A new class of pyrazolo[5,1-c][1,2,4]triazines as γ-aminobutyric type A (GABAA) receptor subtype ligand: synthesis and pharmacological evaluation

The synthesis of the bicyclic core pyrazolotriazine (PT) strictly related to pyazolopyrimidine (PP), was realized. New compounds show α1 or α2 subtype selectivity. [Display omitted] A comparison between compounds with pyrazolo[1,5-a]pyrimidine structure (series 4–6) and pyrazolo[5,1-c][1,2,4]triazin...

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Published in:Bioorganic & medicinal chemistry 2018-05, Vol.26 (9), p.2475-2487
Main Authors: Guerrini, Gabriella, Ciciani, Giovanna, Daniele, Simona, Martini, Claudia, Costagli, Camilla, Guarino, Chiara, Selleri, Silvia
Format: Article
Language:English
Subjects:
Animals
Binding Sites
Cattle
Cell Membrane - metabolism
Cerebral Cortex - metabolism
Flumazenil - chemistry
Ligands
Molecular Structure
Pyrazoles - chemical synthesis
Pyrazoles - chemistry
Pyrazoles - pharmacology
Rats
Receptors, GABA-A - chemistry
Receptors, GABA-A - metabolism
Triazines - chemical synthesis
Triazines - chemistry
Triazines - pharmacology
Tritium
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Summary:The synthesis of the bicyclic core pyrazolotriazine (PT) strictly related to pyazolopyrimidine (PP), was realized. New compounds show α1 or α2 subtype selectivity. [Display omitted] A comparison between compounds with pyrazolo[1,5-a]pyrimidine structure (series 4–6) and pyrazolo[5,1-c][1,2,4]triazine core (series 9) as ligands at GABAA-receptor subtype, was evaluated. Moreover, for pyrazolotriazine derivatives having binding recognition, the interaction on recombinant rat α(1–3,5) GABAA receptor subtypes, was performed. Among these latter, emerge compounds 9c, 9k, 9l, 9m and 9n as α1-selective and 9h as α2-selective ligands.
ISSN:0968-0896
1464-3391
DOI:10.1016/j.bmc.2018.04.011