Heteroatom-substitution as a strategy for increasing the potency of competitive NMDA antagonists.
We report the synthesis and characterization of compounds that are competitive NMDA receptor antagonists. Significant increases in affinity and potency were obtained by incorporation of a heteroatom into the substructure of the tetrazole-substituted amino acid LY233053.
Ornstein
P L
PL
Lilly Research Laboratories, Division of Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana 46285, USA.
Arnold
M B
MB
Lunn
W H
WH
Heinz
L J
LJ
Leander
J D
JD
Lodge
D
D
Schoepp
D D
DD
D000818:Animals; D018691:Excitatory Amino Acid Antagonists / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D010875:Pipecolic Acids / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology; D013329:Structure-Activity Relationship; D013777:Tetrazoles / Q000737:chemistry / Q000494:pharmacology*
D018691:Excitatory Amino Acid Antagonists; D010875:Pipecolic Acids; D016194:Receptors, N-Methyl-D-Aspartate; D013777:Tetrazoles; C066685:LY 233053