Substituted 2-aminothiopen-derivatives: a potential new class of GluR6-antagonists

Eur J Med Chem. 2010 Jan;45(1):69-77. doi: 10.1016/j.ejmech.2009.09.025. Epub 2009 Sep 16.

Abstract

In the course of search for new therapeutic agents against epilepsy new inhibitors for the kainate receptor subtypes GluR5 and GluR6 were synthesized. We were able to synthesize new substituted thieno[2,3-d]pyrimidines 3a,b, 4a,b, 5a,b as well as thiophene-3-carboxamides 2a-d and a multitude of substituted 4-methyl-5-phenylthiophene-3-carboxylic acids. All compounds described herein were tested for their antagonistic effect towards the kainate receptor subtypes GluR5 and GluR6. The highest activity was observed for ethyl 2-amino-4-methyl-5-phenylthiophene-3-carboxylate 1c with an IC50=0.75 microM at the GluR6 receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • GluK2 Kainate Receptor
  • High-Throughput Screening Assays
  • Humans
  • Inhibitory Concentration 50
  • Receptors, Kainic Acid / antagonists & inhibitors*
  • Substrate Specificity
  • Thiophenes / chemistry*
  • Thiophenes / pharmacology*
  • Thiophenes / toxicity

Substances

  • Receptors, Kainic Acid
  • Thiophenes