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dc.contributor.authorRomeo, Giuseppe F.
dc.contributor.authorMateria, Luisa
dc.contributor.authorModica, Maria Nunziata
dc.contributor.authorPittal, Valeria
dc.contributor.authorSalerno, Loredana
dc.contributor.authorSiracusa, Maria Angela
dc.contributor.authorManetti, Fabrizio
dc.contributor.authorBotta, Maurizio
dc.contributor.authorMinneman, Kenneth P.
dc.date.accessioned2015-08-03T09:05:02Z
dc.date.available2015-08-03T09:05:02Z
dc.date.issued2011-07
dc.identifier.citationRomeo, G., Materia, L., Modica, M. N., Pittalà, V., Salerno, L., Siracusa, M. A., … Minneman, K. P. (2011). Novel 4-phenylpiperidine-2,6-dione derivatives. Ligands for α1-adrenoceptor subtypes. European Journal of Medicinal Chemistry, 46(7), 2676–2690. doi:10.1016/j.ejmech.2011.03.054
dc.identifier.issn02235234
dc.identifier.doi10.1016/j.ejmech.2011.03.054
dc.identifier.urihttp://hdl.handle.net/10754/561806
dc.description.abstractA number of new 4-phenylpiperidine-2,6-diones bearing at the 1-position an ω-[4-(substituted phenyl)piperazin-1-yl]alkyl moiety were designed and synthesized as ligands for the α1-adrenergic receptor (α1-AR) subtypes. Some synthesized compounds, tested in binding assays for the human cloned α1A-, α1B-, and α1D-AR subtypes, displayed affinities in the nanomolar range. Highest affinity values were found in derivatives having a butyl connecting chain between the 4-phenylpiperidine-2,6-dione and the phenylpiperazinyl moieties. 1-[4-[4-(2-Methoxyphenyl)piperazin-1-yl]butyl]-4-phenylpiperidine-2,6- dione (34) showed the best affinity for the α1A-AR (pK i = 8.74) and 10-fold selectivity compared to the other two α1-AR subtypes. Some representative compounds were also tested in order to evaluate their effects on the signal transduction pathway coupled to α1-AR subtypes. They all blocked norepinephrine-induced stimulation of inositol phospholipid hydrolysis, thus behaving as antagonists. Binding data were used to refine a previously developed pharmacophoric model for α1D-ARs. The revised model shows a highly predictive power and could be useful for the future design of high affinity α1D-AR ligands. © 2011 Elsevier Masson SAS. All rights reserved.
dc.publisherElsevier BV
dc.subjectα1-Adrenoceptor subtypes
dc.subject4-Phenylpiperidine-2,6-dione
dc.subjectLigands
dc.subjectPharmacophoric model
dc.titleNovel 4-phenylpiperidine-2,6-dione derivatives. Ligands for α1-adrenoceptor subtypes
dc.typeArticle
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Division
dc.identifier.journalEuropean Journal of Medicinal Chemistry
dc.contributor.institutionDipartimento di Scienze Del Farmaco, Universita di Catania, viale A. Doria 6, 95125 Catania, Italy
dc.contributor.institutionDipartimento Farmaco Chimico Tecnologico, Universita Degli Studi di Siena, via A. Moro, 53100 Siena, Italy
dc.contributor.institutionDepartment of Pharmacology, Emory University, 1510 Clifton Road, Atlanta, GA 30322, United States
kaust.personMinneman, Kenneth P.


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