Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1365696 | Bioorganic & Medicinal Chemistry Letters | 2007 | 5 Pages |
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
Related Topics
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Authors
Makoto Kawai, Kazuo Ando, Yukari Matsumoto, Isao Sakurada, Masako Hirota, Hiroshi Nakamura, Atsuko Ohta, Masaki Sudo, Kazunari Hattori, Tadashi Takashima, Masanori Hizue, Shuzo Watanabe, Isami Fujita, Mayumi Mizutani, Mitsuhiro Kawamura,