Subtype selective NMDA receptor antagonists: evaluation of some novel alkynyl analogues

A benzylpiperidine analogue with an acetylenic linker, 5-(3-[4-(4-fluorobenzyl)-piperidin-1-yl]-prop-1-ynyl)-1,3-dihydrobenzimidazol-2-one (3), was identified as a chemical lead with excellent activity at the NR1A/2B receptor (IC50=3 nM). Efforts to optimize this activity led to focused modification...

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Veröffentlicht in:	Bioorganic & medicinal chemistry letters 2004-03, Vol.14 (5), p.1213-1216
Hauptverfasser:	KORNBERG, Brian E, NIKAM, Sham S, WRIGHT, Jon L, KESTEN, Suzanne R, MELTZER, Leonard T, COUGHENOUR, Linda, BARR, Bridget, SERPA, Kevin A, MCCORMICK, Julie
Format:	Artikel
Sprache:	eng
Schlagworte:	Alkynes - chemistry Alkynes - metabolism Alkynes - pharmacology Animals Biological and medical sciences Brain - drug effects Brain - metabolism Drug Evaluation, Preclinical - methods Excitatory Amino Acid Antagonists - chemistry Excitatory Amino Acid Antagonists - metabolism Excitatory Amino Acid Antagonists - pharmacology Glutamatergic system (aspartate and other excitatory aminoacids) Medical sciences Neuropharmacology Neurotransmitters. Neurotransmission. Receptors Pharmacology. Drug treatments Rats Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors Receptors, N-Methyl-D-Aspartate - metabolism
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Zusammenfassung:	A benzylpiperidine analogue with an acetylenic linker, 5-(3-[4-(4-fluorobenzyl)-piperidin-1-yl]-prop-1-ynyl)-1,3-dihydrobenzimidazol-2-one (3), was identified as a chemical lead with excellent activity at the NR1A/2B receptor (IC50=3 nM). Efforts to optimize this activity led to focused modifications around the structural motif of 3. The synthesis and SAR studies are discussed.
ISSN:	0960-894X 1464-3405
DOI:	10.1016/j.bmcl.2003.12.049