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

Brian E Kornberg; Sham S Nikam; Jon L Wright; Suzanne R Kesten; Leonard T Meltzer; Linda Coughenour; Bridget Barr; Kevin A Serpa; Julie McCormick

doi:10.1016/j.bmcl.2003.12.049

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

Bioorg Med Chem Lett. 2004 Mar 8;14(5):1213-6. doi: 10.1016/j.bmcl.2003.12.049.

Authors

Brian E Kornberg¹, Sham S Nikam, Jon L Wright, Suzanne R Kesten, Leonard T Meltzer, Linda Coughenour, Bridget Barr, Kevin A Serpa, Julie McCormick

Affiliation

¹ Department of Chemistry, Pfizer Global Research and Development, 2800 Plymouth Road, Ann Arbor, MI 48105, USA. [email protected]

PMID: 14980668
DOI: 10.1016/j.bmcl.2003.12.049

Abstract

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.

MeSH terms

Alkynes / chemistry*
Alkynes / metabolism
Alkynes / pharmacology
Animals
Brain / drug effects
Brain / metabolism
Drug Evaluation, Preclinical / methods
Excitatory Amino Acid Antagonists / chemistry*
Excitatory Amino Acid Antagonists / metabolism
Excitatory Amino Acid Antagonists / pharmacology
Rats
Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors*
Receptors, N-Methyl-D-Aspartate / metabolism

Substances

Alkynes
Excitatory Amino Acid Antagonists
Receptors, N-Methyl-D-Aspartate