2. Academic Validation
  3. Discovery of (-)-6-[2-[4-(3-fluorophenyl)-4-hydroxy-1-piperidinyl]-1-hydroxyethyl]-3,4-dihydro-2(1H)-quinolinone--a potent NR2B-selective N-methyl D-aspartate (NMDA) antagonist for the treatment of pain

Discovery of (-)-6-[2-[4-(3-fluorophenyl)-4-hydroxy-1-piperidinyl]-1-hydroxyethyl]-3,4-dihydro-2(1H)-quinolinone--a potent NR2B-selective N-methyl D-aspartate (NMDA) antagonist for the treatment of pain

  • Bioorg Med Chem Lett. 2007 Oct 15;17(20):5558-62. doi: 10.1016/j.bmcl.2007.08.014.
Makoto Kawai 1,  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
Affiliations

Affiliation

  • 1 Discovery Chemistry, Pfizer Global Research & Development, Nagoya laboratories, 5-2 Taketoyo, Aichi 470-2393, Japan.
PMID: 17766106 DOI: 10.1016/j.bmcl.2007.08.014
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.

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