Tedizolid Phosphate

Base Information

• Chemical Name: Tedizolid Phosphate
• CAS No.: 856867-55-5
• Molecular Formula: C₁₇H₁₆FN₆O₆P
• Molecular Weight: 450.323
• European Community (EC) Number: 836-194-6
• UNII: O7DRJ6R4DW
• ChEMBL ID: CHEMBL2105669
• DSSTox Substance ID: DTXSID30234977
• Metabolomics Workbench ID: 152106
• NCI Thesaurus Code: C152537
• Nikkaji Number: J3.050.869F
• RXCUI: 1540824
• Wikidata: Q21011227
• Mol file: 856867-55-5.mol

Synonyms:DA 7218;DA-7218;DA7218;Sivextro;tedizolid phosphate;torezolid phosphate;TR 701;TR-701

Chemical Property of Tedizolid Phosphate

Chemical Property:

• Melting Point: 256.9℃
• Boiling Point: 725.6±70.0 °C(Predicted)
• PKA: 1.81±0.10(Predicted)
• PSA: 162.60000
• Density: 1.75±0.1 g/cm3(Predicted)
• LogP: 1.57770
• Storage Temp.: under inert gas (nitrogen or Argon) at 2-8°C
• Solubility.: DMSO (Slightly, Sonicated)
• XLogP3: 0.3
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 11
• Rotatable Bond Count: 6
• Exact Mass: 450.08529741
• Heavy Atom Count: 31
• Complexity: 702

Purity/Quality:

99.0%, ^*data from raw suppliers

Tedizolid Phosphate ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CN1N=C(N=N1)C2=NC=C(C=C2)C3=C(C=C(C=C3)N4CC(OC4=O)COP(=O)(O)O)F
• Isomeric SMILES: CN1N=C(N=N1)C2=NC=C(C=C2)C3=C(C=C(C=C3)N4C[C@@H](OC4=O)COP(=O)(O)O)F
• Recent ClinicalTrials: A Study of Safety and Efficacy of MK-1986 (Tedizolid Phosphate) and Comparator in Participants From Birth to Less Than 12 Years of Age With Acute Bacterial Skin and Skin Structure Infections (MK-1986-018)
• Recent EU Clinical Trials: Oral antimicrobial treatment vs. outpatient parenteral for infective
• Indications: Tedizolid (Tedizolid Phosphate, Tidizolamide) is oxazolidinone compounds for serious Gram-positive bacterial infection treatment: Acute bacterial skin and skin structure infections and complex skin and soft tissue infections (absssi/cSSTI, IV/oral) (to be approved). Hospital Acquired/Ventilator-Associated Bacterial Pneumonia (HABP/VABP) (Clinical Phase II). SIVEXTRO is a class of oxazolidinone-based antimicrobials designed for Acute bacterial skin and skin structure infections (ABSSSI). In order to reduce the development of resistant bacteria and to maintain the effectiveness of SIVEXTRO and other antimicrobial agents, SIVEXTRO should only be used to treat or prevent infections that have been proven or strongly suspected to be bacterial-induced.
• Description: Tedizolid phosphate was approved by the US FDA in June 2014 for treatment of acute bacterial skin and skin structure infections caused by susceptible gram-positive pathogens, including MRSA. Tedizolid phosphate was discovered by Dong-A Pharmaceuticals in South Korea and developed in the USA by Cubist Pharmaceuticals (acquired from Trius Therapeutics in 2013, became a wholly owned subsidiary of Merck in 2015). The worldwide commercialization rights for tedizolid phosphate are divided between Cubist in the USA, Canada, and EU, and Bayer in Asia–Pacific, Latin America, and Africa. This second-generation oxazolidinone prodrug is rapidly converted to the active form tedizolid in the presence of endogenous phosphatases. It inhibits bacterial protein synthesis by binding to the 23S ribosomal RNA of the 50S subunit of the ribosome, preventing formation of the 70S ribosomal initiation complex, and is 4-fold to 16-fold more potent against staphylococci and enterococci compared to linezolid. 251 With high oral bioavailability (approximately 90%) and long half-life (approximately 12 hours), tedizolid phosphate is the first oxazolidinone antibiotic which can be dosed once daily either orally or intravenously.
• Uses: Tedizolid, known as TR-700, is an oral and i.v administered intracellular antibacterial drug.
• Clinical Use: Reversible non-selective MAO inhibitor: Antibacterial agent
• Drug interactions: Potentially hazardous interactions with other drugs Alcohol: some alcoholic and de-alcoholised drinks contain tyramine which can cause hypertensive crisis. Alpha-blockers: avoid concomitant use with indoramin; enhanced hypotensive effect. Analgesics: CNS excitation or depression with pethidine, other opioids and nefopam - avoid; increased risk of serotonergic effects and convulsions with tramadol - avoid. Antidepressants: enhancement of CNS effects and toxicity; avoid MAOIs, SSRIs and vortioxetine for 2 weeks after use; care with all antidepressants. Antiepileptics: antagonism of anticonvulsant effect; avoid carbamazepine with or within 2 weeks of MAOIs. Antimalarials: avoid concomitant use with artemether/lumefantrine and piperaquine with artenimol. Antipsychotics: effects enhanced by clozapine. Atomoxetine: possible increased risk of convulsions - avoid concomitant use and for 2 weeks after use. Bupropion: avoid with or for 2 weeks after MAOIs. Dapoxetine: increased risk of serotonergic effects, avoid with or for 2 weeks after MAOIs. Dexamfetamine and lisdexamfetamine: risk of hypertensive crisis, avoid with or for 2 weeks after MAOIs. Dopaminergics: avoid concomitant use with entacapone and tolcapone; hypertensive crisis with levodopa and rasagiline - avoid for at least 2 weeks after stopping MAOI; hypotension with selegiline. 5HT1 agonist: risk of CNS toxicity with sumatriptan, rizatriptan and zolmitriptan - avoid sumatriptan and rizatriptan for 2 weeks after MAOI. Metaraminol: risk of hypertensive crisis, avoid with or for 2 weeks after MAOIs. Methyldopa: avoid concomitant use. Opicapone: avoid concomitant use. Sympathomimetics: hypertensive crisis with sympathomimetics - avoid. Tetrabenazine: risk of CNS excitation and hypertension - avoid.

Technology Process of Tedizolid Phosphate

There total 26 articles about Tedizolid Phosphate 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: 97.0%

(5R)-3-{3-fluoro-4-[6-(2-methyl-2H-tetrazol-5-yl)pyridra-3-yl]phenyl}-5-(hydroxymethyl)-1,3-oxazoiidin-2-one (856866-72-3) → (R)-3-(4-(2-(2-methyltetrazol-5-yl)pyridine-5-yl)-3-fluorophenyl)-5-hydroxymethyl oxazolidin-2-one dihydrogen phosphate (1835340-19-6,856867-55-5)

Guidance literature:

With triethylamine; trichlorophosphate; In tetrahydrofuran; at 0 ℃; for 3h;

Reference yield: 96.0%

dibenzyl (R)-[3-(4-(2-(2-methyltetrazol-5-yl)pyridin-5-yl)-3-fluorophenyl)-2-oxo-5-oxazolidinyl]methyl phosphoric acid → (R)-3-(4-(2-(2-methyltetrazol-5-yl)pyridine-5-yl)-3-fluorophenyl)-5-hydroxymethyl oxazolidin-2-one dihydrogen phosphate (1835340-19-6,856867-55-5)

Guidance literature:

With palladium 10% on activated carbon; hydrogen; In methanol; water; at 50 ℃; for 12h; under 760.051 Torr;

Reference yield: 80.3%

[(R)-3-(4-(2-(2-methyltetrazol-5-yl)pyridin-5-yl)-3-fluorophenyl)-2-oxo-5-oxazolidinyl]methyl disodium phosphate → (R)-3-(4-(2-(2-methyltetrazol-5-yl)pyridine-5-yl)-3-fluorophenyl)-5-hydroxymethyl oxazolidin-2-one dihydrogen phosphate (1835340-19-6,856867-55-5)

Guidance literature:

With hydrogenchloride; In tetrahydrofuran; water; for 0.25h; pH=3;

upstream raw materials:

(5R)-3-{3-fluoro-4-[6-(2-methyl-2H-tetrazol-5-yl)pyridra-3-yl]phenyl}-5-(hydroxymethyl)-1,3-oxazoiidin-2-one

2,5-dibromopyridine

2-Cyano-5-bromopyridine

5-bromo-2-(2-methyl-2H-tetrazol-5-yl)pyridine

Refernces

• 1、 -. "Purification method of tedizolid phosphate". Paragraph 0036. . Retrieved 2021/06/21.
• 2、 -. "Preparation method of high-purity tedizolid phosphate". Paragraph 0020. . Retrieved 2020/05/30.