• Source: 2-Oxazolidone

2-Oxazolidone is a heterocyclic organic compound containing both nitrogen and oxygen in a 5-membered ring. It is one of waste products generated in amine gas treating due to cyclization of ethanolamine carbamate.




History


The compound was first synthesized in 1888 by German chemist Siegmund Gabriel. While investigating reactions of bromoethylamine hydrobromide, he treated it with silver carbonate and isolated a product with melting point around 90–91°C. He determined its empirical formula correctly, but neither gave it a specific name not studied its properties.
16 years later Gabriel returned to the topic together with G. Eschenbach, developing a more efficient synthesis using sodium bicarbonate instead of the silver salt. They referred to the compound as "Oxäthylcarbaminsäureanhydrid" (hydroxyethylcarbamic acid anhydride), recognizing its relationship to ethanolamine and its cyclic structure. Their 1897 paper focused on optimizing the yield of oxazolidone and investigating some of its reactions, such as its conversion to 1-(2-hydroxyethyl)-3-phenylurea upon treatment with aniline.




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. Substituents at the 4 and 5 position of the oxazolidinone direct any aldol reaction 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 (Zyvox), which is available for intravenous administration and also has the advantage of having excellent oral bioavailability.
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. Note that cycloserine, while technically an oxazolidone, has a different mechanism of action and substantially different properties from the aforementioned compounds.
Contezolid (MRX-I) has reported phase 1 data and phase III data. In 2021, a new drug summary was published by ADIS Press. In June 2021, marketing approval was granted by the Chinese National Medical Products Administration (NMPA) for use of oral contezolid in moderate to severe complicated skin and skin structure infections. In June 2022, contezolid oral tablets and contezolid acefosamil IV (a prodrug of contezolid) began Phase 3 global clinical trials in moderate to severe diabetic foot infections. An additional global Phase 3 study is planned for acute bacterial skin and skin structure infections (ABSSSI) for the combination of contezolid and contezolid acefosamil.
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.
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 (FDA approval April 2000).

The first commercially available 1,3-oxazolidinone antibiotic was linezolid, discovered and developed by Pharmacia & Upjohn.

In 2002 AstraZeneca began investigating posizolid, which is in clinical trials for use in humans.




See also


Oxazolidine – the ring without the carbonyl group
Oxazolone – the unsaturated analogues




References






External links


Synthesis of Oxazolidinones – Recent Literature

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