Heteroatom-substitution as a strategy for increasing the potency of competitive NMDA antagonists

P L Ornstein; M B Arnold; W H Lunn; L J Heinz; J D Leander; D Lodge; D D Schoepp

doi:10.1016/s0960-894x(98)00038-9

Heteroatom-substitution as a strategy for increasing the potency of competitive NMDA antagonists

Bioorg Med Chem Lett. 1998 Feb 17;8(4):389-94. doi: 10.1016/s0960-894x(98)00038-9.

Authors

P L Ornstein¹, M B Arnold, W H Lunn, L J Heinz, J D Leander, D Lodge, D D Schoepp

Affiliation

¹ Lilly Research Laboratories, Division of Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana 46285, USA.

PMID: 9871691
DOI: 10.1016/s0960-894x(98)00038-9

Abstract

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.

MeSH terms

Animals
Excitatory Amino Acid Antagonists / chemistry
Excitatory Amino Acid Antagonists / pharmacology*
Mice
Neurons / drug effects
Neurons / physiology
Pipecolic Acids / chemistry
Pipecolic Acids / pharmacology*
Rats
Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors*
Spinal Cord / drug effects
Spinal Cord / physiology
Structure-Activity Relationship
Tetrazoles / chemistry
Tetrazoles / pharmacology*

Substances

Excitatory Amino Acid Antagonists
Pipecolic Acids
Receptors, N-Methyl-D-Aspartate
Tetrazoles
LY 233053