3-(2-Carbamoylvinyl)-4,5-dimethylpyrrole-2-carboxylic acids as ligands at the NMDA glycine-binding site: a study on the 2-carbamoylvinyl chain modification

Farmaco. 1999 Jan-Feb;54(1-2):101-11. doi: 10.1016/s0014-827x(98)00110-4.

Abstract

Twenty 4,5-dimethylpyrrole-2-carboxylic acids (5a-t) with different 2-carbamoylvinyl chains in position 3 were prepared to further investigate the relationships between structure and in vitro affinity for the strychnine-insensitive glycine-binding site. None of these compounds was superior to (E)-3-(N-phenyl-2-carbamoylvinyl)-4,5-dimethylpyrrole-2-carb oxylic acid III (pKi = 6.70), which was taken as a reference standard, but overall the results obtained indicate that the N-phenyl-2-carbamoylvinyl substituent of III may be replaced with the N-(1-adamantyl)-2-carbamoylvinyl group as in 5h (pKi = 6.20) without considerable loss of affinity. This finding adds to previous knowledge.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carboxylic Acids / chemical synthesis*
  • Carboxylic Acids / chemistry
  • Carboxylic Acids / metabolism
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism
  • Cerebral Cortex / ultrastructure
  • Glycine Agents / chemical synthesis*
  • Glycine Agents / chemistry
  • Glycine Agents / metabolism
  • In Vitro Techniques
  • Ligands
  • Pyrroles / chemical synthesis*
  • Pyrroles / chemistry
  • Pyrroles / metabolism
  • Rats
  • Receptors, N-Methyl-D-Aspartate / drug effects*
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Structure-Activity Relationship
  • Strychnine / pharmacology
  • Synaptosomes / drug effects
  • Synaptosomes / metabolism

Substances

  • Carboxylic Acids
  • Glycine Agents
  • Ligands
  • Pyrroles
  • Receptors, N-Methyl-D-Aspartate
  • Strychnine