Design, synthesis, and alpha(1)-adrenoceptor binding properties of new arylpiperazine derivatives bearing a flavone nucleus as the terminal heterocyclic molecular portion

Laura Betti; Monia Floridi; Gino Giannaccini; Fabrizio Manetti; Chiara Paparelli; Giovannella Strappaghetti; Maurizio Botta

doi:10.1016/j.bmc.2003.12.033

Design, synthesis, and alpha(1)-adrenoceptor binding properties of new arylpiperazine derivatives bearing a flavone nucleus as the terminal heterocyclic molecular portion

Bioorg Med Chem. 2004 Mar 15;12(6):1527-35. doi: 10.1016/j.bmc.2003.12.033.

Authors

Laura Betti¹, Monia Floridi, Gino Giannaccini, Fabrizio Manetti, Chiara Paparelli, Giovannella Strappaghetti, Maurizio Botta

Affiliation

¹ Dipartimento di Psichiatria, Neurobiologia, Farmacologia e Biotecnologie, Università di Pisa, Via Bonanno 6, 56126 Pisa, Italy.

PMID: 15018926
DOI: 10.1016/j.bmc.2003.12.033

Abstract

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.

Publication types

Comparative Study
Research Support, Non-U.S. Gov't

MeSH terms

Adrenergic alpha-Antagonists / chemical synthesis*
Adrenergic alpha-Antagonists / chemistry
Adrenergic alpha-Antagonists / pharmacology
Animals
Cerebral Cortex / metabolism
Flavones
Flavonoids / chemistry*
Heterocyclic Compounds / chemical synthesis
Heterocyclic Compounds / chemistry
Heterocyclic Compounds / pharmacology
Piperazines / chemical synthesis*
Piperazines / chemistry
Piperazines / pharmacology
Protein Binding
Radioligand Assay
Rats
Receptors, Adrenergic, alpha-1 / drug effects*
Receptors, Adrenergic, alpha-1 / metabolism*
Receptors, Serotonin, 5-HT1 / drug effects
Receptors, Serotonin, 5-HT1 / metabolism
Structure-Activity Relationship

Substances

Adrenergic alpha-Antagonists
Flavones
Flavonoids
Heterocyclic Compounds
Piperazines
Receptors, Adrenergic, alpha-1
Receptors, Serotonin, 5-HT1
phenylpiperazine
flavone