Abstract
(-)-6-[2-[4-(3-Fluorophenyl)-4-hydroxy-1-piperidinyl]-1-hydroxyethyl]-3,4-dihydro-2(1H)-quinolinone was identified as an orally active NR2B-subunit selective N-methyl-d-aspartate (NMDA) receptor antagonist. It has very high selectivity for NR2B subunits containing NMDA receptors versus the HERG-channel inhibition (therapeutic index=4200 vs NR2B binding IC(50)). This compound has improved pharmacokinetic properties compared to the prototype CP-101,606.
MeSH terms
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Animals
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Cytochrome P-450 CYP2D6 / metabolism
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Cytochrome P-450 CYP2D6 Inhibitors
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology
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Ether-A-Go-Go Potassium Channels / metabolism
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Inhibitory Concentration 50
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Molecular Structure
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N-Methylaspartate / antagonists & inhibitors*
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N-Methylaspartate / metabolism*
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Pain* / drug therapy
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Piperidines / chemistry*
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Piperidines / pharmacology
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Quinolones / chemistry*
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Quinolones / pharmacology
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Rats
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Receptors, N-Methyl-D-Aspartate / metabolism*
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Structure-Activity Relationship
Substances
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6-(2-(4-(3-fluorophenyl)-4-hydroxy-1-piperidinyl)-1-hydroxyethyl)-3,4-dihydro-2(1H)-quinolinone
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Cytochrome P-450 CYP2D6 Inhibitors
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Enzyme Inhibitors
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Ether-A-Go-Go Potassium Channels
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NR2B NMDA receptor
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Piperidines
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Quinolones
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Receptors, N-Methyl-D-Aspartate
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N-Methylaspartate
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Cytochrome P-450 CYP2D6