66-79-5 Usage
Description
Chemically this is 3-methyl-5-phenyl-4-isoxazolyl penicillin. It was
synthesized in 1961 and has been extensively used in North America.
It is available as an oral solution of 120 mg/5 ml. It usually comes in an injectable formulation of 1 and 2 g. A 10-g injectable formulation is also marketed.
Indications
In terms of the spectrum of antimicrobial action, oxacillin is analogous to benzylpenicillin.
However, it combines the resistance to penicillinase with durability in an acidic medium, which
allows it to be used not only intramuscularly, but also orally. It is used for infections caused by penicillinase-producing staphylococci that are resistant to benzyl- and phenoxymethylpenicillins (septicemia, pneumonia, abscesses, empyemia, osteomyelitis, infected burns, infected
wounds, and others). Synonyms of this drug are cryptocillin, liucipen, optocillin, totocillin, and
others.
Definition
ChEBI: A penicillin antibiotic carrying a 5-methyl-3-phenylisoxazole-4-carboxamide group at position 6.
Therapeutic Function
Antibacterial
Antimicrobial activity
There is complete cross-resistance and
tolerance with other group 3 penicillins. Oxacillin is frequently
used to replace methicillin for standardized susceptibility testing
to detect resistant staphylococci.
Acquired resistance
In addition to methicillin-resistant strains producing the low
affinity PBP 2a, rare methicillin-susceptible isolates of Staph.
aureus display reduced susceptibility to oxacillin, due to
incompletely defined chromosomal resistance mechanisms.
Contact allergens
Oxacillin is a semisynthetic penicillin of the group M.
It is closely related to cloxacillin.
Clinical Use
Uses are those of group 3 penicillins
Side effects
There is cross-allergy with other penicillins and reactions are generally typical of the group. Abnormalities of liver function, especially elevation of transaminase levels, may occur, sometimes accompanied by fever, nausea, vomiting and eosinophilia. As with benzylpenicillin, neurotoxicity may develop on high dosage in patients with renal failure. Pseudomembranous colitis has been reported.
Synthesis
Oxacillin, [2S-(2α,5α,6β)]-3,3-dimethyl-7-oxo-6-(5-methyl-3-phenyl-4-isoxazolcarboxamido)-4-thia-1-azabicyclo[3.2.0]-heptan-2-carboxylic acid (32.1.1.10), is synthesized by reacting 5-methyl-3-phenyl-4-isoxazolcarboxylic acid chloride (32.1.1.9) with
6-APA in the presence of sodium bicarbonate. The 5-methyl-3-phenyl-4-isoxazolcarboxylic acid chloride (32.1.1.9) is synthesized by the following scheme.
Reacting benzaldehyde with hydroxylamine gives benzaldoxime (32.1.1.5), which
when oxidized by chlorine gives benzhydroxamic acid chloride (32.1.1.6). This is reacted
with acetoacetic ester in the presence of sodium ethoxide, giving the ethyl ester of
5-methyl-3-phenyl-4-isoxazolcarboxylic acid (32.1.1.7). Alkaline hydrolysis of the resulting ester gives the corresponding acid (32.1.1.8), which is reacted with thionyl chloride to
give the acid chloride necessary for acylation.
Check Digit Verification of cas no
The CAS Registry Mumber 66-79-5 includes 5 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 2 digits, 6 and 6 respectively; the second part has 2 digits, 7 and 9 respectively.
Calculate Digit Verification of CAS Registry Number 66-79:
(4*6)+(3*6)+(2*7)+(1*9)=65
65 % 10 = 5
So 66-79-5 is a valid CAS Registry Number.
InChI:InChI=1/C19H19N3O5S/c1-9-11(12(21-27-9)10-7-5-4-6-8-10)15(23)20-13-16(24)22-14(18(25)26)19(2,3)28-17(13)22/h4-8,13-14,17H,1-3H3,(H,20,23)(H,25,26)/t13-,14+,17-/m1/s1
66-79-5Relevant articles and documents
Synthesis of low-molecular-weight copolymers of N-vinylpyrrolidone with 2-hydroxyethyl methacrylate and of polymeric oxacillin esters derived from them
Solovskii,Korchagin,Tarabukina,Vlasova,Shpyrkov,Amirova
, p. 127 - 132 (2006)
The radical copolymerization of N-vinylpyrrolidone with 2-hydroxyethyl methacrylate in 2-propanol at 60°C, initiated by azobis(isobutyronitrile) and inhibited by mercaptoethanol or terminated after a short period, was studied. The low-molecular-weight copolymers obtained were used to prepare new polymeric forms of Oxacillin antibiotic. The chemical uniformity, composition, and antimicrobial activity of the new derivatives were studied, and the rate of their hydrolysis in saline (pH 7.3) and glycine buffer (pH 2.0) was determined. Pleiades Publishing, Inc., 2006.
Modifications of the C6-substituent of penicillin sulfones with the goal of improving inhibitor recognition and efficacy
Nottingham, Micheal,Bethel, Christopher R.,Pagadala, Sundar Ram Reddy,Harry, Emily,Pinto, Abishai,Lemons, Zachary A.,Drawz, Sarah M.,Akker, Focco Van Den,Carey, Paul R.,Bonomo, Robert A.,Buynak, John D.
scheme or table, p. 387 - 393 (2011/03/17)
In order to evaluate the importance of a hydrogen-bond donating substituent in the design of β-lactamase inhibitors, a series of C6-substituted penicillin sulfones, lacking a C2′ substituent, and having an sp 3 hybridized C6, was prepared and evaluated against a representative classes A and C β-lactamases. It was found that a C6 hydrogen-bond donor is necessary for good inhibitory activity, but that this feature alone is not sufficient in this series of C6β-substituted penicillin sulfones. Other factors which may impact the potency of the inhibitor include the steric bulk of the C6 substituent (e.g., methicillin sulfone) which may hinder recognition in the class A β-lactamases, and also high similarity to the natural substrates (e.g., penicillin G sulfone) which may render the prospective inhibitor a good substrate of both classes of enzyme. The best inhibitors had non-directional hydrogen-bonding substituents, such as hydroxymethyl, which may allow sufficient conformational flexibility of the acyl-enzyme for abstraction of the C6 proton by E166 (class A), thus promoting isomerization to the β-aminoacrylate as a stabilized acyl-enzyme.
LIQUID PHARMACEUTICAL FOR ORAL DELIVERY
-
, (2008/06/13)
A liquid pharmaceutical for oral delivery wherein at the time of use, a solid unit dosage form is added to the liquid wherein the unit dosage form is comprised of a substrate soluble in the liquid and a particulate pharmaceutically active material in a pharmaceutically effective amount. At the time of use, the unit dosage form is added to the liquid, without requiring measurement of the liquid, and the entire liquid is consumed to provide for oral delivery of the pharmaceutically effective amount of material.
