Por favor, use este identificador para citar o enlazar a este item:
http://hdl.handle.net/10261/186804
COMPARTIR / EXPORTAR:
SHARE CORE BASE | |
Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE | |
Título: | (+)-Methyl (1R,2S)-2-{[4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl]methyl}-1-phenylcyclopropanecarboxylate [(+)-MR200] derivatives as potent and selective sigma receptor ligands: Stereochemistry and pharmacological gands: Stereochemistry and Pharmacological propertiesProperties |
Autor: | Amata, Emanuele; Rescifina, Antonio; Prezzavento, Orazio; Arena, Emanuela; Dichiara, Maria; Pittalà, Valeria; Montilla-García, Ángeles; Punzo, Francesco; Merino, Pedro CSIC ORCID ; Cobos, Enrique J.; Marrazzo, Agostino | Fecha de publicación: | 2018 | Editor: | American Chemical Society | Citación: | Journal of Medicinal Chemistry 61(1): 372-384 (2018) | Resumen: | Methoxycarbonyl-1-phenyl-2-cyclopropylmethyl based derivatives cis-(+)-1a [cis-(+)-MR200], cis-(-)-1a [cis-(-)-MR201], and trans-(±)-1a [trans-(±)-MR204], have been identified as new potent sigma (σ) receptor ligands. In the present paper, novel enantiomerically pure analogues were synthesized and optimized for their σ receptor affinity and selectivity. Docking studies rationalized the results obtained in the radioligand binding assay. Absolute stereochemistry was unequivocally established by X-ray analysis of precursor trans-(+)-5a as camphorsulfonyl derivative 9. The most promising compound, trans-(+)-1d, showed remarkable selectivity over a panel of more than 15 receptors as well as good chemical and enzymatic stability in human plasma. An in vivo evaluation evidenced that trans-(+)-1d, in contrast to trans-(-)-1d, cis-(+)-1d, or cis-(-)-1d, which behave as σ1 antagonists, exhibited a σ1 agonist profile. These data clearly demonstrated that compound trans-(+)-1d, due to its σ1 agonist activity and favorable receptor selectivity and stability, provided an useful tool for the study of σ1 receptors. | Versión del editor: | https://doi.org/10.1021/acs.jmedchem.7b01584 | URI: | http://hdl.handle.net/10261/186804 | DOI: | 10.1021/acs.jmedchem.7b01584 | ISSN: | 0022-2623 | E-ISSN: | 1520-4804 |
Aparece en las colecciones: | (ISQCH) Artículos |
Ficheros en este ítem:
Fichero | Descripción | Tamaño | Formato | |
---|---|---|---|---|
accesoRestringido.pdf | 59,24 kB | Adobe PDF | Visualizar/Abrir |
CORE Recommender
PubMed Central
Citations
7
checked on 01-may-2024
SCOPUSTM
Citations
14
checked on 02-may-2024
WEB OF SCIENCETM
Citations
13
checked on 26-feb-2024
Page view(s)
125
checked on 02-may-2024
Download(s)
23
checked on 02-may-2024
Google ScholarTM
Check
Altmetric
Altmetric
Artículos relacionados:
NOTA: Los ítems de Digital.CSIC están protegidos por copyright, con todos los derechos reservados, a menos que se indique lo contrario.