Recent advances in the development of NR2B subtype-selective NMDA receptor antagonists.
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.
Layton
Mark E
ME
Department of Medicinal Chemistry, Merck Research Laboratories, Merck & Co., West Point, PA 19486 USA. mark_layton@merck.com
Kelly
Michael J
MJ
Rodzinak
Kevin J
KJ
D000818:Animals; D018691:Excitatory Amino Acid Antagonists / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
D018691:Excitatory Amino Acid Antagonists; C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate