Substituted 2-aminothiopen-derivatives: a potential new class of GluR6-antagonists.
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.
Briel
D
D
Pharmazeutische Chemie, Institut für Pharmazie, Fakultät für Biowissenschaften, Pharmazie und Psychologie, Universität Leipzig, Brüderstr. 34, 04103 Leipzig, Germany. briel@rz.uni-leipzig.de
Rybak
A
A
Kronbach
C
C
Unverferth
K
K
D000818:Animals; D002460:Cell Line; D057166:High-Throughput Screening Assays; D006801:Humans; D020128:Inhibitory Concentration 50; D018092:Kainic Acid Receptors / Q000037:antagonists & inhibitors*; D013379:Substrate Specificity; D013876:Thiophenes / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D000097806:GluK2 Kainate Receptor
D018092:Kainic Acid Receptors; D013876:Thiophenes; D000097806:GluK2 Kainate Receptor