2-Oxazolidone
Encyclopedia
2-Oxazolidone is a heterocyclic
organic compound
containing both nitrogen and oxygen in a 5-membered ring.
. Usually, the acid chloride substrate reacts with the oxazolidinone to form an imide
. Substituents at the 4 and 5 position of the oxazolidinone direct any aldol reaction
to the alpha position of the carbonyl of the substrate.
s, targeting an early step involving the binding of N-formylmethionyl-tRNA to the ribosome. Some of the most important oxazolidinones are the last generation of antibiotics used against gram-positive pathogens, including superbugs such as Methicillin-resistant Staphylococcus aureus
. These antibiotics are considered as a choice of last resort where every other antibiotic therapy has failed.
Examples of antibiotic oxazolidinones include:
An oxazolidinone derivative used for other purposes is rivaroxaban
, which is approvedby the FDA for venous thromboembolism prophylaxis.
The first ever used oxazolidinone was Cycloserine
(4-amino-1,2-oxazolidin-3-one), a second line drug against Tuberculosis
since 1956. Developed during the nineties when several bacterial strains were becoming resistant against such antibiotics as vancomycin
. Linezolid
(Zyvox) is the first approved agent in the class.
The first commercially available 1,3-oxazolidinone antibiotic was Linezolid
, discovered and developed by Pharmacia & Upjohn.
In 2002 AstraZeneca
introduced posizolid
(AZD2563).
Heterocyclic compound
A heterocyclic compound is a cyclic compound which has atoms of at least two different elements as members of its ring. The counterparts of heterocyclic compounds are homocyclic compounds, the rings of which are made of a single element....
organic compound
Organic compound
An organic compound is any member of a large class of gaseous, liquid, or solid chemical compounds whose molecules contain carbon. For historical reasons discussed below, a few types of carbon-containing compounds such as carbides, carbonates, simple oxides of carbon, and cyanides, as well as the...
containing both nitrogen and oxygen in a 5-membered ring.
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 synthesisChiral synthesis
Enantioselective synthesis, also called chiral synthesis, asymmetric synthesis or stereoselective synthesis, is organic synthesis that introduces one or more new and desired elements of chirality...
. Usually, the acid chloride substrate reacts with the oxazolidinone to form an imide
Imide
In organic chemistry, an imide is a functional group consisting of two carbonyl groups bound to nitrogen. These compounds are structurally related to acid anhydrides. The relationship between esters and amides and between imides and anhydrides is analogous, the amine-derived groups are less reactive...
. Substituents at the 4 and 5 position of the oxazolidinone direct any aldol reaction
Aldol reaction
The aldol reaction is a powerful means of forming carbon–carbon bonds in organic chemistry.Discovered independently by Charles-Adolphe Wurtz and Alexander Porfyrevich Borodin in 1872, the reaction combines two carbonyl compounds to form a new β-hydroxy carbonyl compound...
to the alpha position of the carbonyl of the substrate.
Pharmaceuticals
Oxazolidinones are mainly used as antibiotics. The antibacterial effect of oxazolidinones is by working as protein synthesis inhibitorProtein synthesis inhibitor
A protein synthesis inhibitor is a substance that stops or slows the growth or proliferation of cells by disrupting the processes that lead directly to the generation of new proteins....
s, targeting an early step involving the binding of N-formylmethionyl-tRNA to the ribosome. Some of the most important oxazolidinones are the last generation of antibiotics used against gram-positive pathogens, including superbugs such as Methicillin-resistant Staphylococcus aureus
Methicillin-resistant Staphylococcus aureus
Methicillin-resistant Staphylococcus aureus is a bacterium responsible for several difficult-to-treat infections in humans. It is also called multidrug-resistant Staphylococcus aureus and oxacillin-resistant Staphylococcus aureus...
. These antibiotics are considered as a choice of last resort where every other antibiotic therapy has failed.
Examples of antibiotic oxazolidinones include:
- LinezolidLinezolidLinezolid is a synthetic antibiotic used for the treatment of serious infections caused by Gram-positive bacteria that are resistant to several other antibiotics...
(Zyvox), which is available for intravenous administration and also has the advantage of having excellent oral bioavailabilityBioavailabilityIn pharmacology, bioavailability is a subcategory of absorption and is used to describe the fraction of an administered dose of unchanged drug that reaches the systemic circulation, one of the principal pharmacokinetic properties of drugs. By definition, when a medication is administered...
. - PosizolidPosizolidPosizolid is an oxazolidinone antibiotic under investigation for the treatment of bacterial infections....
, which appears to have excellent, targeted bactericidal activity against all common gram-positive bacteria, regardless of resistance to other classes of antibiotics.
- TorezolidTorezolidTorezolid is an oxazolidinone drug in phase-II clinical trials for complicated skin and skin-structure infections , including those caused by Methicillin-resistant Staphylococcus aureus ....
is in phase-II clinical trials - RadezolidRadezolidRadezolid is a novel oxazolidinone antibiotic being developed by Rib-X Pharmaceuticals, Inc. for the treatment of serious multi-drug–resistant infections. Radezolid has completed two phase-II clinical trials...
(RX-1741) has completed some phase-II clinical trials. - CycloserineCycloserineCycloserine is an antibiotic effective against Mycobacterium tuberculosis. For the treatment of tuberculosis, it is classified as a second line drug, i.e...
is a second line drug against tuberculosisTuberculosisTuberculosis, MTB, or TB is a common, and in many cases lethal, infectious disease caused by various strains of mycobacteria, usually Mycobacterium tuberculosis. Tuberculosis usually attacks the lungs but can also affect other parts of the body...
An oxazolidinone derivative used for other purposes is rivaroxaban
Rivaroxaban
Rivaroxaban is an oral anticoagulant invented and manufactured by Bayer; in a number of countries it is marketed as Xarelto. In the United States, it is marketed by Janssen Pharmaceutica. It is the first available orally active direct factor Xa inhibitor. Rivaroxaban is well absorbed from the gut...
, which is approvedby the FDA for venous thromboembolism prophylaxis.
History
Cycloserine
Cycloserine is an antibiotic effective against Mycobacterium tuberculosis. For the treatment of tuberculosis, it is classified as a second line drug, i.e...
(4-amino-1,2-oxazolidin-3-one), a second line drug against Tuberculosis
Tuberculosis
Tuberculosis, MTB, or TB is a common, and in many cases lethal, infectious disease caused by various strains of mycobacteria, usually Mycobacterium tuberculosis. Tuberculosis usually attacks the lungs but can also affect other parts of the body...
since 1956. Developed during the nineties when several bacterial strains were becoming resistant against such antibiotics as vancomycin
Vancomycin
Vancomycin INN is a glycopeptide antibiotic used in the prophylaxis and treatment of infections caused by Gram-positive bacteria. It has traditionally been reserved as a drug of "last resort", used only after treatment with other antibiotics had failed, although the emergence of...
. Linezolid
Linezolid
Linezolid is a synthetic antibiotic used for the treatment of serious infections caused by Gram-positive bacteria that are resistant to several other antibiotics...
(Zyvox) is the first approved agent in the class.
The first commercially available 1,3-oxazolidinone antibiotic was Linezolid
Linezolid
Linezolid is a synthetic antibiotic used for the treatment of serious infections caused by Gram-positive bacteria that are resistant to several other antibiotics...
, discovered and developed by Pharmacia & Upjohn.
AstraZeneca
AstraZeneca plc is a global pharmaceutical and biologics company headquartered in London, United Kingdom. It is the world's seventh-largest pharmaceutical company measured by revenues and has operations in over 100 countries...
introduced posizolid
Posizolid
Posizolid is an oxazolidinone antibiotic under investigation for the treatment of bacterial infections....
(AZD2563).