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

Autor:	Shuzo Watanabe, Isao Sakurada, Makoto Kawai, Masanori Hizue, Mitsuhiro Kawamura, Kazunari Hattori, Tadashi Takashima, Hiroshi Nakamura, Ando Kazuo, Atsuko Ohta, Mizutani Mayumi, Hirota Masako, Isami Fujita, Yukari Matsumoto, Masaki Sudo
Rok vydání:	2007
Předmět:	N-Methylaspartate Stereochemistry medicine.drug_class Clinical Biochemistry Analgesic Pharmaceutical Science Pain Quinolones Biochemistry Chemical synthesis Receptors N-Methyl-D-Aspartate Inhibitory Concentration 50 Structure-Activity Relationship Piperidines Cytochrome P-450 CYP2D6 Inhibitors Drug Discovery medicine Structure–activity relationship Animals Enzyme Inhibitors Receptor Molecular Biology Bicyclic molecule Molecular Structure Chemistry musculoskeletal neural and ocular physiology Organic Chemistry Antagonist Receptor antagonist Ether-A-Go-Go Potassium Channels Rats nervous system Cytochrome P-450 CYP2D6 Molecular Medicine NMDA receptor
Zdroj:	Bioorganicmedicinal chemistry letters. 17(20)
ISSN:	0960-894X
Popis:	(-)-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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::79d56115c2d64610f4fdf1544988496a https://pubmed.ncbi.nlm.nih.gov/17766106 Zobrazit plný text záznamu Full Text from ScienceDirect