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Current Topics in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1568-0266
ISSN (Online): 1873-4294

Recent Advances in the Development of NR2B Subtype-Selective NMDA Receptor Antagonists

Author(s): Mark E. Layton, Michael J. Kelly III and Kevin J. Rodzinak

Volume 6, Issue 7, 2006

Page: [697 - 709] Pages: 13

DOI: 10.2174/156802606776894447

Price: $65

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Abstract

Over activation of the NMDA receptor complex has been implicated in a number of neurological conditions. The use of NMDA antagonists as therapeutic agents has been limited by serious cognitive and motor side effects. Significant efforts have been reported in the development of NR2B subtype-selective antagonists, which have shown efficacy without the side effects observed with nonspecific NMDA antagonists. Classical ifenprodil-like molecules containing benzyl- and phenylpiperidines attached to a phenol or an appropriate isostere by a linker have provided valuable chemical leads as potential therapeutic agents. In this review, recent efforts in the discovery and development of structurally unique NR2B subtype-selective NMDA antagonists that do not fit the classical "ifenprodil-like" pharmacophore will be discussed.

Keywords: NMDA, subtype-selective, NR2B, antagonist, review


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