2-Oxazolidone is a

heterocyclic A heterocyclic compound or ring structure is a cyclic compound that has atoms of at least two different elements as members of its ring(s). Heterocyclic chemistry is the branch of organic chemistry dealing with the synthesis, properties, and ...

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. The ...

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 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 ca ...

, which are used for

chiral synthesis Enantioselective synthesis, also called asymmetric synthesis, is a form of chemical synthesis. It is defined by IUPAC as "a chemical reaction (or reaction sequence) in which one or more new elements of chirality are formed in a substrate molecul ...

. Usually, the

acid chloride In organic chemistry, an acyl chloride (or acid chloride) is an organic compound with the functional group . Their formula is usually written , where R is a side chain. They are reactive derivatives of carboxylic acids (). A specific example o ...

substrate reacts with the oxazolidinone to form an imide. 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 inhibitor A protein synthesis inhibitor is a compound that stops or slows the growth or proliferation of cells by disrupting the processes that lead directly to the generation of new proteins. While a broad interpretation of this definition could be used t ...

s, 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, v ...

(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%. Ho ...

. *

Posizolid Posizolid is an oxazolidinone antibiotic under investigation by AstraZeneca for the treatment of bacterial infections. At a concentration of 2 mg/L it inhibited 98% of all Gram-positive bacteria tested in vitro ''In vitro'' (meaning ...

, which appears to have excellent, targeted bactericidal activity against all common gram-positive bacteria, regardless of resistance to other classes of antibiotics. *

Tedizolid Tedizolid (formerly torezolid, trade name Sivextro), is an oxazolidinone-class antibiotic. Tedizolid phosphate is a phosphate ester prodrug of the active compound tedizolid. It was developed by Cubist Pharmaceuticals, following acquisition of ...

, (Sivextro) which is approved for acute skin infections *

Radezolid Radezolid (INN, codenamed RX-1741) is a novel oxazolidinone 2-Oxazolidone is a heterocyclic organic compound containing both nitrogen and oxygen in a 5-membered ring. Oxazolidinones Evans auxiliaries Oxazolidinones are a class of compounds con ...

(RX-1741) has completed some phase-II clinical trials. *

Cycloserine Cycloserine, sold under the brand name Seromycin, is a GABA transaminase inhibitor and an antibiotic, used to treat tuberculosis. Specifically it is used, along with other antituberculosis medications, for active drug resistant tuberculosis. It ...

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 ...

. 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 Rivaroxaban, sold under the brand name Xarelto among others, is an anticoagulant medication (blood thinner) used to treat and prevent blood clots. Specifically it is used to treat deep vein thrombosis and pulmonary emboli and prevent blood clo ...

, which is approved by the FDA for venous thromboembolism prophylaxis.

History

The first ever used oxazolidinone was

cycloserine Cycloserine, sold under the brand name Seromycin, is a GABA transaminase inhibitor and an antibiotic, used to treat tuberculosis. Specifically it is used, along with other antituberculosis medications, for active drug resistant tuberculosis. It ...

(''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 infections, ...

(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, v ...

, discovered and developed by

Pharmacia & Upjohn Pharmacia & Upjohn was a global pharmaceutical company formed by the merger of Sweden-based Pharmacia AB and the American company Upjohn in 1995. Today the remainder of the company is owned by Pfizer. In 1997, Pharmacia & Upjohn sold several bra ...

. 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 includin ...

began investigating

posizolid Posizolid is an oxazolidinone antibiotic under investigation by AstraZeneca for the treatment of bacterial infections. At a concentration of 2 mg/L it inhibited 98% of all Gram-positive bacteria tested in vitro ''In vitro'' (meaning ...

, which is in clinical trials for use in humans.

References

External links