POSIZOLID

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C21H21F2N3O7
Molecular Weight	465.4041
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

OC[C@H](O)C(=O)N1CCC(=CC1)C2=C(F)C=C(C=C2F)N3C[C@H](COC4=NOC=C4)OC3=O

InChI

InChIKey=HBUJYEUPIIJJOS-PBHICJAKSA-N

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

HIDE SMILES / InChI

Molecular Formula	C21H21F2N3O7
Molecular Weight	465.4041
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	2 / 2
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: http://adisinsight.springer.com/drugs/800013296
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/15008947 | https://www.ncbi.nlm.nih.gov/pubmed/22191526

Posizolid (AZD2563 or AZD5847) is an oxazolidinone, identified from an antibiotic research programme which aimed to synthesise agents that inhibited all Gram-positive bacteria, including multiresistant strains likely to be encountered clinically. Oxazolidinones bind to the 50S ribosomal subunit and inhibit the initiation phase of translation. Posizolid had been in phase II clinical trials for the treatment of tuberculosis. However, this study was discontinued.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Bacterial 70S ribosome 179 Target ID: CHEMBL2363135 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22191526	Inhibitor 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Tuberculosis 83 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25473035 https://www.ncbi.nlm.nih.gov/pubmed/24820085 https://www.ncbi.nlm.nih.gov/pubmed/24777103 https://www.ncbi.nlm.nih.gov/pubmed/24614239	Curative		Phase II 1132	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
5.56 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/29269434/	500 mg 1 times / day steady-state, oral dose: 500 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	POSIZOLID plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
8.4 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/29269434/	1200 mg 1 times / day steady-state, oral dose: 1200 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	POSIZOLID plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
11.54 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/29269434/	800 mg 2 times / day steady-state, oral dose: 800 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	POSIZOLID plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
7.69 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/29269434/	500 mg 2 times / day steady-state, oral dose: 500 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	POSIZOLID plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
43.97 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/29269434/	500 mg 1 times / day steady-state, oral dose: 500 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	POSIZOLID plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
73.89 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/29269434/	1200 mg 1 times / day steady-state, oral dose: 1200 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	POSIZOLID plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
93.19 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/29269434/	800 mg 2 times / day steady-state, oral dose: 800 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	POSIZOLID plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
64.75 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/29269434/	500 mg 2 times / day steady-state, oral dose: 500 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	POSIZOLID plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
5.3 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/29269434/	500 mg 1 times / day steady-state, oral dose: 500 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	POSIZOLID plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
6.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/29269434/	1200 mg 1 times / day steady-state, oral dose: 1200 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	POSIZOLID plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
6.2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/29269434/	800 mg 2 times / day steady-state, oral dose: 800 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	POSIZOLID plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
4.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/29269434/	500 mg 2 times / day steady-state, oral dose: 500 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	POSIZOLID plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
20% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/29269434/	800 mg 2 times / day steady-state, oral dose: 800 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		POSIZOLID plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Sourcing

Vendor/Aggregator	ID	URL
AAA Chemistry	AR-1H7626
ABI Chem	AC1L4U5J
ABI Chem	AC1Q6O1X
Amadis Chemical	A820111
Chemieliva Pharmaceutical Co., Ltd	PBCM0446784
Smolecule	S540026	http://www.smolecule.com/products/s540026
Synblock Inc	SB16707	http://www.synblock.com/product/252260-02-9.html
THE BioTek	bt-279568	https://www.thebiotek.com/product/inhibitors/bt-279568
eNovation Chemicals	D674106	https://www.enovationchem.com/ProductDetails.asp?ProductID=D674106

PubMed

Title	Date	PubMed
Bactericidal activity and mechanism of action of AZD5847, a novel oxazolidinone for treatment of tuberculosis.	2014	24189255

Patents

Sample Use Guides

In Vivo Use Guide

Phase 2 trial doses and schedules (500 mg once daily, 500 mg twice daily, 1200 mg once daily, and 800 mg twice daily) in subjects with newly-diagnosed sputum smear positive pulmonary tuberculosis.

Route of Administration: Oral

In Vitro Use Guide

Posizolid (AZD2563 or AZD5847) was tested against uncommonly isolated Gram-positive species to establish the breadth of its spectrum. By reference broth microdilution methods, 120 strains were tested (48 Corynebacterium spp., 10 species; 27 Listeria spp., 2 species; 11 Micrococcus spp., 2 species; 23 Bacillus spp., 3 species; 6 Stomatococcus mucilaginosus and one strain each of 5 other species) against AZD2563 and compared to eight other agents. The AZD2563/linezolid MIC(50;) % inhibited at < or =4 microg/mL were: for corynebacteria (0.25/0.25 microg/mL; 100/100%), Listeria spp. (2/2 microg/mL; 100/100%), Micrococcus spp. (1/1 microg/mL; 100/100%), Bacillus spp. (0.5/1 microg/mL; 100/100%), and S mucilaginosus (0.5/1 microg/mL; 100/100%). Using the MIC(90) values, AZD2563 was slightly more potent than linezolid (two-fold). Only four genus- species groups had AZD2563 MICs of strains at 2 microg/mL (Aerococcus, Leuconostoc, Listeria, Rhodococcus), all other isolates were inhibited by < or = 1 microg/mL.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:48:44 UTC 2023` Edited by `admin` on `Fri Dec 15 15:48:44 UTC 2023`
Record UNII	82V2M8K24R
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

POSIZOLID

Official Name

English

posizolid [INN]

Common Name

English

(5R)-3-(4-(1-((2S)-2,3-DIHYDROXYPROPANOYL)-1,2,3,6-TETRAHYDRO-4-PYRIDYL)-3,5-DIFLUOROPHENYL)-5-(1,2-OXAZOL-3-YLOXYMETHYL)-1,3-OXAZOLAN-2-ONE

Systematic Name

English

AZD-5847

Code

English

AZD2563

Code

English

AZD-2563

Code

English

Posizolid [WHO-DD]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C52588