New Piperazine Derivatives of 6-Acetyl-7-hydroxy-4-methylcoumarin as 5-HT(1A) Receptor Agents

A series of 15 new derivatives of 6-acetyl-7-hydroxy-4-methylcoumarin containing a piperazine group were designed with the help of computational methods and were synthesized to study their affinity for the serotonin 5-HT(1A) and 5-HT(2A) receptors. Among them, 6-acetyl-7-{4-[4-(3-bromophenyl)piperaz...

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Detalles Bibliográficos
Autores principales: Ostrowska, Kinga, Leśniak, Anna, Gryczka, Weronika, Dobrzycki, Łukasz, Bujalska-Zadrożny, Magdalena, Trzaskowski, Bartosz
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9917830/
https://www.ncbi.nlm.nih.gov/pubmed/36769117
http://dx.doi.org/10.3390/ijms24032779
Descripción
Sumario:A series of 15 new derivatives of 6-acetyl-7-hydroxy-4-methylcoumarin containing a piperazine group were designed with the help of computational methods and were synthesized to study their affinity for the serotonin 5-HT(1A) and 5-HT(2A) receptors. Among them, 6-acetyl-7-{4-[4-(3-bromophenyl)piperazin-1-yl]butoxy}-4-methylchromen-2-one (4) and 6-acetyl-7-{4-[4-(2-chlorophenyl)piperazin-1-yl]butoxy}-4-methylchromen-2-one (7) exhibited excellent activity for 5-HT(1A) receptors with Ki values 0.78 (0.4–1.4) nM and 0.57 (0.2–1.3) nM, respectively, comparable to the Ki values of 8-OH-DPAT (0.25 (0.097–0.66) nM). The equilibrium dissociation constant values of the tested compounds showed differential intrinsic activities of the agonist and antagonist modes.

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