With the aim to develop new ligands able to discriminate among the three subtypes of alfa1-adrenergic receptors (alfa1A-AR, alfa1B-AR, and alfa1D-AR), a series of new 1,2,3,9-tetrahydro-4H-carbazol-4-ones bearing a 3-[[[2-(4-hydroxyphenyl)ethyl]amino]methyl] or a 3-[[4-(2-substitutedphenyl)piperazin-1-yl]methyl] side chain were synthesized. The general structure of the new compounds is reminiscent of HEAT and RN5, two potent alfa1-AR antagonists which show high affinities for all three alfa1-AR subtypes. Some derivatives in which one ring of the tetrahydrocarbazolone system was opened were also prepared. Compounds were tested in radioligand binding assays on human cloned alfa1A-AR, alfa1B-AR, and alfa1D-AR subtypes stably expressed in HEK293 cells. They showed moderate to good affinities, although their selectivity among the receptor subtypes hardly reached one order of magnitude.
|Titolo:||new 1,2,3,9-tetrahydro-4H-carbazol-4-one derivatives. Analogues of HEAT as ligands for alpha1-adrenergic receptor subtypes|
|Data di pubblicazione:||2006|
|Citazione:||new 1,2,3,9-tetrahydro-4H-carbazol-4-one derivatives. Analogues of HEAT as ligands for alpha1-adrenergic receptor subtypes / G.ROMEO; L.MATERIA; V.PITTALA; M.MODICA; SALERNO L; M.SIRACUSA; F.RUSSO; K.P. MINNEMAN. - In: BIOORGANIC & MEDICINAL CHEMISTRY. - ISSN 0968-0896. - 14(2006), pp. 5211-5219.|
|Appare nelle tipologie:||1.1 Articolo in rivista|