Identification
- Generic Name
- Posizolid
- DrugBank Accession Number
- DB04850
- Background
Posizolid (AZD2563) is an oxazolidinone antibiotic. In July 2002, after completion of phase I trials in December 2001, AstraZeneca announced that they were no longer pursuing the development of Posizolid, presumably due to negative trial results (though no results were reported).
- Type
- Small Molecule
- Groups
- Investigational
- Structure
Structure for Posizolid (DB04850)
- Weight
- Average: 465.41
Monoisotopic: 465.134756354 - Chemical Formula
- C21H21F2N3O7
- Synonyms
- Posizolid
- External IDs
- AZD-2563
- AZD-5847
- AZD2563
- AZD5847
Pharmacology
- Indication
For the treatment of gram-positive infections, including multiresistant strains.
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
AZD2563 is an oxazolidinone antibiotic. 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.
- Mechanism of action
AZD2563 selectively inhibits bacterial protein synthesis through binding to sites on the bacterial ribosome and prevents the formation of a functional 70S-initiation complex. Specifically, AZD2563 binds to a site on the bacterial 23S ribosomal RNA of the 50S subunit and prevents the formation of a functional 70S initiation complex, which is an essential component of the bacterial translation process.
Target Actions Organism A23S ribosomal RNA antagonistblockerEnteric bacteria and other eubacteria UAmine oxidase [flavin-containing] A Not Available Humans - Absorption
Not Available
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
- Not Available
- Route of elimination
Not Available
- Half-life
Not Available
- Clearance
Not Available
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
Clinical signs of acute toxicity lead to decreased activity, ataxia, vomiting and tremors.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAmbrisentan The excretion of Ambrisentan can be decreased when combined with Posizolid. Asunaprevir The excretion of Asunaprevir can be decreased when combined with Posizolid. Atogepant The serum concentration of Atogepant can be increased when it is combined with Posizolid. Atorvastatin The excretion of Atorvastatin can be decreased when combined with Posizolid. Axitinib The excretion of Axitinib can be decreased when combined with Posizolid. - Food Interactions
- Not Available
Categories
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as fluorobenzenes. These are compounds containing one or more fluorine atoms attached to a benzene ring.
- Kingdom
- Organic compounds
- Super Class
- Benzenoids
- Class
- Benzene and substituted derivatives
- Sub Class
- Halobenzenes
- Direct Parent
- Fluorobenzenes
- Alternative Parents
- Alkyl aryl ethers / Oxazolidinones / Aryl fluorides / Monosaccharides / Hydropyridines / Tertiary carboxylic acid amides / Carbamate esters / Isoxazoles / Heteroaromatic compounds / Secondary alcohols show 11 more
- Substituents
- 1,2-diol / Alcohol / Alkyl aryl ether / Aromatic heteromonocyclic compound / Aryl fluoride / Aryl halide / Azacycle / Azole / Carbamic acid ester / Carbonic acid derivative show 25 more
- Molecular Framework
- Aromatic heteromonocyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Mycobacterium tuberculosis
- Gram-positive Bacteria
Chemical Identifiers
- UNII
- 82V2M8K24R
- CAS number
- 252260-06-3
- InChI Key
- HBUJYEUPIIJJOS-PBHICJAKSA-N
- InChI
- InChI=1S/C21H21F2N3O7/c22-15-7-13(26-9-14(33-21(26)30)11-31-18-3-6-32-24-18)8-16(23)19(15)12-1-4-25(5-2-12)20(29)17(28)10-27/h1,3,6-8,14,17,27-28H,2,4-5,9-11H2/t14-,17+/m1/s1
- IUPAC Name
- (5R)-3-(4-{1-[(2S)-2,3-dihydroxypropanoyl]-1,2,3,6-tetrahydropyridin-4-yl}-3,5-difluorophenyl)-5-[(1,2-oxazol-3-yloxy)methyl]-1,3-oxazolidin-2-one
- SMILES
- OC[C@H](O)C(=O)N1CCC(=CC1)C1=C(F)C=C(C=C1F)N1C[C@H](COC2=NOC=C2)OC1=O
References
- General References
- Ednie LM, Jacobs MR, Appelbaum PC: Anti-anaerobic activity of AZD2563, a new oxazolidinone, compared with eight other agents. J Antimicrob Chemother. 2002 Jul;50(1):101-5. [Article]
- Wookey A, Turner PJ, Greenhalgh JM, Eastwood M, Clarke J, Sefton C: AZD2563, a novel oxazolidinone: definition of antibacterial spectrum, assessment of bactericidal potential and the impact of miscellaneous factors on activity in vitro. Clin Microbiol Infect. 2004 Mar;10(3):247-54. [Article]
- Howe RA, Wootton M, Noel AR, Bowker KE, Walsh TR, MacGowan AP: Activity of AZD2563, a novel oxazolidinone, against Staphylococcus aureus strains with reduced susceptibility to vancomycin or linezolid. Antimicrob Agents Chemother. 2003 Nov;47(11):3651-2. [Article]
- Balasubramanian V, Solapure S, Iyer H, Ghosh A, Sharma S, Kaur P, Deepthi R, Subbulakshmi V, Ramya V, Ramachandran V, Balganesh M, Wright L, Melnick D, Butler SL, Sambandamurthy VK: Bactericidal activity and mechanism of action of AZD5847, a novel oxazolidinone for treatment of tuberculosis. Antimicrob Agents Chemother. 2014;58(1):495-502. doi: 10.1128/AAC.01903-13. Epub 2013 Nov 4. [Article]
- Link [Link]
- External Links
- PubChem Compound
- 213049
- PubChem Substance
- 175426861
- ChemSpider
- 184741
- ChEMBL
- CHEMBL131854
- Wikipedia
- Posizolid
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 2 Completed Treatment Tuberculosis (TB) 1 1 Completed Basic Science Healthy Volunteers (HV) 1 1 Completed Treatment Healthy Volunteers (HV) 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.71 mg/mL ALOGPS logP 1.06 ALOGPS logP 0.78 Chemaxon logS -2.8 ALOGPS pKa (Strongest Acidic) 12.4 Chemaxon pKa (Strongest Basic) -1.8 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 7 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 125.57 Å2 Chemaxon Rotatable Bond Count 7 Chemaxon Refractivity 109.52 m3·mol-1 Chemaxon Polarizability 44.18 Å3 Chemaxon Number of Rings 4 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.952 Blood Brain Barrier + 0.5501 Caco-2 permeable - 0.6145 P-glycoprotein substrate Substrate 0.6905 P-glycoprotein inhibitor I Inhibitor 0.7726 P-glycoprotein inhibitor II Inhibitor 0.5188 Renal organic cation transporter Non-inhibitor 0.8467 CYP450 2C9 substrate Non-substrate 0.8807 CYP450 2D6 substrate Non-substrate 0.8229 CYP450 3A4 substrate Substrate 0.5849 CYP450 1A2 substrate Non-inhibitor 0.7627 CYP450 2C9 inhibitor Non-inhibitor 0.7437 CYP450 2D6 inhibitor Non-inhibitor 0.8141 CYP450 2C19 inhibitor Non-inhibitor 0.7377 CYP450 3A4 inhibitor Non-inhibitor 0.6273 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.812 Ames test Non AMES toxic 0.5366 Carcinogenicity Non-carcinogens 0.8213 Biodegradation Not ready biodegradable 0.9809 Rat acute toxicity 2.6132 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.636 hERG inhibition (predictor II) Inhibitor 0.8159
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-00lr-0009800000-4c91ab055f65bf9c9b1b Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-01zj-1009800000-dfc7539cd0c7ac7b0f2b Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-02aj-0008900000-40245a438e4ec15d26b5 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-0006-9002100000-d63e974f7c6be0b63568 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-022a-1236900000-5a390fea004cfea97c7c Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-01ox-9004700000-060cab2cba528777dd71 Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 199.7795 predictedDeepCCS 1.0 (2019) [M+H]+ 202.17506 predictedDeepCCS 1.0 (2019) [M+Na]+ 208.0876 predictedDeepCCS 1.0 (2019)
Targets
Build, predict & validate machine-learning models
Use our structured and evidence-based datasets to unlock newinsights and accelerate drug research.
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
Yes
Antagonist
Blocker
References
- Balasubramanian V, Solapure S, Iyer H, Ghosh A, Sharma S, Kaur P, Deepthi R, Subbulakshmi V, Ramya V, Ramachandran V, Balganesh M, Wright L, Melnick D, Butler SL, Sambandamurthy VK: Bactericidal activity and mechanism of action of AZD5847, a novel oxazolidinone for treatment of tuberculosis. Antimicrob Agents Chemother. 2014;58(1):495-502. doi: 10.1128/AAC.01903-13. Epub 2013 Nov 4. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- General Function
- Serotonin binding
- Specific Function
- Catalyzes the oxidative deamination of biogenic and xenobiotic amines and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral...
- Gene Name
- MAOA
- Uniprot ID
- P21397
- Uniprot Name
- Amine oxidase [flavin-containing] A
- Molecular Weight
- 59681.27 Da
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Sodium-independent organic anion transmembrane transporter activity
- Specific Function
- Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostagland...
- Gene Name
- SLCO1B1
- Uniprot ID
- Q9Y6L6
- Uniprot Name
- Solute carrier organic anion transporter family member 1B1
- Molecular Weight
- 76447.99 Da
References
- AstraZeneca: AZD5847 Oxazolidinone for the treatment of Tuberculosis [File]
Drug created at October 18, 2007 22:53 / Updated at February 21, 2021 18:51