168828-82-8Relevant articles and documents
Synthesis of covalent bonding MWCNT-oligoethylene linezolid conjugates and their antibacterial activity against bacterial strains
Alatorre-Barajas, José A.,Alcántar-Zavala, Eleazar,Alonso-Nú?ez, Gabriel,Cabrera, Alberto,Estrada-Zavala, Edgar,Gil-Rivas, M. Graciela,Gochi-Ponce, Y.,Medina-Franco, J. L.,Montes-ávila, Julio,Ochoa-Terán, Adrián,Reynoso-Soto, Edgar A.,Rivera-Lugo, Yazmin Yorely,Trujillo-Navarrete, Balter
, p. 28912 - 28924 (2021/09/22)
Nowadays, infectious diseases caused by drug-resistant bacteria have become especially important. Linezolid is an antibacterial drug active against clinically important Gram positive strains; however, resistance showed by these bacteria has been reported. Nanotechnology has improved a broad area of science, such as medicine, developing new drug delivery and transport systems. In this work, several covalently bounded conjugated nanomaterials were synthesized from multiwalled carbon nanotubes (MWCNTs), a different length oligoethylene chain (Sn), and two linezolid precursors (4and7), and they were evaluated in antibacterial assays. Interestingly, due to the intrinsic antibacterial activity of the amino-oligoethylene linezolid analogues, these conjugated nanomaterials showed significant antibacterial activity against various tested bacterial strains in a radial diffusion assay and microdilution method, including Gram negative strains asEscherichia coli(11 mm, 6.25 μg mL?1) andSalmonella typhi(14 mm, ≤0.78 μg mL?1), which are not inhibited by linezolid. The results show a significant effect of the oligoethylene chain length over the antibacterial activity. Molecular docking of amino-oligoethylene linezolid analogs shows a more favorable interaction of theS2-7analog in the PTC ofE. coli.
Stereocontrolled, Divergent, Al(lll)-Catalyzed Coupling of Chiral N-Aryl Epoxy Amines and CO2
Lee, Yuseop,Choi, Jonghoon,Kim, Hyunwoo
, p. 5036 - 5039 (2018/08/24)
A divergent coupling reaction was achieved between N-aryl epoxy amines and CO2. By using two different cocatalysts, tetrabutylammonium iodide (TBAI) or 4-dimethylaminopyridine (DMAP) together with an Al(III) Lewis acid, cyclic carbonates or oxazolidinones were selectively produced through two distinct reaction pathways, respectively. The proposed reaction mechanism was supported by the stereochemical determination of the products. A gram-scale production of Linezolid was successfully achieved.
A kind of linezolid intermediate, preparation method thereof, and method for preparing and enduring zolamide
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, (2017/04/04)
The invention discloses a novel Linezolid intermediate, its preparation method and a novel preparation method of Linezolid, a structure of the Linezolid key intermediate is shown as a formula (I), in the formula (I), X is fluorine, chlorine, bromine or iodine. According to the invention, the Linezolid intermediate solves the problems of poor solubility of the Linezolid intermediate, and low yield and purity of the synthesized Linezolid in the prior art. The preparation methods of the invention have the advantages of easy preparation process, easy raw material acquisition, low cost, easy purification of intermediate product and final product, high yield and purity, and are suitable for large-scale industrial production.
Synthesis and biological evaluation of novel 5-(hydroxamic acid)methyl oxazolidinone derivatives
Phillips, Oludotun A.,D'Silva, Roselyn,Bahta, Teklu O.,Sharaf, Leyla H.,Udo, Edet E.,Benov, Ludmil,Eric Walters
, p. 120 - 131 (2015/11/24)
Research activities on the oxazolidinone antibacterial class of compounds continue to focus on developing newer derivatives with improved potency, broad-spectrum activity and safety profiles superior to linezolid. Among the safety concerns with the oxazolidinone antibacterial agents is inhibition of monoamine oxidases (MAO) resulting from their structural similarity with toloxatone, a known MAO inhibitor. Diverse substitution patterns at the C-5 position of the oxazolidinone ring have been shown to significantly affect both antibacterial activity and MAO inhibition to varying degrees. Also, the antibacterial activity of compounds containing iron-chelating functionalities, such as the hydroxamic acids, 8-hydroxyquinolines and catechols have been correlated to their ability to alter iron intake and/or metabolism. Hence a series of novel 5-(hydroxamic acid)methyl oxazolidinone derivatives were synthesized and evaluated for their antibacterial and MAO-A and -B inhibitory activities. The compounds were devoid of significant antibacterial activity but most demonstrated moderate MAO-A and -B inhibitory activities. Computer modeling studies revealed that the lack of potent antibacterial activity was due to significant steric interaction between the hydroxamic acid N-OH oxygen atom and one of the G2540 5′-phosphate oxygen atoms at the bacterial ribosomal binding site. Therefore, the replacement of the 5-acetamidomethyl group of linezolid with the 5-(N-hydroxyacetamido)methyl group present in the hydroxamic acid oxazolidinone derivatives was concluded to be detrimental to antibacterial activity. Furthermore, the 5-(hydroxamic acid)methyl oxazolidinone derivatives were also less active as MAO-A and -B inhibitors compared with linezolid and the selective inhibitors clorgyline and pargyline. In general, the 5-(hydroxamic acid)methyl oxazolidinone derivatives demonstrated moderate but selective MAO-B inhibitory activity.
PROCESS FOR THE PREPARATION OF STABLE CRYSTALLINE FORM-I OF LINEZOLID, SUBSTANTIALLY FREE OF RESIDUAL SOLVENT
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Paragraph 0131; 0132, (2015/02/18)
The invention relates to a substantially pure linezolid hydroxide having R-isomer content more than about 99.9% relative to its S-isomer. Further aspect of invention provides the ambient moisture condition, which is critical for enantiomeric pure linezolid hydroxide. The obtained substantially enantiomerically pure linezolid hydroxide compound of formula-II can be subsequently converted into the linezolid compound of formula-I, having S-isomer content more than 99.9% relative to R-isomer. Further the invention provides an improved process for preparation of enantiomeric pure linezolid Form-I, wherein linezolid Form-I having the purity more than 99.9% relative to any other known polymorphic form of linezolid. The obtained enantiomeric pure linezolid Form-I can be subsequently converted into the other known polymorphic forms linezolid. The invention also provides stable and substantially solvent-free crystal of Form-I of linezolid.
PROCESS FOR PREPARATION OF CRYSTALLINE FORM I OF LINEZOLID AND ITS COMPOSITIONS
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Page/Page column 14, (2015/05/26)
The present invention relates to a process for the preparation of crystalline form I of linezolid, comprising providing a solution of linezolid in a solvent, crystallizing and recovering the solid of Linezolid in crystalline form I at elevated temperature. The present invention also relates to the use of crystalline form I of linezolid prepared by the method of the present invention for preparing pharmaceutical compositions.
Convenient synthesis of the antibiotic linezolid via an oxazolidine-2,4-dione intermediate derived from the chiral building block isoserine
Greco, Arianna,De Marco, Rossella,Tani, Sara,Giacomini, Daria,Galletti, Paola,Tolomelli, Alessandra,Juaristi, Eusebio,Gentilucci, Luca
, p. 7614 - 7620 (2015/04/22)
We describe a new synthesis of the 5-(aminomethyl)oxazolidin-3-one core of linezolid in enantiomerically pure form. The expedient cyclization of the α-hydroxy amide derived from isoserine and 3-fluoro-4-morpholinoaniline to give the corresponding (aminomethyl)oxazolidine-2,4-dione, followed by its mild selective reduction at the C(4)-position, gave linezolid in almost quantitative overall yield. The 1,3-oxazolidin-2-one core of linezolid was obtained from isoserine in just three steps and with almost quantitative overall yield; the key features of the protocol are the expedient formation of the intermediate oxazolidine-2,4-dione, and its regioselective reduction at the 4-position.
PROCESS FOR THE PREPARATION OF CRYSTALLINE LINEZOLID
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, (2013/06/05)
The present invention discloses a stable crystalline Form-I of linesolid process for preparation thereof.
Novel promising linezolid analogues: Rational design, synthesis and biological evaluation
De Rosa, Margherita,Zanfardino, Anna,Notomista, Eugenio,Wichelhaus, Thomas A.,Saturnino, Carmela,Varcamonti, Mario,Soriente, Annunziata
, p. 779 - 785 (2013/10/22)
A new series of 5-substituted oxazolidinones derived from linezolid, having urea and thiourea moieties at the C-5 side chain of the oxazolidinone ring, were prepared and their in vitro antibacterial activity was evaluated. The compound 10f demonstrated high antimicrobial activity, comparable to that of linezolid against Staphylococcus aureus.
NOVEL PROCESS FOR PREPARATION OF LINEZOLID AND ITS NOVEL INTERMEDIATES
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, (2014/01/07)
A novel process for preparing oxazolidinone antibacterial agent Linezolid including key intermediates of oxazolidinones comprising: reacting 3-fluoro-4-morpholinyl aniline with R-epichlorohydrin; carbonylation to form oxazolidinone derivative; acetylation of (5R)-5-(chloromethyl)-3-(3-fluoro-4-morpholinophenyl-oxazolidin-2-one with sodium acetate to get novel intermediate; hydrolysis of (R)-3-(3-fluoro-4-morpholinophenyl)-2-oxo-5-oxazolidinyl methyl acetate; mesylation of (R)-3-(3-fluoro-4-morpholinophenyl)-2-oxo-5-oxazolidinyl methanol; reaction of (R)-3-(3-fluoro-4-morpholinophenyl)-2-oxo-5-oxazolidinyl methyl methane sulphonate with potassium phthalimide; hydrolysis of (S)-3-(3-fluoro-4-morpholinophenyl)-2-oxo-5-oxazolidinyl methyl phthalimide with hydrazine hydrate; acetylation of (S)-3-(3-fluoro-4-morpholinophenyl)-2-oxo-5-oxazolidinyl methyl amine with acetic anhydride yields Linezolid in high yield.
