Linezolid

Base Information

• Chemical Name: Linezolid
• CAS No.: 165800-03-3
• Molecular Formula: C16H20FN3O4
• Molecular Weight: 337.351
• Hs Code.: 29419000
• European Community (EC) Number: 605-416-1
• UNII: ISQ9I6J12J
• DSSTox Substance ID: DTXSID5046489
• Nikkaji Number: J709.722K
• Wikipedia: Linezolid
• Wikidata: Q411377
• NCI Thesaurus Code: C29158
• RXCUI: 190376
• Metabolomics Workbench ID: 42931
• ChEMBL ID: CHEMBL126
• Mol file: 165800-03-3.mol

Synonyms:100766, U;linezolid;linezolide;N-((3-(3-fluoro-4-morpholinylphenyl)-2-oxo-5-oxazolidinyl)methyl)acetamide;PNU 100766;PNU-100766;PNU100766;U 100766;U-100766;U100766;Zyvox

Chemical Property of Linezolid

Chemical Property:

• Appearance/Colour: White solid
• Vapor Pressure: 1.08E-13mmHg at 25°C
• Melting Point: 176-178 °C
• Refractive Index: 1.553
• Boiling Point: 585.5 °C at 760 mmHg
• PKA: 15.53±0.46(Predicted)
• Flash Point: 307.9 °C
• PSA: 71.11000
• Density: 1.302 g/cm³
• LogP: 1.64450
• Storage Temp.: Store at RT
• Solubility.: DMSO: >20mg/mL
• XLogP3: 0.7
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 6
• Rotatable Bond Count: 4
• Exact Mass: 337.14378429
• Heavy Atom Count: 24
• Complexity: 472

Purity/Quality:

99%, ^*data from raw suppliers

Linezolid ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xn
• Hazard Codes: Xn
• Statements: 20/21/22
• Safety Statements: 36-24/25

MSDS Files:

SDS file from LookChem

Total 1 MSDS from other Authors

Useful:

• Drug Classes: Antiinfective Agents
• Canonical SMILES: CC(=O)NCC1CN(C(=O)O1)C2=CC(=C(C=C2)N3CCOCC3)F
• Isomeric SMILES: CC(=O)NC[C@H]1CN(C(=O)O1)C2=CC(=C(C=C2)N3CCOCC3)F
• Recent ClinicalTrials: Pharmacokinetic Study of Linezolid for TB Meningitis
• Recent EU Clinical Trials: Evaluation of the efficacy of treatment with mucosal bacterial vaccines (autovaccines) versus suppressive antibiotic treatment in subjects with hip or knee prosthesis infections.
• Recent NIPH Clinical Trials: Efficancy and safety of dosage adjustments for linezolid in patients with renal impairment
• Indications: For the treatment of Gram-positive (G +) bacteria caused infections, including concurrent bacteremia; nosocomial pneumonia; community-acquired pneumonia ( because bacteria are not the same,pneumonia is clinically divided into hospital-acquired pneumonia and community-acquired pneumonia) and concomitant bacteremia; it can be applied for the complexity of the skin and skin and soft tissue infections, including osteomyelitis in diabetic foot infections; uncomplicated skin and skin and soft tissue infections; it is also used for the treatment of vancomycin-resistant feces enterococci. The above information is edited by the lookchem of Tian Ye.
• Uses: fully synthetic oxazolidinone antibiotics. oxazolidinone antibacterial drugs. anti-inflammatory drug. inhibit bacterial mRNA translation. Linezolid has been used in checkerboard-type drug combination MIC (minimum inhibitory concentrations) assay to determine whether ivacaftor shows positive interaction with linezolid. It has been used for the determination of minimum biofilm inhibitory concentration and for the treatment of Mycobacterium abscessus-infected Drosophila melanogaster w1118 flies. Prototype of the oxazolidinone antimicrobials; inhibits bacterial mRNA translation.
• Description: Linezolid reached the US market for the treatment of patients with infections caused by serious Gram-positive pathogens, particularly skin and soft tissue infections, communityacquired pneumonia and vancomycin-resistant enterococcal infections. Linezolid is the (S)-enantiomer of an oxazolidin-2-one synthesized in a multistep process from 3,4- difluoronitrobenzene, the key step being the cyclization of a carbamate, using a chiral epoxyester, into an enantiomerically pure oxazolidin-2-one. Linezolid can be considered as the first of a new class of antibacterial agents known as oxazolidinones, its mechanism of action being related to the inhibition of early ribosomal protein synthesis without directly inhibiting DNA or RNA synthesis. In vitro studies demonstrated that linezolid was effective, at potency levels similar to vancomycin, against staphylococcal, streptococcal and pneumococcal infections (MIC values in the range of 0.5 to 2 μg/ml), enterococcal species including VRE and VSE (MIC values about 4 μg/ml), but also other vancomycin-resistant bacteria. Linezolid is rapidly absorbed orally, its bioavailability is nearly complete at 250 mg dose giving a Cmax to MIC ratio sufficient to have pathogenic strain eradication in the clinical setting. It is considered that this new promising agent may offer new options for therapy of multi-drug infections.
• Therapeutic Function: Antibacterial
• Clinical Use: Linezolid is primarily used for the treatment of infections caused, or likely to be caused, by methicillin-resistant Staph. aureus, vancomycin-resistant enterococci and penicillin resistant Str. pneumoniae. Combination therapy with an antimicrobial active against Gram-negative bacteria is indicated if concomitant infection with a Gram-negative pathogen is suspected or confirmed.Outside of licensed indications, it has been used in the treatment of bone and joint infections, endocarditis, central nervous system infections, infections in neutropenic patients and drug-resistant tuberculosis.
• Drug interactions: Potentially hazardous interactions with other drugs Alcohol: enhanced hypotensive effect with tyramine containing products. Analgesics: avoid with nefopam; possible CNS excitation or depression with opioid analgesics. Antidepressants: increased risk of serotonergic syndrome with SSRIs and tricyclics; avoid concomitant use with duloxetine, MAOIs, moclobemide, reboxetine, venlafaxine and vortioxetine. Antiepileptics: antagonism of anticonvulsant effect, avoid with carbamazepine. Antimalarials: avoid with artemether with lumefantrine and artenimol with piperaquine Antipsychotics: CNS effects possibly increased by clozapine. Atomoxetine: avoid concomitant use. Bupropion: avoid concomitant use. Dopaminergics: risk of hypertensive crisis with co-beneldopa, co-careldopa, entacapone, levodopa, rasagiline and selegiline - avoid. Dapoxetine: increased serotonergic effects - avoid. 5HT1 receptor agonists: risk of CNS toxicity - avoid with rizatriptan, sumatriptan and zolmitriptan. Indoramin: avoid concomitant use. Opicapone: avoid concomitant use. Sympathomimetics: risk of hypertensive crisis - avoid.

Technology Process of Linezolid

There total 132 articles about Linezolid which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 98.0%

(2R)-1-{acetyl[3-fluoro-4-(morpholin-4-yl)-phenyl]-3-chloropropene}acetate → linezolid (165800-03-3,224323-50-6,872992-20-6)

Guidance literature:

With ammonium hydroxide; In methanol; at 20 - 25 ℃; for 12h;

Reference yield: 97.0%

N-(3-(3-fluoro-4-(morpholin-4-yl)phenyl)-2-oxooxazolidin-5(S)-ylmethyl)amine benzoate (1609632-44-1) + acetic anhydride (108-24-7) → linezolid (165800-03-3,224323-50-6,872992-20-6)

Guidance literature:

In dichloromethane; at 20 - 24 ℃;

Reference yield: 95.0%

bis(trichloromethyl) carbonate (32315-10-9) + N-[(2R)-3-[[3-fluoro-4-(4-morpholinyl)phenyl]amino]-2-hydroxypropyl]acetamide (333753-67-6,1561176-27-9,1666111-36-9) → linezolid (165800-03-3,224323-50-6,872992-20-6)

Guidance literature:

With triethylamine; In dichloromethane; at 0 - 20 ℃; for 2h;

upstream raw materials:

acetic anhydride

(S)-N-[[3-[3-fluoro-4-[4-morpholinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]amine

(R)-5-azidomethyl-3-(3-fluoro-4-(morpholin-4-yl)phenyl)oxazolidin-2-one

tiolacetic acid

Downstream raw materials:

(S)-3-[3'-methoxy-4'-(N-morpholino)phenyl]-5-(N-acetamidomethyl)-oxazolidin-2-one

(S)-3-(4'-N-morpholinophenyl)-5-(N-acetamidomethyl)-oxazolidin-2-one

(S)-3-[3'-(2-pyrrolyl)-4'-(N-morpholino)phenyl]-5-(N-acetamidomethyl)-oxazolidin-2-one

C₁₆H₁₉N₃O₄

Refernces

• 1、 Madhusudhan,Om Reddy,Rajesh,Ramanatham,Dubey. "Stereoselective synthesis of novel (R)- and (S)-5-azidomethyl-2-oxazolidinones from (S)-epichlorohydrin: a key precursor for the oxazolidinone class of antibacterial agents". . p. 3060 - 3062. Retrieved 2008.
• 2、 Drabina, Pavel,Macek, Karel,Pochobradsky, Jaroslav,Sedlák, Milo?,Svoboda, Jan,Vrbicky, Martin. "The asymmetric Henry reaction as synthetic tool for the preparation of the drugs linezolid and rivaroxaban". supporting information. p. 438 - 445. Retrieved 2022/05/18.
• 3、 Matsingos, Christos,Al-Adhami, Taha,Jamshidi, Shirin,Hind, Charlotte,Clifford, Melanie,Mark Sutton,Rahman, Khondaker Miraz. "Synthesis, microbiological evaluation and structure activity relationship analysis of linezolid analogues with different C5-acylamino substituents". . . Retrieved 2021/10/08.