Carboxylate bioisosteres of pregabalin

Bioorg Med Chem Lett. 2006 Jul 1;16(13):3559-63. doi: 10.1016/j.bmcl.2006.03.083. Epub 2006 Apr 18.

Abstract

Several beta-amino tetrazole analogs of gabapentin 1 and pregabalin 2 were prepared by one of two convergent, highly efficient routes, and their affinity for the alpha(2)-delta protein examined. Two select compounds with potent affinity for alpha(2)-delta, 8a and 16a, were subsequently tested in vivo in an audiogenic seizure model and found to elicit protective effects.

MeSH terms

  • Amines / chemical synthesis
  • Amines / chemistry
  • Amines / pharmacology
  • Animals
  • Anticonvulsants / chemical synthesis*
  • Anticonvulsants / chemistry
  • Anticonvulsants / pharmacology*
  • Binding Sites
  • Carboxylic Acids / chemistry*
  • Cyclohexanecarboxylic Acids / chemical synthesis
  • Cyclohexanecarboxylic Acids / chemistry
  • Cyclohexanecarboxylic Acids / pharmacology
  • Disease Models, Animal
  • Drug Evaluation, Preclinical
  • Epilepsy, Reflex / prevention & control*
  • Gabapentin
  • Mice
  • Mice, Inbred DBA
  • Molecular Structure
  • Pregabalin
  • Protein Subunits / drug effects
  • Stereoisomerism
  • Structure-Activity Relationship
  • gamma-Aminobutyric Acid / analogs & derivatives*
  • gamma-Aminobutyric Acid / chemical synthesis
  • gamma-Aminobutyric Acid / chemistry
  • gamma-Aminobutyric Acid / pharmacology

Substances

  • Amines
  • Anticonvulsants
  • Carboxylic Acids
  • Cyclohexanecarboxylic Acids
  • Protein Subunits
  • Pregabalin
  • gamma-Aminobutyric Acid
  • Gabapentin