Design, synthesis, and alpha(1)-adrenoceptor binding properties of new arylpiperazine derivatives bearing a flavone nucleus as the terminal heterocyclic molecular portion.
Following our research project aimed at obtaining new compounds with high affinity and selectivity toward alpha(1)-adrenoceptors (AR), a new class of piperazine derivatives was designed, synthesized and biologically tested. The new compounds 1-13 are characterized by a flavone system linked, through an ethoxy or propoxy spacer, to a phenyl- or pyridazinone-piperazine moiety. Biological data showed an interesting profile for the phenylpiperazine subclass found to have a nanomolar affinity toward alpha(1)-AR, and less pronounced affinity for alpha(2)-AR and the 5-HT(1A) serotoninergic receptor. A discussion on the structure-activity relationship (SAR) of such compounds is also reported, on the basis of the flavone substitution pattern, length and functionalization of the spacer, and disruption of the phenylpiperazine system.
Betti
Laura
L
Dipartimento di Psichiatria, Neurobiologia, Farmacologia e Biotecnologie, Università di Pisa, Via Bonanno 6, 56126 Pisa, Italy.
Floridi
Monia
M
Giannaccini
Gino
G
Manetti
Fabrizio
F
Paparelli
Chiara
C
Strappaghetti
Giovannella
G
Botta
Maurizio
M
D000317:Adrenergic alpha-Antagonists / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism; D047309:Flavones; D005419:Flavonoids / Q000737:chemistry*; D006571:Heterocyclic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011485:Protein Binding; D011869:Radioligand Assay; D051381:Rats; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects* / Q000378:metabolism*; D044263:Receptors, Serotonin, 5-HT1 / Q000187:drug effects / Q000378:metabolism; D013329:Structure-Activity Relationship
D000317:Adrenergic alpha-Antagonists; D047309:Flavones; D005419:Flavonoids; D006571:Heterocyclic Compounds; D010879:Piperazines; D018340:Receptors, Adrenergic, alpha-1; D044263:Receptors, Serotonin, 5-HT1; C031503:phenylpiperazine; C043562:flavone