3-Arylpiperazinylethyl-1H-pyrrolo[2,3-d]pyrimidine-2,4(3H,7H)-dione derivatives as novel, high-affinity and selective alpha(1)-adrenoceptor ligands.
The discovery of a new series of selective and high-affinity alpha(1)-adrenoceptor (alpha(1)-AR) ligands, characterized by a 1H-pyrrolo[2,3-d]-pyrimidine-2,4(3H,7H)-dione system, is described in this paper. Some synthesized compounds, including 20, 22, and 30, displayed affinity in the nanomolar range for alpha(1)-ARs and substantial selectivity with respect to 5-HT(1A) and dopaminergic D(1) and D(2) receptors. Functional assays, performed on selected derivatives, showed antagonistic properties.
Pittalà
Valeria
V
Dipartimento di Scienze Farmaceutiche, Università di Catania, viale A. Doria 6, 95125 Catania, Italy. vpittala@unict.it
Romeo
Giuseppe
G
Salerno
Loredana
L
Siracusa
Maria Angela
MA
Modica
Maria
M
Materia
Luisa
L
Mereghetti
Ilario
I
Cagnotto
Alfredo
A
Mennini
Tiziana
T
Marucci
Gabriella
G
Angeli
Piero
P
Russo
Filippo
F
D002713:Chlorine / Q000737:chemistry; D015259:Dopamine Agents / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007700:Kinetics; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D010879:Piperazines / Q000737:chemistry / Q000494:pharmacology*; D011485:Protein Binding; D011744:Pyrimidinones / Q000737:chemistry; D011758:Pyrroles / Q000737:chemistry*; D018340:Receptors, Adrenergic, alpha-1 / Q000737:chemistry* / Q000378:metabolism; D011985:Receptors, Serotonin / Q000737:chemistry; D044263:Receptors, Serotonin, 5-HT1 / Q000737:chemistry; D013997:Time Factors
D015259:Dopamine Agents; D008024:Ligands; D010879:Piperazines; D011744:Pyrimidinones; D011758:Pyrroles; D018340:Receptors, Adrenergic, alpha-1; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D002713:Chlorine