Posizolid

Names

[ Name ]:
Posizolid

[Synonym ]:
(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
(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-oxazolidin-2-one
Posizolid
(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
AZD2563
(5R)-3-(4-{1-[(2S)-2,3-Dihydroxypropanoyl]-1,2,3,6-tetrahydro-4-pyridinyl}-3,5-difluorophenyl)-5-[(1,2-oxazol-3-yloxy)methyl]-1,3-oxazolidin-2-one
(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
2-Oxazolidinone, 3-[4-[1-[(2S)-2,3-dihydroxy-1-oxopropyl]-1,2,3,6-tetrahydro-4-pyridinyl]-3,5-difluorophenyl]-5-[(3-isoxazolyloxy)methyl]-, (5R)-
Posizolid [INN]

Biological Activity

[Description]:

Posizolid (AZD2563), an oxazolidinone antibiotic, is developed by AstraZeneca for the study of bacterial infections. Posizolid shows very good anti-mycobacterial activity[1].

[Related Catalog]:

Research Areas >> Infection

Signaling Pathways >> Others >> Others

[Target]

Posizolid shows very good anti-mycobacterial activity[1].

[In Vitro]

Posizolid is determined the activity of against 250 highly resistant pneumococci and 267 drug-susceptible isolates. Posizolid MICs for 50 and 90% of the strains tested are 1 and 2 μg/ml and 0.5 and 1 μg/ml, respectively, for the two isolate groups[2].

[In Vivo]

AZD5847 DSP (AZD2563 is prodrug) could not be detected in plasma 5 min after oral administration, suggesting rapid conversion of the prodrug to the parent molecule. In PK analysis, AZD5847(5 mg/kg) shows a low clearance (4.7 ml/min/kg) and volume of distribution (0.5 liter/kg) in mice, the half-life is 1.3 h[3]. Animal Model: Male BALB/c mice, aged 6 to 8 weeks, 30 to 40 g[3]. Dosage: 3, 10, 30, 100, 300, 600, and 900 mg/kg Administration: oral; collect blood samples at 5 min, 10 min, 15 min, 30 min, 1 h, 2 h, 4 h, 6 h, and 24 h Result: AZD5847 DSP can’t be detected in plasma 5 min. Animal Model: Male BALB/c mice, aged 6 to 8 weeks, 30 to 40 g[3]. Dosage: 250 mg/kg Administration: oral; collect blood and BAL fluid samples at 5 min, 15 min, 30 min, 1 h, 2 h, 4 h, 8 h, 16 h, 24 h, and 48 h Result: AZD5847(5 mg/kg) shows a low clearance (4.7 ml/min/kg) and volume of distribution (0.5 liter/kg) in mice, the half-life is 1.3 h.

[References]

[1]. Kumar D, et al. The anti-tuberculosis agents under development and the challenges ahead. Future Med Chem. 2015;7(15):1981-2003.

[2]. Baum SE, et al. Comparative activities of the oxazolidinone AZD2563 and linezolid against selected recent North American isolates of Streptococcus pneumoniae. Antimicrob Agents Chemother. 2002;46(9):3094-3095.

[3]. Balasubramanian V, et al. Pharmacokinetic and pharmacodynamic evaluation of AZD5847 in a mouse model of tuberculosis. Antimicrob Agents Chemother. 2014;58(7):4185-4190.

Chemical & Physical Properties

[ Density]:
1.5±0.1 g/cm3

[ Boiling Point ]:
724.5±60.0 °C at 760 mmHg

[ Molecular Formula ]:
C₂₁H₂₁F₂N₃O₇

[ Molecular Weight ]:
465.404

[ Flash Point ]:
392.0±32.9 °C

[ Exact Mass ]:
465.134766

[ PSA ]:
125.57000

[ LogP ]:
1.34

[ Vapour Pressure ]:
0.0±2.5 mmHg at 25°C

[ Index of Refraction ]:
1.596