| Stereochemistry | ACHIRAL |
| Molecular Formula | C14H15F3N3O6P |
| Molecular Weight | 409.2544 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
OP(O)(=O)CN1C(=O)C(=O)NC2=C1C=C(N3CCOCC3)C(=C2)C(F)(F)F
InChI
InChIKey=WZMQMKNCWDCCMT-UHFFFAOYSA-N
InChI=1S/C14H15F3N3O6P/c15-14(16,17)8-5-9-11(6-10(8)19-1-3-26-4-2-19)20(7-27(23,24)25)13(22)12(21)18-9/h5-6H,1-4,7H2,(H,18,21)(H2,23,24,25)
| Molecular Formula | C14H15F3N3O6P |
| Molecular Weight | 409.2544 |
| Charge | 0 |
| Count |
MOL RATIO
1 MOL RATIO (average) |
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
ZK 200775, also known as fanapanel, an antagonist at the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor, possesses neuroprotective efficacy in patients with acute ischemic stroke. However, the phase II of clinical trials had revealed, that this compound had led to the neuronal dysfunction and the glial cell toxicity had occurred. In addition, was shown, that the antagonization of AMPA receptors by ZK200775 lead to alterations of color and dark vision, visual acuity, cone electroretinogram (ERG) modalities and the pattern-reversal visual evoked potentials and to a lesser extent on the scotopic ERG. At the same time, ZK 200775 did not alter eye morphology, the functioning of the extraocular muscles, binocular vision, visual fields or the pupil.
Originator
Approval Year
PubMed
Sample Use Guides
A fixed dose was used for each dosage group. Group 1 received 262.5 mg over 48 h, group 2 received a total dose of 525 mg over 48 h and patients in group 3 received a total dose of 105 mg over a period of 6 h. ZK 200775 (fanapanel) was administered as an intravenous loading infusion over 30 min followed by a maintenance infusion over 47.5 h (groups 1 and 2) or 5.5 h (group 3). During the infusion, heart rhythm, body temperature, blood pressure, respiration rate and oxygen saturation were recorded at 30 min intervals for the first 4 h, thereafter at hourly intervals.
Route of Administration:
Intravenous
The potency of quinoxalinediones in inhibiting the specific binding of 3H-AMPA, 3H-6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), 3H-kainate, 3H-3-(2-carboxypiperazin-4-yl)-propyl-1phosphonate (CPP), 3H-1-[1-(2-thienyl)cyclohexyl]piperidine (TCP), 3H-dihydrochlorokynurenate (DCKA), and 3H-glycine was tested on rat cortical membranes. The receptor binding profile of ZK200775 (fanapanel) showed high affinity to 3H-AMPA (120 nM) and 3H-CNQX (32 nM) binding sites. It was 21-fold less potent at 3H-kainate (2.5 μM) and had weak affinity to the binding sites within the NMDA receptor complex such as 3H-CPP (2.8 μM), 3H-TCP (11 μM), 3H-dichlorokynurenate (2.8 μM), and 3H-glycine (5.15 μM) sites. No affinity to nonglutamate receptor binding sites was detected up to concentrations of 20–100 μM in rat cortical membrane preparations.
