Design, synthesis, and evaluation of phenylpiperazine-phenylacetate derivatives as rapid recovery hypnotic agents.
Bioorg Med Chem Lett
; 57: 128497, 2022 02 01.
Article
em En
| MEDLINE
| ID: mdl-34896213
In this paper, we designed and synthesized a series of novel phenylpiperazine-phenylacetate derivatives as rapid recovery hypnotic agents. The best compound 10 had relatively high affinity for the GABAA receptor and low affinity for thirteen other off-target receptors. In three animal models (mice, rats, and rabbits), compound 10 exerted potent hypnotic effects (HD50 = 5.2 mg/kg in rabbits), comparable duration of the loss of righting reflex (LORR), and significant shorter recovery time (time to walk) than propanidid. Furthermore, compound 10 (TI = 18.1) showed higher safety profile than propanidid (TI = 14.7) in rabbits. Above results suggested that compound 10 may have predictable and rapid recovery profile in anesthesia.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fenilacetatos
/
Piperazinas
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Hipnóticos e Sedativos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article