was added dropwise with stirring and cooling to 0°C. The stirring was
continued for 1/4 hour at 0°C, whereupon the precipitate was filtered off,
washed with ether and dried. It was a white, amorphous powder, soluble in
water.
Therapeutic Function
Antibacterial
Antimicrobial activity
The antibacterial spectrum differs greatly from that of the
aminopenicillins in that the compound displays high activity
against many Gram-negative bacteria but limited activity
against Gram-positive organisms.
Mecillinam is active against many Enterobacteriaceae due to
its selective binding to PBP 2, although the susceptibility of
Proteus and Providencia spp. is variable. H. influenzae is less susceptible
than enteric bacilli, and Acinetobacter spp., B. fragilis
and Ps. aeruginosa are resistant.
It is readily inactivated by many β-lactamases, although it
is more stable than ampicillin.
Acquired resistance
Intrinsic resistance in susceptible species of enterobacteria
is uncommon and many ampicillin-resistant strains are susceptible.
Bacteria that are resistant to both ampicillin and
mecillinam are usually those producing large amounts of
β-lactamase, most commonly plasmid-mediated enzymes.
Pharmacokinetics
Oral absorption (pivmecillinam): c. 75%
Cmax 200 mg intravenous infusion: 12 mg/L end infusion
200 mg intramuscular: c. 6 mg/L after 45 min
400 mg oral (pivmecillinam): 2–5 mg/L after c. 1 h
Plasma half-life: 50 min
Volume of distribution: 0.2–0.4 L/kg
Plasma protein binding: 5–10%
Absorption
Oral absorption is very poor, with conventional doses producing plasma levels of <1 mg/L and recovery of only about 5% in the urine. A 400 mg dose of the pivaloyl ester is equivalent to 273 mg mecillinam. It is relatively well absorbed and rapidly liberates the parent compound. Metabolism and excretion
The amidino side chain undergoes spontaneous aqueous hydrolysis to the N-formyl derivative, which retains some antibacterial activity. Hydrolysis of the β-lactam ring also occurs.
Approximately 60% is excreted unchanged in the urine in the first 6 h, achieving concentrations exceeding 1 g/L. The concentration in bile can reach 40 or 50 mg/L in patients with normally functioning gallbladders treated with 800 mg intramuscularly.
Clinical Use
Urinary tract infection (pivmecillinam)
Other infections with susceptible Gram-negative bacilli (usually in
combination with other agents)
Side effects
It is generally well tolerated, and serious anaphylactic responses
are said to be rare. Nausea and vomiting, which may be persistent,
occur with diarrhea in some patients treated with
pivmecillinam.
Check Digit Verification of cas no
The CAS Registry Mumber 32887-01-7 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 3,2,8,8 and 7 respectively; the second part has 2 digits, 0 and 1 respectively.
Calculate Digit Verification of CAS Registry Number 32887-01:
(7*3)+(6*2)+(5*8)+(4*8)+(3*7)+(2*0)+(1*1)=127
127 % 10 = 7
So 32887-01-7 is a valid CAS Registry Number.
InChI:InChI=1/C15H23N3O3S/c1-15(2)11(14(20)21)18-12(19)10(13(18)22-15)16-9-17-7-5-3-4-6-8-17/h9-11,13H,3-8H2,1-2H3,(H,20,21)/t10-,11+,13-/m1/s1
32887-01-7Relevant articles and documents
Prodrug derivatives of carboxylic acid drugs
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, (2008/06/13)
Novel ester derivatives of carboxylic acid medicaments of formula (I), wherein R--COO--represents the acyloxy residue of a carboxylic acid drug or medicament, n is an integrer from 1 to 3, and R1 and R2 are the same or different and are selected from a group consisting of an alkyl, an alkenyl, an aryl, an aralkyl, a cycloalkyl and which group may be unsubstituted or substituted, or R1 and R2 together with the N forms a 4-, 5-, 6- or 7-membered heterocyclic ring, which in addition to the nitrogen atom may contain one or two further heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur and which heterocyclic group may be substituted. These compounds are highly biolabile prodrug forms of the corresponding carboxylic acid compounds and are highly susceptible to undergoing enzymatic hydrolysis in vivo whereas they are highly stable in aqueous solution. The novel derivatives are less irritating to mucosa than the parent carboxylic acids and may provide an improved bio-availability of the drugs.
Semisynthetic penicillins. X. Synthesis of 6-formamidinopenicillanic acid derivatives of cyclic secondary amines
Busko-Oszczapowicz,Cieslak
, p. 43 - 48 (2007/10/09)
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