PlumX Metrics
Embed PlumX Metrics

Synthesis, ionotropic glutamate receptor binding affinity, and structure-activity relationships of a new set of 4,5-dihydro-8-heteroaryl-4-oxo-1,2,4-triazolo[1,5-a]quinoxaline-2- carboxylates analogues of TQX-173

Journal of Medicinal Chemistry, ISSN: 0022-2623, Vol: 44, Issue: 19, Page: 3157-3165
2001
  • 43
    Citations
  • 0
    Usage
  • 13
    Captures
  • 0
    Mentions
  • 0
    Social Media
Metric Options:   Counts1 Year3 Year

Metrics Details

Article Description

A series of 4,5-dihydro-4-oxo-1,2,4-triazolo[1,5-a] quinoxaline-2-carboxylates analogues of TQX-173 (1b), bearing different nitrogen-containing heterocycles at position-8, were synthesized as AMPA receptor antagonists. All the reported compounds were also biologically evaluated for their binding at glycine/NMDA and KA receptors to better assess their selectivity toward the AMPA receptor. Structure-activity relationships (SAR) on these TQX derivatives have evidenced that the precise positioning of the nitrogen atoms and the specific electronic topography of the 8-heteroaromatic ring are both important for the anchoring to the AMPA receptor. In fact, it has been well-established that the presence of a N-nitrogen-containing heterocycle at position-8 of the TQX framework is an essential feature for potent and selective AMPA receptor antagonists. Functional antagonism at both AMPA receptor and NMDA receptor-ion channel complex was evaluated by assessing the ability of some selected compounds to inhibit depolarization induced by 5 μM AMPA or NMDA in mouse cortical wedge preparations.

Bibliographic Details

Daniela Catarzi; Vittoria Colotta; Flavia Varano; Guido Filacchioni; Alessandro Galli; Chiara Costagli; Vincenzo Carlà

American Chemical Society (ACS)

Biochemistry, Genetics and Molecular Biology; Pharmacology, Toxicology and Pharmaceutics

Provide Feedback

Have ideas for a new metric? Would you like to see something else here?Let us know