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

Gabriella Guerrini; Giovanna Ciciani; Simona Daniele; Claudia Martini; Camilla Costagli; Chiara Guarino; Silvia Selleri

doi:10.1016/j.bmc.2018.04.011

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

Bioorg Med Chem. 2018 May 15;26(9):2475-2487. doi: 10.1016/j.bmc.2018.04.011. Epub 2018 Apr 4.

Authors

Gabriella Guerrini¹, Giovanna Ciciani², Simona Daniele³, Claudia Martini³, Camilla Costagli², Chiara Guarino², Silvia Selleri²

Affiliations

¹ Dipartimento NEUROFARBA, Sezione Farmaceutica e Nutraceutica, Università degli Studi di Firenze, Italy. Electronic address: gabriella.guerrini@unifi.it.
² Dipartimento NEUROFARBA, Sezione Farmaceutica e Nutraceutica, Università degli Studi di Firenze, Italy.
³ Dipartimento FARMACIA, Università degli Studi di Pisa, Italy.

PMID: 29650463
DOI: 10.1016/j.bmc.2018.04.011

Abstract

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 GABA_A-receptor subtype, was evaluated. Moreover, for pyrazolotriazine derivatives having binding recognition, the interaction on recombinant rat α(1-3,5) GABA_A receptor subtypes, was performed. Among these latter, emerge compounds 9c, 9k, 9l, 9m and 9n as α1-selective and 9h as α2-selective ligands.

MeSH terms

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

Substances

Ligands
Pyrazoles
Receptors, GABA-A
Triazines
Tritium
Flumazenil