Article ID Journal Published Year Pages File Type
1365696 Bioorganic & Medicinal Chemistry Letters 2007 5 Pages PDF
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 IC50). This compound has improved pharmacokinetic properties compared to the prototype CP-101,606.

Graphical abstractCompound (−)-19 was identified by structure–activity relationship around CP-101,606 (1) in order to alleviate its significant PK variability and QT prolongation issues.Figure optionsDownload full-size imageDownload as PowerPoint slide

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Physical Sciences and Engineering Chemistry Organic Chemistry
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