2-Oxazolidone is a heterocyclic

organic compound In chemistry, organic compounds are generally any chemical compounds that contain carbon- hydrogen or carbon-carbon bonds. Due to carbon's ability to catenate (form chains with other carbon atoms), millions of organic compounds are known. Th ...

containing both nitrogen and oxygen in a 5-membered ring.

Oxazolidinones

Evans auxiliaries

Oxazolidinones are a class of compounds containing 2-oxazolidone in the structure. In chemistry, they are useful as Evans auxiliaries, which are used for chiral synthesis. Usually, the acid chloride substrate reacts with the oxazolidinone to form an

imide In organic chemistry, an imide is a functional group consisting of two acyl groups bound to nitrogen. The compounds are structurally related to acid anhydrides, although imides are more resistant to hydrolysis. In terms of commercial applicati ...

. Substituents at the 4 and 5 position of the oxazolidinone direct any

aldol reaction The aldol reaction is a means of forming carbon–carbon bonds in organic chemistry. Discovered independently by the Russian chemist Alexander Borodin in 1869 and by the French chemist Charles-Adolphe Wurtz in 1872, the reaction combines two c ...

to the alpha position of the carbonyl of the substrate.

Pharmaceuticals

Oxazolidinones are mainly used as antimicrobials. The antibacterial effect of oxazolidinones is by working as protein synthesis inhibitors, targeting an early step involving the binding of N-formylmethionyl-tRNA to the ribosome. (See Linezolid#Pharmacodynamics) Some of the most important oxazolidinones are antibiotics. Examples of antibiotic oxazolidinones include: *

Linezolid Linezolid is an antibiotic used for the treatment of infections caused by Gram-positive bacteria that are resistant to other antibiotics. Linezolid is active against most Gram-positive bacteria that cause disease, including streptococci, vanco ...

(Zyvox), which is available for intravenous administration and also has the advantage of having excellent oral

bioavailability In pharmacology, bioavailability is a subcategory of absorption and is the fraction (%) of an administered drug that reaches the systemic circulation. By definition, when a medication is administered intravenously, its bioavailability is 100%. ...

. * Posizolid, which appears to have excellent, targeted bactericidal activity against all common gram-positive bacteria, regardless of resistance to other classes of antibiotics. * Tedizolid, (Sivextro) which is approved for acute skin infections * Radezolid (RX-1741) has completed some phase-II clinical trials. * Cycloserine is a second line drug against

tuberculosis Tuberculosis (TB) is an infectious disease usually caused by ''Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it can also affect other parts of the body. Most infections show no symptoms, in w ...

. Note that cycloserine, while technically an oxazolidone, has a different mechanism of action and substantially different properties from the aforementioned compounds. * Contezolid (S)-5-((isoxazol-3-ylamino)methyl)-3-(2,3,5-trifluoro-4-(4-oxo-3,4-dihydropyridin-1(2H)-yl)phenyl)oxazolidin-2-one ( MRX-I) has reported phase 1 data and completed phase II trials in 2015, and is starting a phase 3 trial in 2016. An oxazolidinone derivative used for other purposes is rivaroxaban, which is approved by the FDA for venous thromboembolism prophylaxis.

History

The first ever used oxazolidinone was cycloserine (''4-amino-1,2-oxazolidin-3-one''), a second line drug against tuberculosis since 1956.A. W. Frahm, H. H. J. Hager, F. v. Bruchhausen, M. Albinus, H. Hager: ''Hagers Handbuch der pharmazeutischen Praxis: Folgeband 4: Stoffe A-K.'', Birkhäuser, 1999, Developed during the nineties when several bacterial strains were becoming resistant against such antibiotics as

vancomycin Vancomycin is a glycopeptide antibiotic medication used to treat a number of bacterial infections. It is recommended intravenously as a treatment for complicated skin infections, bloodstream infections, endocarditis, bone and joint infection ...

(Zyvox) is the first approved agent in the class (FDA approval April 2000). The first commercially available 1,3-oxazolidinone antibiotic was

linezolid Linezolid is an antibiotic used for the treatment of infections caused by Gram-positive bacteria that are resistant to other antibiotics. Linezolid is active against most Gram-positive bacteria that cause disease, including streptococci, vanco ...

, discovered and developed by Pharmacia & Upjohn. In 2002

AstraZeneca AstraZeneca plc () is a British-Swedish multinational pharmaceutical and biotechnology company with its headquarters at the Cambridge Biomedical Campus in Cambridge, England. It has a portfolio of products for major diseases in areas includ ...

began investigating posizolid, which is in clinical trials for use in humans.

References

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