Synthesis and receptor binding of thiophene bioisosteres of potent GluN2B ligands with a benzo[7]annulene-scaffold.

ABSTRACT: The involvement of NMDA receptors containing the GluN2B subunit in neurodegenerative disorders including Alzheimer's and Parkinson's disease renders this NMDA receptor subtype an interesting pharmacological target. The aim of this study was the bioisosteric replacement of benzene, methoxybenzene and aniline moieties of known potent GluN2B selective NMDA receptor antagonists by a thiophene ring. In a nine-step synthesis starting from commercially available propionic acid 9 the thiophene derivative 7a was obtained as a bioisostere of the potent GluN2B ligands cis-3 and trans-3. [7]Annuleno[b]thiophene 8a without a benzylic OH moiety was prepared in a six-step synthesis starting from carboxylic acid 18. 8a represents a bioi

SUBMITTER: Baumeister S 

PROVIDER: S-EPMC6390687 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature