(Z)-1-{2,4-bis[(sodiooxy)sulfonyl]phenyl}-N-tert-butylmethenimine oxide

• ChemBase ID: 73077
• Molecular Formular: C11H13NNa2O7S2
• Molecular Mass: 381.33296
• Monoisotopic Mass: 380.99288232
• SMILES: c1(ccc(cc1S(=O)(=O)O[Na])S(=O)(=O)O[Na])/C=[N+](/C(C)(C)C)\[O-]
• Canonical SMILES: [Na]OS(=O)(=O)c1cc(ccc1/C=[N+](/C(C)(C)C)\[O-])S(=O)(=O)O[Na]
• InChI: InChI=1S/C11H15NO7S2.2Na/c1-11(2,3)12(13)7-8-4-5-9(20(14,15)16)6-10(8)21(17,18)19;;/h4-7H,1-3H3,(H,14,15,16)(H,17,18,19);;/q;2*+1/p-2/b12-7-
• InChIKey: XLZOVRYBVCMCGL-BPNVQINPSA-L

NAMES AND DATABASE IDS

Names

• IUPAC name: (Z)-1-{2,4-bis[(sodiooxy)sulfonyl]phenyl}-N-tert-butylmethenimine oxide
• IUPAC Traditional name: (Z)-1-[2,4-bis(sodiooxysulfonyl)phenyl]-N-tert-butylmethenimine oxide
• Synonyms: Cerovive; Disufenton sodium; NXY-059

Database IDs

• CAS Number: 168021-79-2
• PubChem SID: 162037997
• PubChem CID: 49867944

CALCULATED PROPERTIES

• H Acceptors: 5
• H Donor: 0
• LogD (pH = 5.5): 0.8307999
• LogD (pH = 7.4): 0.8308
• Log P: 0.8308
• Molar Refractivity: 75.6747 cm^3
• Polarizability: 34.0273 Å^3
• Polar Surface Area: 115.49 Å^2
• Rotatable Bonds: 6
• Lipinski's Rule of Five: true

PROPERTIES

Safety Information

• Storage Condition: -20°C

Product Information

• Salt Data: Free Base

DETAILS

Selleck Chemicals - S6002

Research Area

• Description: Neurological Disease

Biological Activity

• Description: NXY-059 (Cerovive) is a novel nitrone, shows efficacious neuroprotective effects.
• In Vitro: NXY-059 is more soluble than the spin trapping agent α-phenyl-N-tert-butyl nitrone (PBN). ^[1] In an in vitro blood-brain barrier (BBB) model, 250 mM of NXY-059 administered at the onset or up to 4 h after oxygen glucose deprivation (OGD) produces a significant reduction in the increased BBB permeability caused by OGD. Furthermore, OGD produces a huge influx of tissue plasminogen activator across the BBB, which is substantially reduced by NXY-059. ^[2]
• In Vivo: NXY-059 reduces infarct volume in rats subjected to 2 hours of middle cerebral artery occlusion in a dose-dependent manner. At equimolar doses (3.0 mg/kg for NXY-059 and 1.4 mg/kg for PBN), NXY-059 is more efficacious than PBN. Similar results are obtained when a recovery period of 7 days is allowed. The window of therapeutic opportunity for NXY-059 is 3 to 6 hours after the start of recirculation. ^[1] NXY-059, a free radical-trapping agent, has a substantial protective effect, lessening the disability caused by an experimentally induced stroke in a primate species. NXY-059 treatment reduces the overall amount of brain damage by >50% of saline-treatment values, with similar levels of protection afforded to both white and gray matter. ^[3] Treatment with NXY-059 (50 mg/kg subcutaneous plus 8.8 mg/kg/h for 3 days subcutaneous delivered via implanted osmotic pumps) significantly decreases neurological impairment following intracerebral hemorrhage in rat, and reduces the neutrophil infiltrate observed 48 hours post-hemorrhage in the vicinity of the hematoma, and the number of TUNEL-positive cells 48 hours post-hemorrhage at the hematoma margin. ^[4]
• Clinical Trials: NXY-059 is now under the Phase 2 clinical trial in patients with prelapsed or refractory multiple myeloma.

Combination Therapy

• Description: NXY-059, combined with Bortezomib plus Dexamethasone, is now under the Phase 1 clinical trial in patients with prelapsed or refractory multiple myeloma.

Protocol

• Protocol: Animal Study ^[1]
• Animal Models: Monofilament fishing line is used to produce occlusion and neurologic deficit in male Wistar rats
• Formulation: NXY-059 is dissolved in physiological saline.
• Doses: 0.3, 3.0 or 30 mg/kg
• Administration: Administered into the right jugular vein.

References

• References: [1] Kuroda S, et al, J Cereb Blood Flow Metab, 1999, 19(7), 778-787.
• References: [2] Culot M, et al, Brain Res, 2009, 19(1294), 144-152.
• References: [3] Marshall JW, et al, Stroke, 2001, 32(1), 190-198.
• References: [4] Peeling J, et al, Neuropharmacology, 2001, 40(3), 433-439.

REFERENCES

• Kuroda S, et al, J Cereb Blood Flow Metab, 1999, 19(7), 778-787.
• Culot M, et al, Brain Res, 2009, 19(1294), 144-152.
• Marshall JW, et al, Stroke, 2001, 32(1), 190-198.
• Peeling J, et al, Neuropharmacology, 2001, 40(3), 433-439.