N-{[(5S)-3-[3-fluoro-4-(morpholin-4-yl)phenyl]-2-oxo-1,3-oxazolidin-5-yl]methyl}acetamide

• ChemBase ID: 483
• Molecular Formular: C16H20FN3O4
• Molecular Mass: 337.3461032
• Monoisotopic Mass: 337.14378436
• SMILES: Fc1c(N2CCOCC2)ccc(N2C[C@@H](OC2=O)CNC(=O)C)c1
• Canonical SMILES: CC(=O)NC[C@@H]1OC(=O)N(C1)c1ccc(c(c1)F)N1CCOCC1
• InChI: InChI=1S/C16H20FN3O4/c1-11(21)18-9-13-10-20(16(22)24-13)12-2-3-15(14(17)8-12)19-4-6-23-7-5-19/h2-3,8,13H,4-7,9-10H2,1H3,(H,18,21)/t13-/m0/s1
• InChIKey: TYZROVQLWOKYKF-ZDUSSCGKSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: N-{[(5S)-3-[3-fluoro-4-(morpholin-4-yl)phenyl]-2-oxo-1,3-oxazolidin-5-yl]methyl}acetamide
• IUPAC Traditional name: linezolid
• Brand Name: Linezlid; Zyvox; Zyvoxid
• Synonyms: linezolid; Linezolid; N-{[(5S)-3-(3-fluoro-4-morpholin-4-ylphenyl)-2-oxo-1,3-oxazolidin-5-yl]methyl}acetamide; N-[[(5S)-3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]-acetamide; Linospan; Linox; PNU 100766; U 100766; (S)-N-((3-(3-Fluoro-4-morpholinophenyl)-2-oxooxazolidin-5-yl)methyl)acetamide; Zyvox; PNU-100766; U-100766; Zyvoxid; Zyvoxam; N-[[(5S)-3-[3-Fluoro-4-(4-morpholinyl)phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide; Linezolid

Database IDs

• CAS Number: 165800-03-3
• MDL Number: MFCD00937825
• PubChem SID: 160963946; 46504452
• PubChem CID: 441401

CALCULATED PROPERTIES

JChem

• Acid pKa: 14.453722
• H Acceptors: 5
• H Donor: 1
• LogD (pH = 5.5): 0.63666356
• LogD (pH = 7.4): 0.6366636
• Log P: 0.6366637
• Molar Refractivity: 84.4748 cm^3
• Polarizability: 32.025 Å^3
• Polar Surface Area: 71.11 Å^2
• Rotatable Bonds: 4
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 0.61
• LOG S: -2.37
• Solubility (Water): 1.44e+00 g/l

PROPERTIES

Physical Property

• Solubility: 3 mg/mL; Chloroform; DMSO: >20 mg/mL
• Apperance: White Solid; white to off-white powder
• Melting Point: 176-178°C
• Hydrophobicity(logP): 0.9

Safety Information

• Storage Condition: -20°C; Refrigerator
• RTECS: AC2720000
• German water hazard class: 3
• GHS Pictograms: GHS08
• GHS Signal Word: Danger
• GHS Hazard statements: H372
• GHS Precautionary statements: P314
• Storage Temperature: room temp

Pharmacology Properties

• Target Organ: Bone

Product Information

• Purity: ≥98% (HPLC); 95+%
• Salt Data: Free Base
• Empirical Formula (Hill Notation): C16H20FN3O4

DETAILS

DrugBank - DB00601

• Drug Groups: approved; investigational
• Description: Linezolid is a synthetic antibiotic, the first of the oxazolidinone class, used for the treatment of infections caused by multi-resistant bacteria including streptococcus and methicillin-resistant Staphylococcus aureus (MRSA). The drug works by inhibiting the initiation of bacterial protein synthesis.
• Indication: For the treatment of bacterial infections caused by susceptible strains of vancomycin resistant Enterococcus faecium, Staphylococcal aureus (methicillin resistant and susceptible strains), Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus agalactiae.
• Pharmacology: Linezolid is a synthetic antibacterial agent of a new class of antibiotics, the oxazolidinones, which has clinical utility in the treatment of infections caused by aerobic Gram-positive bacteria. The in vitro spectrum of activity of linezolid also includes certain Gram-negative bacteria and anaerobic bacteria. Susceptible organisms include methicillin- and vancomycin-resistant staphylococci, vancomycin-resistant enterococci, penicillin-resistant pneumococci and anaerobes. Oxazolidinones inhibit protein synthesis by binding at the P site at the ribosomal 50S subunit. Resistance to other protein synthesis inhibitors does not affect oxazolidinone activity, however rare development of oxazolidinone resistance cases, associated with 23S rRNA alterations during treatment have been reported. Linezolid inhibits bacterial protein synthesis through a mechanism of action different from that of other antibacterial agents; therefore, cross-resistance between linezolid and other classes of antibiotics is unlikely.
• Toxicity: Clinical signs of acute toxicity lead to decreased activity, ataxia, vomiting and tremors.
• Affected Organisms: Gram negative and gram positive bacteria
• Biotransformation: Linezolid is primarily metabolized by oxidation of the morpholine ring, which results in two inactive ring-opened carboxylic acid metabolites: the aminoethoxyacetic acid metabolite (A), and the hydroxyethyl glycine metabolite
• Absorption: Linezolid is rapidly and extensively absorbed after oral dosing. Maximum plasma concentrations are reached approximately 1 to 2 hours after dosing, and the absolute bioavailability is approximately 100%.
• Half Life: 4.5-5.5 hours
• Protein Binding: 31%
• Distribution: * 40 to 50 L [healthy adult volunteers]
• References: [Link] ; Park IN, Hong SB, Oh YM, Kim MN, Lim CM, Lee SD, Koh Y, Kim WS, Kim DS, Kim WD, Shim TS: Efficacy and tolerability of daily-half dose linezolid in patients with intractable multidrug-resistant tuberculosis. J Antimicrob Chemother. 2006 Sep;58(3):701-4. Epub 2006 Jul 19. [Pubmed]
• External Links: Wikipedia; RxList; PDRhealth; Drugs.com

DrugBank - DB08769

Drug information: experimental

Selleck Chemicals - S1408

Research Area: Infection
Biological Activity:
Linezolid (Zyvox) is a synthetic antibiotic used for the treatment of serious infections caused by Gram-positive bacteria that are resistant to several other antibiotics. A member of the oxazolidinone class of drugs, linezolid is active against most Gram-positive bacteria that cause disease, including streptococci, vancomycin-resistant enterococci (VRE), and methicillin-resistant Staphylococcus aureus (MRSA). [1]

Sigma Aldrich - PZ0014

Legal Information
Sold for research purposes under agreement from Pfizer Inc.
Biochem/physiol Actions
Linezolid is an oxazolidinone antimicrobial. It binds to a site on the bacterial 23S ribosomal RNA of the 50S subunit and prevents the formation of a functional 70S initiation complex, thus inhibiting bacterial mRNA translation. Linezolid is also a weak, reversible, nonselective inhibitor of monoamine oxidase.

Toronto Research Chemicals - L466500

Prototype of the oxazolidinone antimicrobials; inhibits bacterial mRNA translation.

REFERENCES

• Link
• Park IN, Hong SB, Oh YM, Kim MN, Lim CM, Lee SD, Koh Y, Kim WS, Kim DS, Kim WD, Shim TS: Efficacy and tolerability of daily-half dose linezolid in patients with intractable multidrug-resistant tuberculosis. J Antimicrob Chemother. 2006 Sep;58(3):701-4. Epub 2006 Jul 19. Pubmed
• http://en.wikipedia.org/wiki/Linezolid
• Brickner, S.J., et al.: J. Med. Chem., 39, 673 (1996)
• Ford, C.W., et al.: Antimicrob. Agents Chemother., 40, 1508 (1996)
• Rybak, M.J., et al.: Pharmacotherapy, 18, 456 (1996)
• Stevens, D.L., et al.: Clin. Infect. Dis., 34, 1481 (1996)